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61+ Benefits of Probiotics

Written by Biljana Novkovic, PhD | Last updated:
Puya Yazdi
Medically reviewed by
Puya Yazdi, MD | Written by Biljana Novkovic, PhD | Last updated:
Probiotics

According to some researchers, probiotics have enormous potential to improve our GI tract, balance the immune system, fight infections and allergies, and improve our mood and cognitive function. What does the current science say? Read on to learn more.

What are Probiotics?

Gut Microbiota

At birth, the sterile human gut is immediately colonized with several types of microorganisms from both the mother and the environment. By the time they reach one year of age, each individual develops a unique bacterial profile [1].

It is estimated that only 10% of the cells in the human body actually belong to the body itself. The overwhelming majority of the cells consist of the diverse microbiota of nonpathogenic bacteria, 1-2 kg of them living in the gut alone [2].

Gut microbiota consists of at least 1014 bacteria [3], comprised of at least 160 different bacterial species from a pool of 1,000 – 1,150 [1].

Gut microbiota includes ~30 species of Bifidobacterium, 52 species of Lactobacillus, and others, such as Streptococcus and Enterococcus [4].

The genome of the entire gut microbiota named as “microbiome” exceeds the human nuclear genome by at least 100 times [3].

Human gut microorganisms are strongly involved in diverse metabolic, nutritional, physiological, and immunological processes [5]. They play an important role in energy homeostasis and through the microbe-gut-brain axis [3] by impacting our mood and cognitive abilities. They also stimulate the immune response, prevent pathogenic and opportunistic microbes/bacteria, and produce vitamins such as B and K [1].

Diet can exert a profound effect on the gut microbiota profile, and people in different parts of the world have different bacterial profiles [6]. For example, there is an association of Bacteroides and high animal fat or protein diets, while Prevotella is associated with a high carbohydrate diet [6].

Changes in microbiota composition can increases susceptibility to infections, immune disorders, inflammation, oxidative stress and insulin resistance [5].

Probiotics

Probiotic bacteria are live microorganisms known as “friendly gut bacteria” which when present and/or administered in adequate amounts can have potential health benefits [1].

The term “probiotic” comes from the Greek term ‘for life’ [5].

Probiotics have been regarded as beneficial since ancient times (particularly lactic acid bacteria – Lactobacilli and Bifidobacteria), but they came into the spotlight in the late 1800s and early 1900s, when it was proposed that consuming yogurt containing Lactobacillus would decrease toxin-producing bacteria in the gut and increase longevity [5].

Naturally occurring probiotic bacteria exist in fermented food products such as yogurt, kefir, sauerkraut, cabbage kimchee, and soybean-based miso and natto [1].

The most common probiotic strains belong to the species Lactobacillus and Bifidobacterium, followed by the genera Streptococcus, Enterococcus, Propionibacterium, Bacillus, and Escherichia. In addition, some yeast species are used as probiotics, for example, S. boulardii and S. cerevisiae [7, 1].

According to some studies, probiotics could potentially enhance the immune system, improve the skin’s function, enhance resistance against allergens, and decrease body pathogens [8].

They may also be anti-inflammatory, help improve blood lipid profile and glucose tolerance, and lower blood pressure and BMI. Note, however, that these benefits remain unproven [9, 10].

Note that in clinical studies, probiotic mixtures are often demonstrated to be better than a single strain for improving indigenous microflora [4].

Prebiotics

Prebiotics are specific carbohydrates, such as polysaccharides, fructans, and inulins, that can exert beneficial effects on the composition and metabolic activities of gut microorganisms. A diet high in inulin and related fibers, for example, has been shown to increase Bifidobacteria [1].

Synbiotics

A prebiotic and probiotic combination is referred to as a synbiotic when the net health benefit is synergistic [11].

Purported Health Benefits of Probiotics

Despite the promising evidence we discuss below, remember that the FDA has not yet approved probiotics for any condition or health claim. Take any single study – especially an animal or cell study – with a grain of salt, and remember to talk to your doctor before adding probiotics to your daily health plan.

1) Vitamin Levels

Daily consumption of L. acidophilus significantly improved vitamin B12 and folate levels in children [12].

Taking L. reuteri increased blood levels of vitamin D3 by 25.5% in a Canadian study [13].

L. reuteri isolated from sourdough has been shown to produce cobalamin (vitamin B12) [14], while L. plantarum isolated from raw cow milk can produce riboflavin (B2) and folate (B9) [15].

Folate-rich fermented milk produced by high-folate-producing S. thermophilus increases hemoglobin levels in mice [16].

L. cerevisiae is also a rich dietary source of folate [17, 18].

2) Iron Levels

Iron deficiency in young women in south India was associated with low levels of Lactobacilli [19].

L. plantarum was also associated with increased iron absorption by women: from a fruit drink by approximately 50% [20] and from an oat base by over 100% [21].

Preschool children supplemented with L. acidophilus exhibited higher red blood cell status [22], and a significant reduction in the prevalence of anemia [12].

Milk with B. animalis ssp. lactis and prebiotic oligosaccharides reduced the risk of anemia and iron deficiency by 45% and increased weight gain by 0.13 kg/year in 1-4-year-old children [23].

3) Minerals

L. helveticus increased blood calcium levels in elderly volunteers [24], and postmenopausal women [25].

L. fermentum may increase the bioavailability of calcium, phosphorus, and zinc in fermented goat milk [26], while fermented milk containing L. plantarum showed higher calcium retention [27].

By degrading phytate, S. cerevisiae may improve the absorption of iron, zinc, magnesium, and phosphorus [17, 28].

4) Antioxidant Action

L. casei, L. helveticus, L. fermentum, B. bifidum and B. subtilis exhibit antioxidant properties [29, 30, 31, 32, 33, 34].

Similarly, B. animalis and L. lactis effectively scavenge free radicals and significantly enhance the activities of antioxidative enzymes in mice [35, 36].

A B. subtilis signal molecule induces the heat shock protein Hsp27 in mammalian cells; this protein protects intestinal cells against oxidant-mediated tissue damage [37].

5) Neuroprotection

B. breve and C. butyricum increase BDNF in rats and mice, respectively [38].

C. butyricum, furthermore, restores butyrate in the brain, reduces neuronal cell death, and significantly attenuates cognitive dysfunction and histopathological changes in mice with vascular dementia [39].

C. butyricum also exerts neuroprotective effects against ischemia/reperfusion injury in mice [40] and attenuates cognitive impairment, cell damage and neuronal death in diabetic mice with cerebral ischemia/reperfusion injury [41].

6) Cognitive Function

Gut probiotics play a major role in the bidirectional communication between the gut and the brain [8], referred to as the “microbiota-gut-brain” axis. It is now generally accepted that microbiota can affect behavior and modulate cognitive function [6].

According to animal studies, some probiotics may improve both spatial and non-spatial memory [42]. The administration of probiotics considerably improved the impaired spatial memory and efficiently reversed deteriorated brain in diabetic rats [43, 6].

Germ-free mice display deficits in non-spatial and working memory. Also, mice that were exposed to gut bacterial infection and stress exhibited memory deficits, while probiotic treatment 7 days before and during the infection prevented cognitive dysfunction [6].

B. longum improved learning and memory [44], while L. helveticus improved scopolamine-induced cognitive impairments and object recognition memory [45] in mice.

L. helveticus also improved stress-induced cognitive dysfunction [46] and restored cognitive function in rats with neuroinflammation [47].

L. plantarum improved learning and memory in rats with vascular dementia, by acting as a blood pressure-lowering and neuroprotective agent [48].

Finally, L. casei potentiated the effect of proanthocyanidins extracted from lotus seedpod and ameliorated memory impairments in mice [49].

7) Mood

The vast number of microorganisms in our intestines may have a major impact on our state of mind [8]. Gut microorganisms are able to produce and deliver such neuroactive substances as serotonin and gamma-aminobutyric acid (GABA) [8].

A multispecies probiotic containing B. bifidum, B. lactis, L. acidophilus, L. brevis, L. casei, L. salivarius, and L. lactis reduced negative thoughts in non-depressed individuals [50].

One study found an inverse association between constipation and feelings of calmness, elatedness, and agreeableness, i.e. frequent constipation was associated with a poorer mood state. A probiotic multivitamin compound significantly improved the general condition of participants, with a 41% improvement in stress, a 29% decrease in the prevalence of infection and a 91% reduction in GI discomfort [1].

In another study, probiotic yogurt improved the mood of those with an initially poor mood [8].

Consuming a probiotic yogurt or a multispecies probiotic capsule for six weeks had beneficial effects on the mental health biomarkers of petrochemical workers [8].

8) Depression

One study found a correlation between human microbiota and depression. Probiotics significantly decreased depression scores in both healthy individuals and patients with major depressive disorder under 60 years of age [8].

L. helveticus and B. longum reduced depression in healthy volunteers who regularly took these probiotics [8].

A mix of L. acidophilus, L. casei and B. bifidum decreased depression, and in addition lowered insulin levels, insulin resistance, and hs-CRP, and increased glutathione levels in patients with major depressive disorder [51].

B. infantis, L. helveticus and L. rhamnosus each improved symptoms of depression in rats [8, 46].

Chronic administration of B. infantis appears to protect rats from depressive symptoms caused by stress induced through maternal separation [52].

9) Anxiety

Infecting healthy mice with pathogenic bacteria stimulates anxiety behaviors within hours of infection suggesting that changes in the gut microbiota can very quickly induce biochemical changes in the brain [1].

L. helveticus and B. longum decreased anxiety and anger/hostility in human volunteers [53].

Probiotic treatment with L. helveticus improved anxiety-like behavior in rats [46, 47], and prevented the negative effect of Western-style diet on anxiety and memory in mice [54].

L. rhamnosus [6], L. fermentum [55] and B. longum [56] also reduce anxiety-like behavior in mice.

Chronic ingestion of L. plantarum reduced anxiety-like behaviors in mice, and increased dopamine, and serotonin levels [57, 58].

10) OCD

L. rhamnosus treatment attenuates mouse OCD-like behaviors [59].

11) Autism

There is a potential role for intestinal microorganisms in the complex pathophysiology of autism spectrum disorder (ASD). Treatment of an autism mouse model with probiotics ameliorated ASD-related traits [6].

In an animal model of social deficits in offspring, L. reuteri was found to be 9X lower. Supplementing with it increased oxytocin levels and significantly improved sociability and preference for social novelty in mice offspring [60].

12) Schizophrenia

Daily administration of B. longum reduced signs and symptoms of a model of schizophrenia in mice, decreased the resting level of plasma corticosterone and the ratio of kynurenine to tryptophan [61].

13) Stress and Seasonal Illnesses

L. casei lowered academic-stress-induced increases in cortisol and the incidence of physical symptoms in student volunteers [62].

In stressed rats, L. casei suppressed blood corticosterone levels [62].

Similarly, when L. casei was administered to medical students undertaking an authorized nationwide examination to test their response to stress, this bacterium increased serotonin levels, lowered the rate of subjects experiencing common abdominal and cold symptoms, and decreased the total number of days students experienced these symptoms [63].

In academically stressed undergraduate students, B. bifidum increased the proportion of healthy days per participant and decreased the percentage of participants reporting cold/flu during the intervention period [64].

Similarly, B. bifidum reduced self-reported stress and stress associated diarrhea/GI discomfort in undergraduate students [65].

14) Sleep-Wake Cycle

L. helveticus-fermented milk significantly improved sleep efficiency in healthy elderly people [66].

In volunteers with insomnia, L. brevis showed a mildly beneficial effect on sleep in subjects with insomnia [67].

Daily voluntary wheel-running and sleep rhythmicity became intensified in mice when heat-killed L. brevis was added to the diet [68].

15) Weight Loss

According to a few studies, consuming probiotics may reduce body weight and BMI. A greater effect is achieved in overweight subjects, when multiple species of probiotics are consumed in combination or when they are taken for more than 8 weeks [69].

L. rhamnosus induced weight loss in women, reducing fat mass and circulating leptin concentrations [70].

L. gasseri significantly decreased body weight and visceral and subcutaneous fat in adults with a tendency toward obesity [71].

Despite there being no change in behavior or diet, the administration of L. gasseri modestly reduced weight and waist and hip circumference in obese and overweight adults [72].

L. gasseri significantly decreased BMI, abdominal visceral fat, waist and hip circumferences, and body fat mass in healthy Japanese adults. However, constant consumption of this probiotic may be required to maintain this effect [73].

Both L. rhamnosus and L. gasseri also significantly lowered weight in mice [74, 75, 76] while L. gasseri was also shown to reduce body weight in rats [77].

16) Obesity

Intestinal microbiota can affect host adiposity and regulate fat storage [5].

Bifidobacteria content was higher in children of normal weight than those who were showing signs of becoming overweight [1]. Similarly, the presence of B. animalis was found to be negatively associated with BMI in humans [78, 79].

The intake of synbiotics (probiotics + prebiotics) in obese children resulted in a significant reduction in BMI, waist circumference, and some cardiometabolic risk factors, such as TC, LDL-C, and TAG [11].

L. acidophilus, B. animalis ssp. lactis and L. casei reduced BMI, fat percentage, and leptin levels in overweight individuals [11].

Daily ingestion of milk containing B. animalis ssp. lactis significantly reduced the BMI, total cholesterol, low-density lipoprotein, and inflammatory markers in humans [80].

A low-calorie diet supplemented with L. plantarum reduced BMI in Russian adults with obesity and hypertension [11].

L. gasseri prevented abdominal fat accumulation [81] and decreased body weight in adults with obese tendencies [71].

B. breve lowered fat mass and improved GGT and hs-CRP in adults with obese tendencies [82].

L. rhamnosus improved markers of liver health in obese children with liver dysfunction noncompliant with lifestyle interventions [83].

L. paracasei decreases caloric intake in both human and animal subjects [84].

Oral administration of B. longum, B. bifidum, B. infantis, and B. animalis decreased glucose levels, ameliorated insulin resistance and reduced the expressions of inflammatory adipocytokines in obese mice [85].

B. breve reduced body weight gain and accumulation of visceral fat in a dose-dependent manner, and improved serum levels of total cholesterol, fasting glucose, and insulin in a mouse model of diet-induced obesity [86].

C. butyricum reduced fat accumulation in liver and blood, lowered insulin levels and improved glucose tolerance and insulin sensitivity in obese mice. Furthermore, C. butyricum administration ameliorated GI and fat tissue inflammation [87].

Water extract of L. paracasei reduced body weight in obese rats. It decreased the formation of lipid plaques in the aorta, reduced fat cell size and inhibited fat absorption, thereby reducing fat production (lipogenesis) [88].

NOTE: Although some studies show beneficial effects of L. reuteri in obesity-related symptoms, in one study, this species was more abundant in obese people than in people of healthy weight [89].

17) Blood Glucose & Insulin Sensitivity

Several studies suggest that probiotics may have a significant effect on lowering fasting blood glucose and insulin in diabetics [90, 91].

L. plantarum reduced glucose levels in postmenopausal women [11].

L. casei improved insulin sensitivity in subjects with metabolic syndrome [11].

Furthermore, long‐term ingestion of L. casei reduced insulin resistance and glucose intolerance in rats fed a high‐fat diet [92], rats with hyperinsulinemia [93], and obese mice [92].

L. plantarum significantly reduced blood glucose levels in response to insulin in mice on a high-fat diet [94].

An L. paracasei probiotic was shown to improve many aspects of insulin resistance, such as fasting response, hormonal homeostasis, and glycemic control in rats [95].

gasseri increased energy expenditure, reduced blood glucose, improved glucose tolerance, attenuated inflammation [96], and reduced insulin levels in rats [97].

18) Diabetes

Many researchers believe that the gut microbiota play an important role in the pathogenesis and metabolic disturbances of type 2 diabetes mellitus (T2DM) [3].

Gut microbiota of adults with T2DM is quite different from the microbiota of nondiabetic adults. The content of Bifidobacteria is decreased, whereas Enterococci and Escherichia coli are increased significantly [3].

Probiotics may improve carbohydrate metabolism, total cholesterol, fasting blood glucose, insulin sensitivity, and antioxidant status and reduce metabolic stress in subjects with T2DM [3, 11].

Certain probiotics (L. lactis, Bifidobacteria) secrete an insulin analog [5], and they can modestly improve fasting insulin in people with T2DM [98].

In Humans:

In T2DM patients, L. acidophilus and B. animalis increased good cholesterol (HDL-C) levels and decrease the LDL-C/HDL-C ratio [11]. They further significantly decreased fasting blood glucose and exerted antioxidant effects [11].

A synbiotic containing L. acidophilus, L. casei, B. bifidum, and inulin decreased fasting plasma glucose, blood insulin concentrations and increased insulin sensitivity in overweight diabetic patients with coronary heart disease. In addition, HDL-cholesterol levels were increased [99].

Consumption of a synbiotic containing B. coagulans reduced insulin levels, improved blood lipid profile and increased good cholesterol (HDL-C) in type 2 diabetes (T2D) patients [11, 100, 101].

Similarly, consumption of a synbiotic with B. coagulans improved NO, MDA [102], hs-CRP, uric acid, and plasma total GSH levels in diabetic patients [103].

L. acidophilus preserved insulin sensitivity in men with T2DM [11].

Soy milk containing L. plantarum has antioxidative properties and decreases DNA damage in patients with T2DM [11].

Diabetic patients who develop foot ulcers are at more risk of dying prematurely than those without the complication. B. subtilis shows antimicrobial activity against four diabetic foot ulcer bacterial pathogens [104].

Animal studies:

B. animalis ssp. lactis reduces weight gain and fat mass, improves glucose tolerance [105], decreases fasting insulin and blood glucose, and significantly improves insulin tolerance in mice with diabetes [106].

B. bifidum decreased fasting blood glucose and insulin in diabetic rats [107].

B. bifidum stabilized blood sugar, lower cholesterol levels in serum, and improve metabolic activity in mice [108].

L. brevis decreased glucose levels in diabetic rats [109].

L. gasseri decreased blood glucose and improved glucose sensitivity in diabetic mice [110].

johnsonii inhibits hyperglycemia, reduced the elevation of blood glucose and glucagon levels in diabetic rats [111], and inhibited insulin resistance in mice [112].

Administration of L. casei and B. bifidum alone and in combination ameliorated hyperglycemia, dyslipidemia, and oxidative stress in diabetic rats [107].

L. casei significantly improved glucose intolerance, dyslipidemia, immune-regulatory properties, and oxidative stress in mice with T2D [113].

Treating diabetic mice with nonviable L. salivarius reversed gut microbial imbalance, restored mucosal antibacterial protein and lessened endotoxin levels [114].

L. rhamnosus exerted an anti-diabetic effect in mice, with an anti-hyperglycemic effect in several rodent models. L. rhamnosus further improves glucose tolerance and enhances insulin sensitivity [115].

Treatment with L. plantarum improved blood glucose, hormones, and lipid metabolism in diabetic rats [116].

19) Bad Cholesterol

Daily consumption of yogurt containing L. acidophilus after each dinner contributes to a significant reduction in cholesterol [5]. However, in another study of men and women with normal to borderline high cholesterol, L. acidophilus did not lower blood cholesterol [117].

A synbiotic product containing L. gasseri and inulin reduced total blood cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides in hypercholesterolemic men and women [118].

Buffalo milk yogurt and soymilk yogurt with B. longum decreased total cholesterol by 50%, LDL- cholesterol by 56%, and triglycerides by 51% [5].

In one study, L. reuteri reduced LDL cholesterol by 11.64%, reduced total cholesterol by 9.14%, non-HDL-cholesterol by 11.30% and apoB-100 by 8.41% [119]. In another study, L. reuteri reduced LDL by 8.92% and total cholesterol by 4.81% [120].

6-week supplementation of L. salivarius along with fructooligosaccharide (FOS) significantly reduced total cholesterol, “bad” (LDL) cholesterol, and triglycerides [121].

B. longum reduced total cholesterol, particularly among subjects with moderate hypercholesterolemia [122].

L. fermentum modestly improved cholesterol levels in a clinical study [123].

A synbiotic containing B. coagulans reduced TAG and VLDL in pregnant women [124], and reduced total blood cholesterol, LDL-cholesterol in a small clinical trial [125, 126].

In another study, a combination of bacteria strains more effectively reduced total cholesterol and liver cholesterol compared to individual bacteria strains [5].

B. animalis, B. bifidum, and B. longum reduced total cholesterol and LDL-C in children with primary dyslipidemia [127].

Milk fermented with L. acidophilus and B. longum significantly reduced LDL cholesterol in hypercholesterolemic women [128].

In overweight subjects, the administration of capsules with Bifidobacteria, Lactobacilli, and S. thermophilus significantly improved lipid profiles, reducing total cholesterol (TC), triacylglycerols (TAG), and LDL-C levels [11].

20) Good Cholesterol

According to some researchers, probiotics may increase high-density lipoprotein-cholesterol (HDL-C) [3].

In T2DM patients, L. acidophilus and B. animalis increased good cholesterol (HDL-C) levels [11].

A synbiotic containing L. acidophilus, L. casei, B. bifidum, and inulin increased HDL-cholesterol in diabetic subjects [99].

A synbiotic shake containing L. acidophilus, B. bifidum and fructo-oligosaccharides significantly increased HDL-C in elderly people with diabetes [11].

6-week supplementation of L. salivarius along with fructooligosaccharide (FOS) significantly increased “good” (HDL) cholesterol in healthy young volunteers [121].

In overweight subjects, Bifidobacteria, Lactobacilli, and S. thermophilus significantly improved HDL-C [11].

B. coagulans increased good cholesterol in diabetic patients [11].

L. plantarum increased “good” (HDL) cholesterol in mice [129].

B. bifidum increased HDL in diabetic rats [107].

21) Blood Pressure

L. helveticus produces angiotensin-converting enzyme (ACE)-inhibitory peptides that could potentially prevent or control high blood pressure [130].

L. helveticus fermented milk lowered blood pressure in hypertensive subjects [131, 132].

Daily ingestion of the tablets containing powdered fermented milk with L. helveticus in subjects with high-normal blood pressure or mild hypertension reduced elevated blood pressure without any adverse effects [133].

Long-term treatment with L. helveticus-fermented milk reduced arterial stiffness in hypertensive subjects [134].

L. plantarum reduced blood pressure in Russian adults with obesity [11].

L. faecium and S. thermophilus reduced systolic blood pressure in overweight and obese subjects [11].

L. plantarum [48, 135], L. johnsonii [136] and L. lactis [137, 138] acted as a blood pressure-lowering agent in rats.

22) Metabolic Syndrome

B. animalis ssp. lactis significantly reduced BMI, total cholesterol, low-density lipoprotein and inflammatory cytokines in patients with metabolic syndrome [139].

L. plantarum reduced total cholesterol, LDL-cholesterol, glucose and homocysteine levels in postmenopausal women with metabolic syndrome [140].

L. casei improved insulin sensitivity in subjects with metabolic syndrome [11].

L. gasseri decreased food and energy intake, and improved body weight, insulin resistance and cholesterol levels in rats with metabolic syndrome (MS) [141].

23) Cardiovascular Disease

According to some researchers, probiotics and prebiotics may help prevent and reduce the severity of cardiovascular disease due to a reduction in total serum cholesterol, low-density lipoprotein (LDL-cholesterol), and inflammation [5].

Daily supplementation with S. boulardii lowered remnant lipoprotein in hypercholesterolemic adults, a predictive biomarker and potential therapeutic target in the treatment and prevention of coronary artery disease [142].

In a human trial, L. casei improved insulin sensitivity, an important risk factor for cardiovascular morbidity, especially stroke and coronary heart disease and mortality [11].

L. acidophilus consumption led to a 2.4% to 3.2% reduction in blood cholesterol in clinical studies. Since every 1% reduction in serum cholesterol concentration is associated with an estimated 2% to 3% reduction in risk for coronary heart disease, some researchers believe that regular intake of L. acidophilus has the potential to reduce the risk for coronary heart disease by 6 to 10% [143].

L. acidophilus may protect against atherosclerosis through the inhibition of intestinal cholesterol absorption in mice fed a Western diet [144].

Lipoteichoic acid (LTA) from L. plantarum inhibited the production of proinflammatory cytokines and suppressed atherosclerotic plaque inflammation in mice [145].

L. acidophilus reduced cholesterol and inhibited the accumulation of lipoprotein in atherosclerotic plaques in mice [146].

L. acidophilus attenuated the development of atherosclerotic lesions in mice, possibly by reducing oxidative stress and inflammatory responses [147].

24) Gut Health

Probiotics can decrease the number of potentially pathogenic gastrointestinal microorganisms and pathogens, reduce gastrointestinal discomfort, flatulence and bloating, and improve bowel regularity [8].

B. animalis spp. lactis improved digestive comfort and GI symptoms in healthy adults [148, 149].

Probiotic fermented milk containing B. animalis spp. lactis by healthy women may improve GI well-being and decrease the frequency of GI symptoms [150, 151, 152].

4 weeks’ supplementation with B. animalis ssp. lactis resulted in a clinically relevant benefit on defecation frequency in healthy adults with abdominal discomfort [153].

Ingestion of B. bifidum significantly decreased the prevalence of gastric and lower abdominal symptoms in adults taking no medication [154].

Administration of L. helveticus to healthy human subjects resulted in a significant increase in butyrate, beneficial for gut homeostasis [155].

Probiotics promoted gastric mucus secretion [4] and B. bifidum alleviated acute gastric injury by enhancing the production of gastric mucin in rats [156].

Modifying Gut Microbiota

Probiotics, in general, tend to increase the levels of Lactobacilli and Bifidobacteria in the gut, while decreasing the levels of potentially pathogenic microorganisms [157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169].

Strengthening the Intestinal Barrier

The intestinal barrier separates the contents of the gut from the rest of the body. This barrier prevents the entry of harmful substances such as foreign antigens, toxins, and microorganisms. Hyperpermeability of this barrier (“leaky gut”) may contribute to the pathogenesis of several gastrointestinal disorders including IBD, Celiac disease, and food allergy [170].

In humans, L. rhamnosus protected against disruption of the gastric mucosal barrier [4].

Fermented milk with L. paracasei promoted intestinal epithelial cell growth and intestinal epithelial integrity and strengthened the intestinal barrier against chemical and inflammatory stimuli-induced damage [171].

L. paracasei synbiotic therapy may prevent or repair colon damage in mice with acute colitis, where this bacterium completely restored epithelial barrier integrity [172, 173].

In rats, B. bifidum or B. animalis protected the mucous membrane layer of the stomach [4].

S. cerevisiae strengthened epithelial barrier function [174]. Oral treatment with viable or heat-killed S. cerevisiae strain prevented bacterial translocation, protects intestinal barrier integrity, and stimulated immunity in mice with intestinal obstruction [175].

Drug-Induced GI Damage

Probiotics maintained healthy intestinal microbiota in subjects receiving antibiotic treatment [8].

L. acidophilus administered with amoxicillin/clavulanate was associated with a significant decrease in patient complaints of GI side effects and yeast superinfection [176].

L. casei is effective for the treatment of aspirin-associated small bowel injury in chronic low-dose aspirin users [177].

Long-term L. rhamnosus supplementation influenced the composition of the intestinal microbiota in children and reduced the frequency of gastrointestinal complaints after antibiotic use, preventing certain bacterial infections for up to 3 years after the trial [178].

L. delbrueckii microcapsules relieved intestinal tissue damage in mice and improved antibiotic-induced intestinal microbiota dysfunction [179].

L. paracasei therapy prevented antibiotic induced visceral hypersensitivity and restored normal gut permeability in rats [180].

L. fermentum normalized the composition of gut microbiota and alleviated ampicillin-induced inflammation in the colon in mice [55].

B. animalis ssp. lactis protected against NSAID-induced GI side effects in rats and may prevent more serious GI mucosal damage and/or enhance the recovery rate of the stomach mucosa [181].

S. boulardii significantly reduced the numbers of gastric ulcers and the ulceration surface of the gastric mucosa in rats treated with ibuprofen [182].

S. thermophilus reduced inflammation and prevented chronic gastritis in aspirin-treated mice [183, 184].

Gastric Ulcers

Probiotics inhibited the development of acute gastric mucosal lesions and accelerated gastric ulcer healing [4].

Lactobacilli promoted gastric ulcer healing in rats when administered as an individual probiotic strain, such as L. rhamnosus, L. gasseri, or L. acidophilus or as a probiotic mixture [4, 4, 4, 185, 186, 4].

B. breve and B. bifidum repaired and protected the mucosa of rats against gastric ulcers and erosions [4].

Pretreatment of mice with gastric ulcers with the probiotic C. butyricum alleviated the inflammation and gastric mucosal damage [4].

Certain yeasts, such as S. boulardii and S. cerevisiae have also shown beneficial effects in rats with gastric ulcers [4].

Diarrhea

Use of probiotics in antibiotic-associated diarrhea decreased the risk of diarrhea by 52%, traveler’s diarrhea by 8%, and acute diarrhea from various causes by 34%. Probiotics were more effective in reducing the risk of acute diarrhea in children 57% versus 26% in adults [187].

Acute Infective Diarrhea:

L. casei reduced the incidence, duration, and severity of diarrhea in children [188, 189].

L. paracasei effectively resolved acute diarrhea [190] and ameliorated non-rotavirus-induced diarrhea in children [191].

L. acidophilus reduced the duration of diarrhea in hospitalized, but not outpatient, children [192], and ameliorated both rotavirus-positive diarrhea [193] and rotavirus-negative diarrhea in children [194].

L. acidophilus and B. bifidum shortened the duration of diarrhea in infants and children [195].

L. rhamnosus administration was associated with significantly lower rates of and symptomatic rotavirus gastroenteritis diarrhea in hospitalized children [196].

L. reuteri decreased the incidence of diarrhea in children [197].

Formula supplemented with B. bifidum and S. thermophilus reduced the incidence of acute diarrhea and rotavirus shedding in infants admitted to hospital [198].

B. breve together with S. thermophilus reduced the severity of acute diarrhea and dehydration among healthy young infants [199].

B. animalis spp. lactis milk formula prevents diarrhea in infants and decreased diarrhea frequency and duration [200, 201, 202].

S. boulardii significantly reduced the frequency and duration of acute diarrhea in children [203, 204, 205, 206, 207, 208, 209, 210]. It also often reduced the length of ECU and hospital stay in acute infectious gastroenteritis in children [211, 212].

S. boulardii also decreased the duration and frequency of diarrhea and ameliorated abdominal pain in adults [213]; it shortened the length of hospital stay in patients with acute infectious diarrhea [214].

Antibiotic-Associated Diarrhea:

Treatment with L. rhamnosus reduced the risk of antibiotic-associated diarrhea (AAD) in patients treated with antibiotics from 22.4% to 12.3% [215].

L. casei intake was associated with a decreased risk of antibiotic-associated diarrhea [216, 217].

L. helveticus and L. rhamnosus supplementation significantly reduced the duration of antibiotic-associated diarrhea in healthy adults receiving antibiotics [218].

B. animalis spp. lactis together with S. thermophilus reduced the frequency of antibiotic-associated diarrhea (AAD) in infants [219].

Concomitant administration of C. butyricum with antibiotics normalized the intestinal microbiota, prevented the decrease of Bifidobacteria, and effectively prevented and improved antibiotic-associated diarrhea in children [220].

Some studies report that S. boulardii is not effective in preventing the development of antibiotic-associated diarrhea [221, 222, 223, 224]. However, many studies demonstrate that S. boulardii effectively reduced the risk of antibiotic-associated diarrhea in both children and adults [225, 226, 227, 228, 229, 230, 231].

B. subtilis significantly reduced the incidence of antibiotic-associated diarrhea and prevented nausea, bloating, vomiting and abdominal pain [232].

Traveler’s Diarrhea:

S. boulardii may prevent traveler’s diarrhea, particularly in regions such as North Africa and in the Near-east [233].

Chemo- and Radiotherapy-induced Diarrhea:

Probiotics may have a beneficial effect on the prevention of chemo- and radiotherapy-induced diarrhea, where they rarely cause adverse effects [234].

See individual probiotic posts for more information and animal studies.

Constipation

L. paracasei relieved constipation [235].

Heat-killed L. brevis improved intestinal function in women with constipation [236, 237].

L. reuteri improved constipation, increasing the number of bowel movements in adults [238] and infants [239].

B. breve effectively diminished abdominal pain and increased stool frequency in children with functional constipation [240].

B. animalis spp. lactis showed beneficial effects on constipation in human studies [241, 242, 243].

B. coagulans improved constipation symptoms in children [244] and adults [245].

P. freudenreichii relieved constipation in young healthy women [246].

Some researchers believe that a synbiotic regimen of lactulose and live binary B. subtilis could be an effective and safe therapy for elderly with functional constipation [247].

See individual probiotic posts for more information and animal studies.

Irritable Bowel Syndrome

Irritable bowel syndrome appears to cause a reduction in intestinal Lactobacilli and Bifidobacteria [1]. Probiotics improved global IBS symptoms and decrease IBS-associated pain [187].

L. acidophilus reduced abdominal pain and discomfort in patients with irritable bowel syndrome (IBS) [248, 249].

L. plantarum reduced gas problems and pain in people who suffer from irritable bowel syndrome [20].

Probiotics containing L. plantarum and B. breve in IBS patients decreased pain by 38% in the probiotic group compared with 18% in the placebo group. After 28 days, the pain was decreased by 52% in the probiotic group compared with 11% in the placebo group [187].

L. rhamnosus may reduce pain frequency and intensity in children [250] and adults [251] with IBS.

L. rhamnosus may also reduce symptoms in children with functional gastrointestinal disorders [251].

According to one study, L. reuteri may help produce serotonin and lessen susceptibility to gut problems and IBS [252].

L. rhamnosus, L. reuteri and VSL#3 significantly increased treatment success for functional gastrointestinal disorders (FGIDs) in children and adolescents [253].

A mixture of B. infantis, B. breve, and B. longum improve abdominal pain and the quality of life in children with irritable bowel syndrome (IBS) [254].

B. longum ssp. infantis reduced intestinal inflammation and improved abdominal pain/discomfort, bloating/distention, and bowel movement difficulty in patients with IBS [8, 255, 256].

B. bifidum significantly improved reported pain/discomfort, distension/bloating, urgency and digestive disorder in patients with IBS [257].

In one study, fermented milk containing B. bifidum improved symptoms in patients with functional gastrointestinal disorders (FGID). Abdominal pain, diarrhea, and constipation significantly improved, as did acid-related dyspepsia. Psychological symptoms such as anger and hostility also improved [258].

B. animalis had a beneficial effect on discomfort, bloating and constipation in constipation-predominant IBS patients [259].

B. animalis spp. lactis significantly improved objectively measured abdominal girth and gastrointestinal transit, as well as reduced symptomatology in IBS patients [260].

B. coagulans decreased bloating, vomiting, diarrhea, abdominal pain, and stool frequency and increased the quality of life in patients with diarrhea-predominant irritable bowel syndrome (IBS) [261, 262, 263, 264].

A combination of simethicone and B. coagulans reduced bloating and discomfort in patients with IBS [265].

L. brevis improved the quality of life, reduced diarrhea and abdominal pain, and increased Bifidobacteria in patients with IBS [266].

S. boulardii improved the cytokine profile, histology, and the quality of life of patients with diarrhea dominant irritable bowel syndrome (IBS-D) [267] or mixed-type IBS [268].

S. boulardii alone or with mesalazine improved IBS-D symptoms [269]. One study, however, found no improvement in IBS-D patients after S. boulardii treatment [270].

In one clinical trial, S. cerevisiae reduced abdominal pain and discomfort in subjects with IBS [271]. In another trial, however, S. cerevisiae had no beneficial effect on IBS symptoms and wellbeing. However, it seemed to have some effect in the subgroup with constipation [272].

A combination product designated VSL#3, which contains large quantities of 8 bacterial species, was shown to significantly improve IBS symptoms [187].

Inflammatory Bowel Disease

B. longum ameliorated ulcerative colitis symptoms in Japanese patients [273].

S. boulardii added to baseline therapy improved intestinal permeability in Crohn’s disease (CD) patients, even though complete normalization was not achieved [274]. This probiotic also reduced the frequency of bowel movements in CD patients [275].

P. freudenreichii was effective against mild to moderate ulcerative colitis in a human pilot study [276].

In Asian studies involving patients with ulcerative colitis, the addition of a B. subtilis probiotic significantly reduced the number of days with bloody stool, led to complete remission without relapse, and significantly increased the efficacy of mesalazine or sulfasalazine therapy [277].

S. plantarum ameliorated ulcerative colitis in mice via both anti-inflammatory and immunomodulatory activities [278] and decreased the severity of intestinal inflammation in mice with inflammatory bowel disease (IBD) [188].

B. bifidum decreased symptoms of inflammatory bowel disease (IBD) in mice, such as thickened intestinal wall and inflammatory cell infiltration, and decreased inflammatory cytokine production [279].

Other probiotics that were effective in ameliorating colitis in animal models include L. casei [280, 281], L. paracasei [282], L. salivarius [283], L. delbrueckii ssp. bulgaricus [284], L. delbrueckii ssp. lactis [285], L. helveticus [286], B. longum [287], B. animalis ssp. lactis [288, 289, 290], C. butyricum [291, 292, 293], B. coagulans [294, 295], L. brevis [296, 297, 298], L. fermentum [299, 300, 301, 302], S. boulardii [303], L. lactis [304, 305, 306, 307], S. thermophilus [308], P. freudenreichii [164, 309, 310], B. subtilis [311, 312, 313, 314] and S. cerevisiae [315, 316].

B. longum ssp. infantis ameliorated colitis, possibly by decreasing Th1 and Th17 responses [317].

S. thermophilus also repressed the Th17 response to ameliorate intestinal lesions [318].

S. boulardii treatment limited the infiltration of Th1 cells into the inflamed colon and inhibited proinflammatory cytokine production in mice with IBD [319].

Note that L. crispatus may ameliorate colitis in mice [320]; however, a specific strain, M206119, exacerbated intestinal inflammation [321].

Check individual probiotic posts for more information.

Necrotizing Enterocolitis

Oral supplementation of L. paracasei reduced the clinical progression of necrotizing enterocolitis in infants [322].

Prophylactic L. acidophilus and B. infantis reduced the incidence and mortality of necrotizing enterocolitis (NEC) in infants [323].

B. breve was associated with decreased risk of necrotizing enterocolitis in neonates [324].

Oral administration of B. breve reduced the production of butyric acid in infants, which may be helpful in protecting low birth weight infants from digestive diseases such as necrotizing enterocolitis [325].

However, one study found no benefit in B. breve administration for the prevention of necrotizing enterocolitis and late-onset sepsis in very preterm infants [326].

B. breve suppressed inflammation, reduces the pathology and increases survival in rats with necrotizing enterocolitis [327].

Diverticular Disease

L. paracasei, in association with a high-fiber diet, effectively reduced abdominal bloating and prolonged abdominal pain in patients with symptomatic uncomplicated diverticular disease [328].

25) Immunity

Gut microbiota cooperate with the host immune system through an extensive array of signaling pathways [5].

Studies with germ-free animals show that the microbiota are necessary for the development and regulation of immunity in the gut, where it prevents the development of inappropriate inflammation [329].

According to some researchers, probiotics may modify the immune system by stimulating anti-inflammatory cytokines, downregulating proinflammatory cytokines, and modulating white blood cell responses [4].

Probiotics activated both innate and acquired immunity in humans [330, 189, 331, 332, 333, 334, 335, 336, 337, 338, 339].

L. paracasei, L. delbrueckii, L. fermentum, L. lactis, L. gasseri, B. longum, B. breve, B. animalis and other probiotics were shown to skew the Th1/Th2 balance toward Th1 [340, 341, 342, 343, 344, 345, 346, 347, 348, 349] in infections and allergies.

Against Infections

L. paracasei prevented common infectious disease in children attending daycare [350].

L. helveticus supplementation significantly shortened the duration and decreased the number of symptoms of upper respiratory tract illness in athletes and increased their sense of vigor [351].

Fermented milk containing L. johnsonii suppressed infections in the elderly [352].

L. brevis reduced the incidence of influenza in elementary schoolchildren. The improvement was especially pronounced in unvaccinated individuals [353].

S. boulardii enhanced the immune response in pediatric acute gastroenteritis [354].

Yogurt fermented with L. lactis lowered the risk of the common cold in human subjects [355].

Fermented milk containing L. rhamnosus significantly reduced the risk of respiratory tract infections that lasted longer than three days in hospitalized children [250].

Preterm infants treated daily with L. rhamnosus in capsules, starting within one week after birth, had a significantly lower incidence of respiratory tract infections (RTIs) and rhinovirus-induced episodes in the first 2 months [250].

Consumption of L. rhamnosus reduced the occurrence of respiratory illness in children attending daycare centers [356].

Children receiving L. rhamnosus probiotics had fewer days with respiratory symptoms per month than the children in the control group [357].

Capsulated L. rhamnosus appeared to protect hospitalized patients against ventilator-associated pneumonia, mainly when caused by Gram-negative pathogens like Pseudomonas aeruginosa [250].

In cystic fibrosis patients with P. aeruginosa, long-term L. rhamnosus significantly decreased the incidence of pulmonary exacerbations and increased body weight [250].

L. casei significantly lowered the incidence and duration of upper respiratory tract infections (URTIs) in healthy middle-aged office workers [358].

Similarly, in healthy shift workers, L. casei decreased the incidence of gastrointestinal and respiratory common infectious disease (CIDs), increased the time to the first occurrence of CID, and reduced the total number of CIDs in the subgroup of smokers. In the course of CID, the total duration of fever was lower and an increase in leukocyte, neutrophil, and natural killer (NK) cell counts and activity was observed [359].

L. casei also lowered the incidence of common infectious diseases (CIDs) in children [360], decreased the duration of CID, and especially upper-respiratory-tract infections (URTI) such as rhinopharyngitis in the elderly [361].

In athletic men and women who engaged in endurance-based physical activities in winter, L. casei lowered the proportion of subjects who experienced 1 or more weeks with upper-respiratory-tract infection (URTI) symptoms and decreased the number of URTI episodes [362].

When healthy subjects took L. gasseri, B. longum, and B. bifidum in the winter, common cold episodes shortened by almost 2 days and reduced the severity of symptoms [363].

L. acidophilus, B. bifidum and B. animalis plus vitamin C reduced the incidence rate of upper respiratory tract infection, the number of days with symptoms and the absence from preschool in children [364].

According to one study, a synbiotic containing L. acidophilus, B. infantis, and B. bifidum may provide effective control of respiratory infection and wheezing frequency in children under five years old [365].

The intake of yogurt fermented with L. delbrueckii ssp. bulgaricus increased the activity of natural killer cells and reduced the risk of catching a common cold in the elderly [366].

L. acidophilus suppressed all 74 gram-negative and 16 of the gram-positive bacteria commonly found in burn wounds. According to the authors, it may therefore be useful in the prevention of burn wound infections [367].

L. fermentum reduced the duration and severity of respiratory illness in highly trained distance runners [368].

L. fermentum reduced the severity of gastrointestinal and respiratory illness symptoms in male but not female cyclists [369].

L. fermentum reduced gastrointestinal and upper respiratory tract infections in infants [370, 371].

Oral administration of L. fermentum potentiated the immunologic response to the flu vaccine. According to some researchers, this probiotic may enhance systemic protection by increasing the Th1 response and virus-neutralizing antibodies. The incidence of an influenza-like illness in the 5 months after vaccination was decreased in the group that consumed this probiotic [343, 344].

B. longum reduced the incidence of influenza and fever in subjects with influenza vaccination [372].

B. longum fed infants showed a trend toward fewer respiratory tract infections [373].

B. longum ssp. infantis appeared to trigger an anti-poliovirus response in infants [374].

B. breve significantly inhibited rotavirus multiplication and prevented rotavirus infection in infants [375].

B. animalis ssp. lactis reduced days with cold/flu in young healthy adults [376].

Infants and children receiving B. animalis ssp. lactis experienced fewer respiratory tract infections [377, 378].

S. boulardii reduced E. coli numbers in children [379].

In one study, S. boulardii was as effective against B. hominis infection in children as metronidazole [380].

S. boulardii was effective in treating giardiasis when combined with metronidazole therapy in adult patients [381].

The addition of S. boulardii to metronidazole in amebiasis significantly decreased the duration of (bloody) diarrhea and enhanced clearance of cysts in children [382]. It also decreased the duration of symptoms and cyst passage in adults [383].

Prophylactic S. boulardii supplementation appeared to be as effective as nystatin in reducing fungal colonization and invasive fungal infection; it also seemed to be more effective in reducing the incidence of clinical sepsis and the number of sepsis attacks. S. boulardii also had a favorable effect on feeding intolerance in very low birth weight infants [384].

B. subtilis decreased the frequency of respiratory infections in elderly subjects [385].

B. subtilis inhibited disease transmission in patients with acute non-typhoid Salmonella gastroenteritis [386].

Metabolites of B. subtilis decreased the resistance of urogenital pathogenic microflora to antibiotics in patients with urinary tract infections, resulting in accelerated elimination [387].

Probiotics appeared to be effective in the treatment and prevention of urogenital infections in women as alternatives or co-treatments. They also appeared to be effective for the treatment and prevention of bacterial vaginosis, prevention of recurrences of candidiasis and urinary tract infections, and clearing of human papillomavirus lesions. No study reported significant adverse events related to probiotic intervention [388].

Probiotic supplementation with vaginal L. rhamnosus inhibited bacteria growth, especially after antibiotic therapy [389].

According to some researchers, L. rhamnosus vaginal tablets may be a reliable and safe topical treatment to reduce the bacterial vaginosis recurrence rate [390].

Daily ingestion yogurt enriched with L. acidophilus may reduce the episodes of bacterial vaginosis [391]. Treatment of patients with bacterial vaginosis with L. acidophilus contributed to the restoration of a normal vaginal environment [392].

L. fermentum and L. plantarum significantly reduced bacterial vaginosis in women [393].

L. crispatus reduced recurrent urinary tract infections in premenopausal women [394].

L. crispatus inhibited Chlamydia trachomatis, the most common sexually transmitted bacterial pathogen, in human epithelial cells and macrophages [395, 396].

Cervicovaginal mucus with high L. crispatus concentrations may trap the HIV virus and prevent (or delay) systemic infection [397].

B. coagulans reduced vaginosis symptoms in women when co-administered with antibiotics [398].

See individual probiotic posts for more information and animal studies

26) Mucositis

Oral mucositis is one of the most common, debilitating complications of cancer treatments, particularly chemotherapy and radiation. L. brevis reduced the incidence and severity of anticancer therapy-induced oral mucositis and improved the tolerance to chemo-radiotherapy, and anticancer treatment completion [399].

L. acidophilus improved inflammatory and functional aspects of intestinal mucositis caused by chemotherapy in mice [400].

S. boulardii reduced the inflammation and dysfunction of the gastrointestinal tract in mice with intestinal mucositis [401].

In one study, S. thermophilus partially alleviated mucositis induced by administration of the antimetabolite chemotherapy drug methotrexate in rats [402], while in another study no protective effects were observed [403].

S. thermophilus partially prevented the loss of body weight induced by doxorubicin and slightly ameliorated doxorubicin-induced mucositis in rats [404].

S. thermophilus significantly reduced intestinal mucositis severity in rats treated with 5-Fluorouracil [405].

S. cerevisiae reduced oxidative stress, prevented weight loss and intestinal lesions, and maintained the integrity of the mucosal barrier in mice with mucositis [406].

27) Fighting Helicobacter pylori

Frequently used probiotic strains for H. pylori infection are L. johnsonii, S. boulardii, L. acidophilus and B. animalis ssp. lactis [4].

According to some researchers, probiotics may inhibit H. pylori infection by both non-immunological and immunological mechanisms [4].

L. delbrueckii ssp. bulgaricus and S. thermophilus improved H. pylori eradication rates in infected patients [407].

L. acidophilus decreased the viability of H. pylori and increased the eradication rate in infected patients [408].

Multi-strain probiotics, including L. acidophilus/B. animalis, significantly improved H. pylori eradication rates, prevented adverse reactions, and reduced antibiotic-associated diarrhea [409].

L. gasseri suppressed H. pylori and reduced gastric mucosal inflammation in infected patients [410]. A 4-week treatment with L. gasseri-containing yogurt improved the efficacy of triple therapy in patients with H. pylori infection [411]. L. gasseri yogurt also suppressed dyspeptic symptoms in H. pylori-infected patients [412].

Fermented milk containing L. johnsonii co-administered with antibiotics was shown to have a favorable effect on H. pylori gastritis [413].

L. johnsonii inhibited H. pylori colonization in children [414, 415] and in asymptomatic volunteers [416].

A 2-week treatment with L. reuteri significantly reduced H. pylori overgrowth in otherwise healthy adults [417].

B. animalis spp. lactis and inulin significantly reduced treatment side effects and indirectly increased eradication rates by increasing patient compliance in patients with symptomatic H. pylori infection [418].

B. bifidum improved rates of upper gastrointestinal symptomatic subjects and total symptoms in patients with H. pylori infection [419].

The combined use of C. butyricum reduced the changes in the intestinal flora and decreased the incidence of gastrointestinal side effects in patients going through H. pylori eradication therapy [420, 421].

L. brevis treatment decreased H. pylori colonization in dyspeptic H. pylori patients and reduced polyamine biosynthesis [422].

B. subtilis containing probiotics improved H. pylori eradication and decreased diarrhea and total side effects when used in conjunction with triple therapy [277].

S. boulardii reduced the colonization of H. pylori in the human gastrointestinal system, but it does not seem to be able to eradicate infection when used as single therapy [423].

In patients with H. pylori infection, S. boulardii along with standard triple therapy may increase the eradication rates and decrease overall therapy-related side effects, particularly diarrhea [424, 425, 426, 427, 428, 429].

S. boulardii administered in addition to proton pump inhibitor-based triple therapy slightly lowered the incidence of nausea, vomiting, and abdominal pain and significantly lowered the incidence of stomatitis, constipation, and diarrhea in infected children [430].

S. boulardii improved anti-H. pylori therapy-associated diarrhea, epigastric discomfort, and treatment tolerability. In addition, S. boulardii decreased post-treatment dyspepsia symptoms independent of H. pylori status [431].

L. paracasei supplementation prevented bowel symptom onset in patients on long-term proton pump inhibitors [432].

28) Inflammation

Supplementation with a synbiotic, which is a mixture of L. casei, L. rhamnosus, S. thermophilus, B. breve, L. acidophilus, B. longum, L. delbrueckii ssp. bulgaricus, and fructo-oligosaccharides reduced inflammation markers in adults [11].

B. longum ssp. infantis reduced proinflammatory markers in patients with ulcerative colitis, chronic fatigue syndrome, and psoriasis [433].

L. casei improved natural killer (NK) cell activity and produced a more anti-inflammatory cytokine profile in healthy non-immunocompromised elderly subjects [434].

L. paracasei significantly increased the release of pro-inflammatory cytokines and stimulated the innate immune system in human enterocytes and dendritic cells (DCs) [435].

L. delbrueckii ssp. lactis seems to have anti-inflammatory effects [436]. Skimmed milk with L. delbrueckii ssp. bulgaricus inhibits the secretion of proinflammatory cytokines produced by accessory white blood cells [437].

L. acidophilus reduced inflammation in human intestinal epithelial cells [438].

B. animalis ssp. lactis added to yogurt post-fermentation was anti-inflammatory in healthy adults [439].

B. animalis ssp. lactis inhibited inflammation in elderly volunteers [440].

B. longum ssp. infantis suppressed proinflammatory IL-17 cytokine production and may be useful in the treatment of Th17-mediated diseases [441].

In one study, L. reuteri inhibited NF-κB, one of the most important factors in reducing whole-body inflammation [442].

See individual probiotic posts for animal studies and technical information.

29) Autoimmune Disorders

Some researchers believe that probiotics and prebiotics have the potential to curb the autoimmune response. They are being investigated as an alternative to detrimental immunosuppressive drugs [329].

L. johnsonii delayed or inhibited the onset of type 1 diabetes in diabetes-prone rats [443, 444].

Intestinal dysbiosis, characterized by a reduced Firmicutes/Bacteroidetes ratio, has been reported in systemic lupus erythematosus (SLE) patients [445]. B. bifidum supplementation prevented CD4+ lymphocyte over-activation and may help in restoring the Treg/Th17/Th1 imbalance present in patients with SLE [445].

30) Celiac Disease

B. longum ssp. infantis reduced gastrointestinal symptoms in untreated Celiac disease (CD) patients [446].

B. longum improved gut microbiota composition and immune parameters in children with newly diagnosed CD [447].

Oral administration of B. longum ameliorated gliadin (gluten)-mediated perturbations in liver iron deposition and mobilization in rats with CD [448].

B. longum attenuated the production of inflammatory cytokines and the CD4+ T-cell mediated immune response and protected newborn rats against gliadin (gluten)-induced enteropathy [449].

B. breve decreased the production of the pro-inflammatory cytokine TNF in children with Celiac disease on a gluten-free diet [450].

Some researchers think that live B. animalis ssp. lactis bacteria may directly counteract the harmful effects exerted by celiac-toxic gluten (gliadin) to human intestinal cells [451].

L. casei induced complete recovery in mice with enteropathy such as Coeliac disease [452].

31) Liver Disease

Probiotics found in yogurt, L. delbrueckii ssp. bulgaris and S. thermophilus improved liver function [11].

NAFLD

Some probiotics and synbiotics improved liver and metabolic parameters in patients with non-alcoholic fatty liver disease (NAFLD) [11].

In patients with NAFLD, L. acidophilus and B. lactis reduced serum levels of ALT, ASP, TC, and LDL-C [11].

In obese children with NAFLD, L. rhamnosus restored liver function [11].

Bifidobacteria, Lactobacilli, and S. thermophilus treatment for 4 months improved fatty liver severity and decreased BMI of children with NAFLD [11].

L. rhamnosus protected against NAFLD in mice, possibly by increasing beneficial bacteria in the distal small intestine and attenuating liver fat accumulation and portal alanine-aminotransferase concentrations [453].

Treatment with L. plantarum for 5-weeks restored liver function in rats with non-alcoholic fatty liver disease (NAFLD) and decreased the levels of fat accumulation in the liver. In addition, the bacterium significantly reduced proinflammatory cytokines [454].

L. casei protected against the onset of NAFLD in mice [455], and suppressed nonalcoholic steatohepatitis development. According to some researchers, this probiotic may reduce blood lipopolysaccharide concentrations, suppress inflammation and fibrosis in the liver and reduce colon inflammation [456].

A L. paracasei synbiotic (containing arabinogalactan, fructooligosaccharides) lessened NAFLD progression in rats, lowered inflammatory markers and reduced the severity of liver injury and insulin resistance [95].

L. johnsonii protected mice with NAFLD from liver steatosis and liver cell death [112].

C. butyricum increased cholesterol degrading enzymes and improved NAFLD in rats on a high-fat diet [457].

NASH

A synbiotic that contains five probiotics (L. plantarum, L. delbrueckii, L. acidophilus, L. rhamnosus, B. bifidum, and inulin) over 6 months in adults with nonalcoholic steatohepatitis (NASH) produced a significant decrease in intrahepatic triglyceride (IHTG) levels [11].

B. longum and fructo-oligosaccharides (FOS) significantly reduced AST, CRP, HOMA-IR, blood endotoxin and steatosis in patients with NASH [458].

L. paracasei lowered liver fat deposition and serum ALT level in mice with NASH [459].

Alcohol-Induced Liver Injury

L. rhamnosus protected against alcoholic liver injury [460, 461].

L. casei attenuated alcohol-induced liver cell damage [462].

In chronic alcohol-induced mice, whey fermented with L. casei significantly attenuated the increased levels of ALT, AST and triglyceride levels, increased antioxidant activity, and improved liver parameters [463].

L. paracasei reduced total blood and liver cholesterol in rats and decreased liver damage due to alcohol intake [464].

L. fermentum significantly alleviated liver damage in mice with alcoholic liver disease [465, 466].

Oral administration of L. brevis ameliorated alcohol-induced liver injury and the fatty liver in mice. It significantly inhibited ALT and AST increase and decreased TG and total cholesterol in the liver [467].

Jaundice

Treatment of obstructive jaundice in rats with L. plantarum returned active liver barrier functions [468].

Liver Injury

L. plantarum protects against oxidative stress and liver inflammatory injury in mice [469].

L. casei significantly improved the survival of rats with liver injury, via its anti-oxidative and anti-inflammatory capacities [470].

Pretreatment with L. salivarius improved acute liver injury in rats [471].

L. salivarius is believed to promote health in acute liver failure [472].

L. paracasei restored gut microbiota and attenuated ischemia/reperfusion-related liver injury in rats [473].

S. boulardii effectively prevented liver injury induced by Salmonella Enteritidis infection in mice [474].

Cirrhosis

B. faecium and B. subtilis shifted the intestinal microbiota of patients with liver cirrhosis back towards levels observed in healthy subjects. These probiotics also reduced circulating endotoxin levels in cirrhotic patients with endotoxemia [277].

B. longum and FOS improved biochemical parameters and neuropsychological tests in cirrhotic patients with minimal hepatic encephalopathy (MHE) [475].

S. boulardii promoted liver function and slowed down the progress of liver fibrosis in rats [476].

32) Allergies

Probiotics harmonized Th1/Th2 imbalance in allergic conditions in adults [477].

Systemic Allergies

L. brevis suppressed systemic anaphylaxis [478] and inhibited IgE production and histamine secretion in allergic mice [479].

L. casei protected mice from acute allergic inflammation (anaphylaxis) [480].

Allergies in Newborns

Consumption of L. rhamnosus-fermented milk by mothers and offspring was associated with a reduction in physical allergic symptoms in newborn mice [477].

Neonatal mother-to-offspring colonization with B. longum reduced allergic responses in mice [481].

Asthma

Human Studies:

L. salivarius decreased the secretion of proinflammatory cytokines and showed beneficial immunomodulatory activity in asthmatic subjects [482].

B. breve showed promising probiotic properties and beneficial immunomodulatory activity in allergic asthma [483].

C. butyricum improved asthma and serum specific IgE in the patients treated with specific immunotherapy (SIT), increased IL-10, and converted antigen-specific B cells to regulatory B cells [484].

Animal Studies:

Oral administration of L. rhamnosus attenuated the features of allergic asthma in mice [485, 486].

L. salivarius decreased allergen-induced airway response in mice [487]. It also alleviated asthma symptoms like airway hyperreactivity and airway inflammation in mice [488].

L. gasseri attenuated allergen-induced airway inflammation and IL-17 pro-inflammatory immune response in mice with allergic asthma [489].

L. lactis significantly attenuated atopic esophageal and bronchoalveolar eosinophilic inflammation in mice [490].

B. breve had strong anti-inflammatory properties in asthmatic mice [491, 492, 493].

L. paracasei administration to mothers during gestation/lactation protected against airway inflammation in mice offspring [494].

B. longum attenuated allergic airway inflammation in mice [495].

B. bifidum significantly decreased airway hyperresponsiveness, decreased lung inflammation and lowered the Th2 response in allergic mice [496, 497].

Allergic Rhinitis

17 out of 22 trials in a review showed a significant benefit of probiotics clinically, whereas eight trials showed significant improvement in immunologic parameters in allergic rhinitis [498].

Citrus juice fermented by L. plantarum improved the symptoms of Japanese cedar pollinosis [499].

C. butyricum markedly enhanced the efficacy of SIT on allergic rhinitis in patients with allergies [500].

Co-administration of C. butyricum markedly enhanced the treatment of allergic rhinitis [500].

L. rhamnosus supplementation showed good clinical and immunologic response in children with allergic rhinitis [501].

Volunteers with seasonal allergic rhinitis treated with L. casei showed a significant reduction in levels of antigen-induced cytokines [502].

A significant reduction of nasal symptoms and improved quality of life were achieved in patients with Japanese cedar pollinosis, who received L. paracasei when pollen scattering was low. However, the effects were limited during the peak period [503].

At least five clinical studies with L. paracasei demonstrated clinically significant improvements in allergic rhinitis [498], while one did not [504].

Subjects with a medical history of allergic rhinitis to grass pollen that received L. paracasei-fermented milk had lower nasal congestion and less nasal itching [505].

In children with perennial allergic rhinitis, L. paracasei improved symptoms of sneezing, itchy nose, and swollen eyes [506].

L. paracasei improved the quality of life of subjects with persistent allergic rhinitis who were being treated with an oral H1-antihistamine. In this study, nasal symptoms did not change, but ocular symptoms consistently improved [507].

Heat-killed L. paracasei effectively improved the overall quality of life in patients with allergic rhinitis induced by house dust mite [508].

L. acidophilus alleviated allergic symptoms in patients with Japanese cedar pollinosis [509, 510].

L. acidophilus alleviated the symptoms in patients with perennial allergic rhinitis [511].

Heat-killed L. gasseri improved nasal symptoms and pollen-specific IgE levels in subjects with Japanese cedar pollinosis [512].

The addition of L. johnsonii to levocetirizine improved perennial allergic rhinitis in children [513].

Intake of yogurt or powder supplemented with B. longum alleviated subjective symptoms and affected blood markers of allergy in individuals with Japanese cedar pollinosis [514, 515, 516]. Nasal symptoms such as itching, rhinorrhea, and blockage, as well as throat symptoms, tended to be relieved with this probiotic [517].

B. animalis ssp. lactis improved nasal symptoms in subjects suffering from seasonal allergic rhinitis [518].

Check individual posts for more information and animal studies.

Food Allergies

L. rhamnosus accelerated oral tolerance acquisition in cow’s milk allergic infants [519, 250].

L. rhamnosus decreased the allergic response to peanuts in children [520].

In one study of milk-hypersensitive adults, L. rhamnosus reduced the immunoinflammatory response [250].

L. plantarum reduced the allergenicity of soy flour [521].

L. salivarius, L. paracasei, B. animalis and B. bifidum prevented atopic sensitization to common food allergens. The authors of this study believe that this probiotic blend could thereby reduce the incidence of atopic eczema in early childhood [522].

L. delbrueckii ssp. bulgaricus degraded the allergenic whey protein β-lactoglobulin and inhibited IgE binding in allergic patients [523].

L. helveticus alone or in combination with S. thermophiles effectively reduced the antigenicity of α-lactalbumin and β-lactoglobulin, the major allergens in cow’s milk [524].

L. helveticus can significantly degrade the major allergens in propolis, including esters of caffeic acid [525].

L. fermentum degraded αS1-casein and lowered the recognition and the binding of this casein to IgE from the blood of patients with cow’s milk allergy [526].

B. breve improved symptoms of allergic hypersensitivity to cow’s milk in infants [527].

Eczema

The combination of prenatal maternal (2 – 4 weeks) and postnatal pediatric (6 months) L. rhamnosus treatment in families with a history of atopic disease, significantly lowered the risk of eczema at the age of 2, 4 and 7 [250].

In infants receiving either L. rhamnosus or B. lactis after 2 months, eczema symptoms were significantly improved [187].

L. rhamnosus efficiently prevented the development of eczema and possibly also atopic sensitization in high-risk infants up to 6 years old [528].

Cumulative prevalence of eczema and the prevalence of rhinoconjunctivitis were significantly reduced in the children taking L. rhamnosus [529].

B. animalis ssp. lactis significantly improved eczema symptoms in infants [530].

When administered to pregnant women with a family history of allergic diseases, a mixture of B. bifidum, B. lactis, and L. acidophilus significantly lowered the prevalence and incidence of eczema in infants at high risk of allergy [531].

B. breve reduced the risk of developing eczema and atopic sensitization in infants at high risk of allergic disease [532].

B. bifidum had a positive effect on the prevention and treatment of eczema in infants [533].

The use of multi-strain probiotics appeared to be most effective for eczema prevention [534].

Atopic Dermatitis

The use of L. rhamnosus by mothers lowered the risk of developing atopic dermatitis during the first 2 years of life [187].

L. rhamnosus decreased symptoms of atopic dermatitis after an 8-week treatment in children aged 4 – 48 months [535].

Daily intake of citrus juice containing heat-killed L. plantarum alleviated symptoms of atopic dermatitis in humans [536].

L. salivarius improved symptoms in children [537, 538] and adults with atopic dermatitis [539].

Heat-killed L. paracasei improved atopic dermatitis (AD) in adult patients [540].

Long-term oral administration of L. acidophilus restored Th1/Th2 balance and ameliorated the symptoms of atopic dermatitis in children [541].

Prolonged ingestion of L. acidophilus significantly decreased the eczema area and severity index in patients with adult atopic dermatitis [542, 543]. The probiotic also suppressed scratching behavior [542].

B. breve improved symptoms of atopic dermatitis in infants [527, 544].

Topical administration of an S. thermophilus-containing cream to patients with atopic dermatitis increased ceramide levels and improved the signs and symptoms of atopic dermatitis (i.e. erythema, scaling, pruritus) [545].

See individual probiotic posts for more information and animal studies.

33) Lactose Intolerance

L. delbrueckii ssp. bulgaricus and S. thermophilus improved lactose digestion in the gastrointestinal tract and reduced symptoms of lactose intolerance [546].

L. acidophilus may improve lactose digestion and tolerance [547, 548].

34) Histamine Intolerance

L. plantarum is able to degrade biogenic amines ®; thus, some researchers believe it could help with histamine intolerance.

L. casei degrades biogenic amines (BAs) and reduces histamine and tyramine accumulation in cheese [549].

Note that some probiotics may produce or increase biogenic amines (see Safety section).

35) Oxalate

L. gasseri degraded oxalate in laboratory experiments; according to some researchers, it may therefore be beneficial in managing oxalate kidney stone disease [550].

A mixture of L. casei and B. breve lowered urinary oxalate excretion through a mechanism that may be dependent on dietary oxalate intake [551].

B. animalis ssp. lactis possesses the oxc gene, encoding oxalyl-coenzyme A (CoA) decarboxylase, a key enzyme in oxalate degradation [552]. B. animalis ssp. lactis significantly decreased urinary oxalate excretion in mice with hyperoxaluria, possibly by degrading dietary oxalate and thus limiting its absorption across the intestine [553].

36) Skin Health

According to one study, probiotics may be able to restore acidic skin pH, alleviate oxidative stress, attenuate photoaging, improve skin barrier function, and enhance hair quality [554].

Some researchers believe that the topical application of probiotic bacteria may enhance the skin’s natural defense barriers. Additionally, probiotics, as well as resident bacteria, can produce antimicrobial peptides that benefit skin immune responses and eliminate pathogens [555].

Human Studies:

L. plantarum improved skin hydration prevented the photoaging of human skin [556, 557]. L. plantarum further increases hydration and may help to improve skin barrier function [557].

L. plantarum inhibited the degradation of collagen, promoted collagen synthesis, and decreased reactive oxygen species (ROS) production [558].

In clinical trials, L. plantarum significantly increased the skin water content in the face and hands. Volunteers in the probiotic group had a significant reduction in wrinkle depth at week 12, and skin gloss was also significantly improved by week 12. Skin elasticity in the probiotic group improved by 13.17% after 4 weeks and by 21.73% after 12 weeks [559].

L. paracasei may contribute to the reinforcement of skin barrier function, inhibit water loss, decrease skin sensitivity, and modulate the skin immune system, leading to the preservation of skin homeostasis [560].

L. paracasei decreased skin sensitivity and increased barrier function recovery (water retention) in women [561].

L. johnsonii significantly inhibited the development of UVA-induced skin lesions in clinical studies [562].

Supplementation with L. rhamnosus normalized skin expression of genes involved in insulin signaling and improved the appearance of adult acne [563].

B. longum extract, when applied to the skin, appeared to improve inflammation parameters, decrease skin sensitivity, increase skin resistance against physical and chemical aggression, and decrease skin dryness in volunteers with sensitive skin [564].

B. breve and galactooligosaccharides (GOS) increased skin hydration and clearness in healthy young and adult women [565, 566].

L. lactis increased sebum content, thereby potentially reinforcing the skin barrier in healthy young women [567]. L. lactis maintained skin hydration and improved subjective skin elasticity in middle-aged Japanese women [568].

Ceramides play an essential role in the barrier and water-holding functions of healthy skin. A significant increase in skin ceramide levels was observed in healthy subjects after treatment with a cream containing a preparation of S. thermophilus [569].

Topical treatment with an S. thermophilus-containing cream increased ceramide levels and increased hydration in the skin of healthy elderly women [570].

S. cerevisiae extract (SCE) is used in cosmetics to reduce oxidative stress and improve skin conditions. It enhanced skin moisture and skin microrelief in volunteers [571].

Animal Studies:

In hairless mice, L. plantarum decreased UVB-induced epidermal thickness, suppressed water loss and increased the ceramide level [572, 573].

B. longum exerted photoprotective effects on the skin in mice [574].

B. bifidum decreased the amount of intracellular melanin and exhibited antioxidant properties in mice [575].

B. breve prevented water loss, improved skin elasticity and hydration, and attenuated the damage induced by chronic UV irradiation (photoaging) in mice [576, 577, 578].

L. brevis increased blood flow and decreased transepidermal water loss in rats. Some researchers believe that it could be a useful substance in the treatment and prevention of skin problems, specifically chapped or dry skin [579].

Animal research on L. reuteri has shown potential for improving skin quality (thickness and “glow”) and promoting thick, lustrous hair [580].

37) Hemodialysis

Oral administration of B. longum decreased serum phosphate levels in patients receiving hemodialysis (HD) [581].

The administration of B. longum also decreased the concentrations of indoxyl sulfate and P-cresol in HD patients [582, 583].

In addition, Bifidobacteria produce vitamin B12 and folate, which may normalize serum homocysteine levels in HD patients [581].

38) Wound Healing

L. plantarum reduced the bacterial load of infected chronic venous ulcer wound, reduces neutrophils, apoptotic and necrotic cells, and induced wound healing in both diabetics and non-diabetics [584].

Topical treatment with a water-insoluble glucan from S. cerevisiae may enhance venous ulcer healing in humans. In a patient who had an ulcer that would not heal for over 15 years, this treatment caused a 67.8% decrease in the area of the ulcer [585].

Supplementing the rat microbiome with L. reuteri in drinking water cut wound-healing time in half compared to control animals [586].

39) Toxins and Pollutants

Dietary exposure to heavy metals has detrimental effects on human and animal health, even at low concentrations. L. rhamnosus and P. freudenreichii, alone or in combination, were found to bind cadmium and lead efficiently at the low concentration ranges commonly observed in foods [587].

Furthermore, dietary supplementation with L. rhamnosus reduced the absorption and toxicity of consumed organophosphate pesticides in Drosophila [588].

L. plantarum alleviated cadmium-induced cytotoxicity in human intestinal cells and mice in the laboratory [589, 590].

L. plantarum protected against aluminum toxicity in mice, possibly by reducing intestinal aluminum absorption and tissue accumulation and ameliorating liver damage, kidney, and brain oxidative stress [591].

Treatment with L. plantarum alleviated copper toxicity, possibly by increasing copper excretion and reducing the accumulation of copper in tissues. L. plantarum also reversed oxidative stress induced by copper exposure, recovered the ALT and AST blood levels and improved the spatial memory of mice [592].

L. casei and L. helveticus may bind to and inactivate heterocyclic aromatic amines (HACs), the most abundant mutagens in fried red meat, decreasing their concentration and their toxicity [593, 155].

L. casei decreased the cytotoxic effects of pesticides on human cells [593].

L. casei supplementation reduced the level of aflatoxin in blood and improved the adverse effects of aflatoxin on body weight and blood parameters in rats [594, 595]. According to one study, a fermented milk drink containing L. casei may reduce aflatoxin toxicity in humans [596].

L. paracasei reduced the adverse effects of Zearalenone (ZEN), an estrogenic toxin produced by Fusarium fungi species in pre- or post-harvest cereals in mice [597].

Organophosphorus hydrolase (OpdB) from L. brevis is able to degrade organophosphorus pesticides [598].

S. cerevisiae possesses the ability to bind and degrade mycotoxins [17]. S. cerevisiae improved weight gain and reduced genotoxicity of aflatoxin in mice fed with contaminated corn [599].

40) MSG

Capsules containing L. brevis reduced monosodium glutamate (MSG) levels and MSG symptom complex in humans [600].

L. brevis inhibited the absorption of MSG from the intestine into the blood in mice [601].

41) Testosterone Levels

L. reuteri sustained youthful serum testosterone levels and testicular size in aging mice [602, 580].

A probiotic containing L. acidophilus, B. bifidum, and L. helveticus elevated testosterone levels in rabbits [603].

42) Oxytocin

L. reuteri increased the levels of the “feel-good” hormone oxytocin [580].

43) Fatigue

L. acidophilus reversed immune dysfunction in fatigued athletes [604].

L. acidophilus decreased chronic fatigue following exercise and attenuated stress in rats [605].

L. gasseri prevented the reduction in natural killer (NK) cell activity due to strenuous exercise and elevated mood from a depressed state in university-student athletes [606].

L. gasseri and αLA alleviated minor resting fatigue in university-student athletes after strenuous exercise [606].

44) Muscle Recovery and Athletic Performance

B. coagulans enhanced protein absorption in fit men. The authors concluded that it may thereby indirectly improve recovery and training adaptations [607].

B. coagulans in combination with protein reduced muscle damage and soreness, improved recovery, and maintained physical performance in athletes after strenuous exercise [607].

An increase in vertical jump power was noted following 8 weeks of full-body workouts 4-times per week daily while ingesting B. coagulans, compared with the group that trained without taking probiotics [607].

Four weeks of supplementation with a multi-strain probiotic increased running time to fatigue in the heat in male runners [608].

L. plantarum significantly decreased body weight and increased relative muscle weight, grip strength and endurance swimming time in mice [609].

45) Arthritis

Human Studies:

L. casei supplementation helped alleviate symptoms and improve inflammatory cytokines in women with rheumatoid arthritis [610].

A mix of L. acidophilus, L. casei and B. bifidum improved rheumatoid arthritis, decreased insulin levels, and improved total- and low-density lipoprotein cholesterol levels [611].

Adjunctive treatment with B. coagulans was safe and effective for patients suffering from rheumatoid arthritis. B. coagulans improved pain, improved self-assessed disability, and reduced CRP levels. It also was associated with improved ability to walk 2 miles, reach for objects, and participate in daily activities [612].

Animal Studies:

L. casei protected mice from autoimmune arthritis [480]. Consumption of L. casei prior to infection prevented the intestinal and joint inflammation triggered by Salmonella in mice [189].

L. casei reduced pain, inflammatory responses, and articular cartilage degradation in arthritic mice. L. casei together with glucosamine decreased expression of various pro-inflammatory cytokines and matrix metalloproteinases, while up-regulating anti-inflammatory cytokines [613].

Similarly, L. casei effectively suppressed symptoms of rheumatoid arthritis in rats: the symptoms that saw improvement included paw swelling, lymphocyte infiltration, and destruction of cartilage tissues. Anti-inflammatory cytokines were increased, while pro-inflammatory cytokines were decreased [614, 615, 616].

Oral intake of skimmed milk fermented with L. delbrueckii ssp. bulgaricus markedly inhibited the development of arthritis in mice [617].

L. acidophilus decreased arthritis symptoms and maintained normal histology of reproductive organs in rats [618].

L. acidophilus showed effects comparable to the drug indomethacin in decreasing organ damage associated with arthritis in rats. This probiotic down-regulated pro-inflammatory and up-regulated anti-inflammatory cytokines [619].

L. helveticus strongly alleviated symptoms of arthritis in mice [286].

B. coagulans significantly inhibited fibrinogen (Fn), blood amyloid A, and pro-inflammatory cytokine production in arthritic rats [620].

46) Dental Health

Some researchers believe that probiotics may be beneficial for managing gingivitis or periodontitis [621].

L. rhamnosus reduced oral counts of Streptococcus mutans, a bacterium correlated with caries formation [250].

L. casei had bactericidal effects on all analyzed species isolated from dental plaque, while the mixed culture of L. acidophilus and B. animalis had only a bacteriostatic effect [622].

S. thermophilus inhibited the growth of P. gingivalis and reduced the emission of volatile sulfur compounds that can cause oral malodor [623].

A bacteriocin produced by L. paracasei inhibited P. gingivalis, a species strongly associated with periodontal disease [624].

Human Studies:

Long-term consumption of L. rhamnosus containing milk reduced caries development in children [250].

Heat-killed L. plantarum decreased the depth of periodontal pockets in patients undergoing supportive periodontal therapy [330].

Oral administration of L. casei reduced the number of pathogenic (periodontopathic) bacteria in healthy volunteers with mild to moderate gum inflammation (periodontitis) [625].

L. salivarius beneficially changed the bacterial population of gum plaque in volunteers [626].

L. salivarius increased resistance to caries risk factors in volunteers [627].

Oral administration of L. salivarius improved bad breath, showed beneficial effects on bleeding on probing from the periodontal pocket, and inhibited the reproduction of “bad” bacteria [628, 629, 630, 631].

Oral L. paracasei significantly reduced salivary S. mutans [632, 633, 634], and increased Lactobacilli in adults [634].

L. brevis improves pH, significantly reduced salivary mutans streptococci and bleeding on probing in high caries risk schoolchildren [635].

L. brevis had anti-inflammatory effects and brought about the total disappearance or amelioration of clinical symptoms in patients with periodontitis [636].

L. brevis exerted anti-inflammatory properties. possibly by preventing nitric oxide synthesis, and may delay gingivitis development in humans [637].

B. subtilis reduced periodontal pathogens in humans [638].

Oral L. reuteri containing tablets significantly reduced inflammation in patients with chronic periodontitis [639].

Animal Studies:

L. brevis inhibited periodontal inflammation, significantly decreased bone loss and lowered the count of anaerobic bacteria in mice with periodontitis [640].

B. subtilis and Bacillus licheniformis supplementation provided a protective effect against bone loss in rats with periodontitis [641].

S. cerevisiae, as monotherapy or as an adjuvant, accelerated the tissue-repair process and ameliorated periodontitis in rats [642].

47) Lung Injury and Inflammation

B. longum treatment significantly improved lung injury following infection and sepsis in mice. This probiotic also decreased lung inflammatory responses [643].

48) For Smokers

Cigarette smoking reduces natural killer cell (NK cell) activity. L. casei intake prevented the smoke-dependent NK activity reduction in Italian male smokers [644].

In healthy shift workers, L. casei reduced the total number of clinical infectious diseases (CIDs) in the subgroup of smokers [359].

B. breve suppressed inflammatory agents in macrophages; some researchers believe it may be useful in cigarette smoke-associated diseases such as Chronic obstructive pulmonary disease (COPD) [645].

L. salivarius improved periodontal clinical parameters in smokers [646].

49) Bone Health

The gut helps regulate bone health through the absorption of calcium, the key bone mineral [647].

Administration of probiotics led to higher bone mineralization and greater bone strength in animals. The preferential bacterial genus that has shown these beneficial effects in bone is Lactobacillus [648].

L. helveticus increased serum calcium levels in geriatric volunteers [24].

L. helveticus fermented milk whey contains bioactive components that may increase bone formation [649].

L. helveticus-fermented milk prevented bone loss, possibly by decreasing bone turnover and increasing bone mineral density in rats [650, 651].

B. longum supplementation alleviated bone loss and increased bone formation parameters and bone mass density in ovariectomized rats [652].

50) Female Fertility

L. plantarum ameliorated inflammation-induced infertility in mice [653].

L. plantarum reinforced natural microflora and lead to a resurge of fertility in mice infected with E. coli [654].

51) Endometriosis

L. gasseri improved menstrual pain and dysmenorrhea in patients with endometriosis [655].

L. gasseri also inhibited the growth of endometrial tissue in the abdominal cavity in mice and rats [656].

52) Pregnancy

The use of a specific set of probiotics during the first 1,500 days of life may lower the risk of infections and inflammatory events in infants [657].

L. rhamnosus affected the immune regulation and immune responses favorably in mothers and offspring. In addition, some of the beneficial effects of prenatal L. rhamnosus supplementation extended into postnatal life of the offspring, suggesting a possible immune programming effect of L. rhamnosus [658].

Prenatal supplementation with L. rhamnosus has been reported to change the composition of the newborn microbiota, promoting a beneficial profile dominated by Bifidobacteria [250].

The intake of milk fermented with L. casei during the lactation period modestly contributed to the modulation of the mother’s immunological response after delivery and decreased the incidence of gastrointestinal episodes in the breastfed child [659].

B. animalis spp. lactis supplementation in pregnancy has the potential to influence fetal immune parameters as well as immunomodulatory factors in breast milk [660].

B. animalis ssp. lactis mitigated the negative immune-related effects of not breastfeeding and cesarean delivery by augmenting the immune response, evidenced by increased anti-rotavirus- and anti-poliovirus-specific IgA [661].

Oral administration of L. salivarius during late pregnancy appeared to prevent breast infection in pregnant women [662].

L. acidophilus, L. casei and B. bifidum significantly decreased fasting plasma glucose, insulin levels, and insulin resistance and increased insulin sensitivity in pregnant women with gestational diabetes mellitus. In addition, significant decreases in serum triglycerides and VLDL cholesterol concentrations were recorded [663].

B. coagulans containing symbiotic decreased blood insulin levels, HOMA-IR, and HOMA-B in pregnant women [664].

Preeclampsia is associated with an impaired antioxidant defense that results in maternofetal complications. S. cerevisiae scavenged nitric oxide radicals and decreased oxidative stress in red blood cells and alleviated stress status in the preeclamptic fetus [665].

Continuous consumption of fermented milk containing L. casei alleviated constipation-related symptoms, provided satisfactory bowel habit, and resulted in earlier recovery from hemorrhoids in women after childbirth [666].

L. fermentum alleviated pain and reduced the load of Staphylococcus in the breastmilk of women suffering from painful breastfeeding [667].

53) Infant Growth

B. animalis spp. lactis supplementation had a positive effect on growth in vulnerable infants, such as infants born to mothers with HIV [668], and preterm infants [669].

B. breve significantly decreased aspirated air volume and improved weight gain in very low birth weight infants [670].

L. plantarum strain maintained the growth of infant mice during chronic undernutrition [671].

54) Feeding Tolerance in Infants

Preterm infants supplemented with B. coagulans had improved feeding tolerance [672].

Prophylactic supplementation of S. boulardii improved weight gain and feeding tolerance and had no adverse effects in preterm infants >30 weeks old [673].

Orally administered S. boulardii reduced feeding intolerance and clinical sepsis in very-low-birth-weight (VLBW) infants [674].

55) Healthy Aging

Human Studies:

Levels of Bifidobacteria decrease as we age [675].

B. animalis spp. lactis beneficially modified gut microbiota in the elderly, increasing Bifidobacteria, Lactobacilli, and Enterococci and reducing Enterobacteria [676].

B. animalis spp. lactis enhanced natural immunity in healthy elderly subjects [677]. B. animalis spp. lactis increased leukocyte phagocytic and NK cell tumor-cell-killing activity in the elderly and increases the proportions of total, helper (CD4(+)), and activated (CD25(+)) T lymphocytes and natural killer cells [678, 679, 680].

B. longum stimulated the immune functions in the elderly [681].

B. bifidum and L. acidophilus positively modulated the immunological and inflammatory responses in elderly subjects [682].

Some researchers believe that L. delbrueckii ssp. bulgaricus may favor the maintenance of an adequate immune response in the elderly, possibly by slowing the aging of the T-cell subpopulations and increasing the number of immature T cells which are potential responders to new antigens [683].

L. acidophilus increased Bifidobacteria levels and beneficially changed microbiota in elderly subjects [684].

Heat-killed L. gasseri enhanced immunity in the elderly. This probiotic increased the number of CD8(+) T cells and reduced CD28 expression loss in CD8(+) T cells [685].

Animal Studies:

Feeding of probiotic bacteria (L. reuteri) to aged mice induced integumentary changes mimicking peak health and reproductive fitness characteristic of much younger animals [686].

Probiotic Dahi with L. lactis, L. acidophilus and B. bifidum reversed age-related decline in expression of biomarkers of aging, PPAR-α, SMP-30, and Klotho in hepatic and kidney tissues in mice [687].

L. lactis along with L. acidophilus or combined with L. acidophilus and B. bifidum reversed age-related decline in immune functions and improve lymphocyte functions in aging mice [688].

Heat-killed L. gasseri increased natural killer cell (NK cell) activities and enhanced cell-mediated immunity in aged host animals, thereby altering age-related immunosenescence [689].

Dahi containing L. acidophilus was effective in reversing age-related immune function decline in mice [690], where this probiotic also combated oxidative stress and molecular alterations associated with aging [691].

L. fermentum alleviated immunosenescence, possibly by enhancing antioxidant enzyme activities and was shown to reduce E. coli infection in aging mice [692].

L. johnsonii helped recover nutritional status and systemic immune responses in aged mice [693].

Long-term oral intake of L. lactis suppressed the reduction of bone density and body weight in senescence-accelerated mice [694].

B. bifidum delayed immunosenescence in mice by enhancing the anti-oxidation activity in thymus and spleen and by improving immune function [695].

Intake of heat-killed L. lactis altered the intestinal flora, affected plasma metabolite levels, including fatty acid levels, and slowed down age-related hearing loss in mice. Researchers have suggested that this probiotic may have inhibited the loss of neurons and hair cells in mouse inner ear [696].

In mice, L. reuteri increased thyroid size and activity (increasing T4 levels), lessening fatigue and weight gain associated with aging and resulting in a more youthful physical appearance [697].

56) Pain

Oral administration of L. acidophilus induced the expression of mu-opioid and cannabinoid receptors in intestinal epithelial cells and mediated analgesic functions in the gut similar to the effects of morphine [698].

B. coagulans + fructooligosaccharide (FOS) decreased abdominal pain duration and frequency in children with GI disorders [699].

A B. coagulans synbiotic improved childhood functional abdominal pain [700].

B. coagulans significantly improved abdominal pain and the quality of life in adults with postprandial intestinal gas-related symptoms and no GI diagnoses [701].

In animal models of gut pain, L. reuteri has been associated with decreased activation of the nervous system and reduced pain [702, 703].

L. reuteri ingestion impacted the nerves in such a way that it may slow gut motility (improving cases of diarrhea) and decrease pain perception [704].

L. rhamnosus may attenuate neonatally induced chronic visceral pain; it significantly altered levels of serotonin, noradrenaline, and dopamine in rats [705].

57) After Surgery

A symbiotic containing L. acidophilus, L. rhamnosus, L. casei, B. bifidum, and fructooligosaccharides reduced postoperative mortality, lowered the incidence of postoperative infections, shortened the duration of antibiotic therapy, and decreased noninfectious complications. These developments resulted in shorter overall hospital stays in patients undergoing surgery for periampullary neoplasms [706].

Orally administered B. breve improved the intestinal environment and suppressed bacterial translocation in pediatric surgical cases [707, 708].

58) Against Candida

Clinical trials have suggested that probiotics may reduce oral, vaginal, and enteric colonization by Candida. Probiotics alleviated clinical signs and symptoms, and, in some cases, reduced the incidence of invasive fungal infection in critically ill patients [709].

In patients with vulvovaginal candidiasis, L. plantarum reduced vaginal discomfort after conventional treatment, improved vaginal bacteria content, and restored vaginal pH [710].

In a clinical trial, L. plantarum use was associated with a three-fold reduced risk of recurrence of vulvovaginal candidiasis [711].

L. fermentum and L. acidophilus maintained the vaginal biofilm and hindered persistent vulvovaginal infection caused by Candida in women [712].

L. reuteri alone or with L. rhamnosus inhibited the growth of Candida in the vagina [713, 714].

L. rhamnosus may prevent enteric colonization by Candida species in preterm neonates [250].

Oral L. reuteri supplementation suppressed candidiasis as effectively as nystatin in preterm infants. It was also more effective at reducing the incidence of sepsis [715, 716].

L. reuteri lozenges were shown to fight oral candida in a study of older patients [717].

S. cerevisiae, when administered orally, colonized the bowel of healthy volunteers; some researchers believe it could compete with and potentially replace resident Candida species [718].

Vaginal administration of S. cerevisiae positively influenced the course of vaginal candidiasis by accelerating the clearance of Candida [719].

See individual probiotic posts for more information and animal studies.

59) Heat Stress

Exposure to extreme heat can cause illnesses and injuries. B. subtilis was effective in the prevention of complications related to heat stress in rats. When rats were subjected to heat stress (45°C), adverse effects such as morphological changes in the intestine, bacterial translocation, elevated levels of LPS and IL-10, and increased vesiculation of erythrocytes were observed only in animals not protected with B. subtilis [720].

60) HIV-Positive Patients

Treatment with S. boulardii decreased microbial translocation (LBP) and inflammation parameters in HIV-1-infected patients with long-term virologic suppression [721].

61) Cancer

Probiotic bacteria have shown antitumor activities, and some studies suggest they could potentially reduce the incidence of cancer. They may delay cancer onset and progression as well as regulate cell growth mechanisms [722].

Studies in Humans:

Consumption of soy isoflavones in combination with L. casei decreased the risk of breast cancer among Japanese women [723].

L. casei administration significantly reduced the recurrence rate of bladder cancer and colorectal cancer in cancer patients [724].

Animal Studies:

L. rhamnosus decreased the incidence of colon tumors and precancerous lesions in experimental animals as well as in human cells [722]. This species also demonstrated antitumor effects in animal models of bladder cancer [725].

L. plantarum enhanced the anti-tumor immune response and delayed tumor formation in mice with intestinal adenocarcinoma [726] and exhibited anti-colorectal cancer activities [727].

Long-term administration of L. plantarum suppressed breast cancer in rats [728, 729] and inhibited the development of rat colon carcinogenesis [730].

L. casei decreased cell migration and invasion of colorectal cancer cells [731, 732], inhibited human and mouse colon cancer cell growth, and resulted in an 80% reduction in tumor volume of treated mice [733].

L. casei delayed and suppressed tumor growth in mice with breast cancer, both when it was administered preventively and as a treatment. L. casei further reduced tumor vascularity and lung metastasis and prolonged survival [734, 735, 736].

Similarly, L. casei decreased breast tumor volume and tumor vascularity in rats [723].

L. salivarius suppressed colon carcinogenesis [737] and inhibited oral cancer growth in rats [738].

L. delbrueckii ssp. bulgaricus inhibited intestinal carcinogenesis in rats, ear-duct tumors in rats, and tracheal carcinogenesis in hamsters [739]. This probiotic was also reported to inhibit the growth of sarcoma [740], leukemia, plasmacytoma, adenocarcinoma, melanosarcoma, and spontaneous tumors in mice [741].

L. acidophilus altered the cytokine production in tumor-bearing mice into a Th1 protective pattern, favorable to anti-tumor immunity [742].

L. acidophilus suppressed colon tumor incidence, tumor multiplicity, and reduced tumor size in mice [743].

Oral administration of L. acidophilus increased mouse survival [744], decreased tumor growth and increased lymphocyte proliferation in mice with breast tumors [742].

L. acidophilus reduced tumor volume growth by 50.3 %, reduced the severity of colonic carcinogenesis, and enhanced cancer cell death in mice [745].

L. helveticus inhibited the development of fibrosarcoma [746] and delayed the development of breast tumors in mice [746].

Dietary B. longum significantly inhibited colon and liver and small intestinal tumors in male rats. In female rats, dietary supplementation also suppressed mammary carcinogenesis [747].

L. longum inhibited colorectal tumors in mice [748] and rats [749, 750].

B. animalis ssp. lactis decreased the mean number and size of tumors in mice with colitis-associated cancer [290].

The synbiotic combination of carbohydrate ‘resistant starch‘ and B. animalis ssp. lactis protected against the development of colorectal cancer (CRC) in rats [751, 752].

Heat-inactivated C. butyricum displayed antitumor activity against sarcoma in mice [753] and inhibited the metastasis of melanoma, possibly by stimulating natural killer (NK) cell cytotoxic activity [754].

Furthermore, in mice, co-treatment with C. butyricum and B. subtilis inhibited the development of colorectal cancer [4].

An antitumor molecule derived from L. brevis inhibited colon adenocarcinoma cell viability and the growth of these cells in mice [755].

Mice with fibrosarcoma that were treated by S. thermophilus were protected against this tumor when re-challenged. Additionally, spleen T-lymphocytes from cured animals could effectively transfer the antitumor activity to recipients transplanted with the tumor [756].

P. freudenreichii killed colon cancer cells in rats [757].

62) Toxins and Carcinogens in the Gut

In a cell-based study, Lactobacillus rhamnosus GG bound to mold toxins purported to cause “leaky gut” and inflammation. Some researchers therefore believe that L. rhamnosus could potentially prevent the negative effects of mold toxins in the gut [758, 759].

In rats, Lactobacillus and other lactic acid bacteria protected the gut and liver cells from cancer-causing chemicals found in foods, such as heterocyclic amines [760, 761].

Probiotics also reduced harm from aflatoxin, a mold toxin that is a potent carcinogen in rats [762]. In addition, probiotics reduced biomarkers of liver cancer risk in humans [763].

Safety

Remember to talk to your doctor before adding a probiotic to your daily regimen.

Most probiotics are considered safe. However, we do not recommend taking probiotics if you are severely ill or immunocompromised. There have been rare incidents of sepsis, endocarditis, and liver abscess during the use of Lactobacilli; additionally, fungemia has been reported with the use of S. boulardii, primarily in patients with severe comorbidities [187].

The most common reported side effects of probiotics are constipation, flatulence, hiccups, nausea, infection, and rash [187].

Some probiotic bacteria can produce biogenic amines: L. brevis and L. lactis can produce tyramine and putrescine [764, 765, 766]. S. thermophilus can produce low amounts of histamine and tyramine [767]. L. reuteri is able to produce histamine [768, 769].

There is at least one case of S. cerevisiae inducing an allergic response [770].

B. bifidum cell-surface biopolymers (BPs) can interact selectively with human serum thyroid peroxidase (TPO) and thyroglobulin (Tg) autoantibodies (anti-TPO and anti-Tg, respectively). There is a possibility that Bifidobacteria play a role in the pathogenesis of autoimmune thyroid diseases (ATD) in those with a genetic predisposition to ATD [771].

Formulation

Probiotic products can be formulated as capsules, tablets, powders (which are regulated as a dietary supplement), and food ingredients (e.g., yogurts, kefirs) [7].

L. acidophilus and B. longum can survive and adhere better to the gastric mucosa than S. thermophilus and B. infantis/adolescentis/bifidum [4].

L. acidophilus can survive a pH of 3 for 3 hours, and L. rhamnosus can survive 4 hours of incubation at pH 2.5. The viability of several strains of Bifidobacterium was maintained for about 3h in the pH range of 1.5 – 3.0. On the other hand, L. delbrueckii and S. thermophilus do not readily survive stomach acidity [4].

To overcome the inability of some probiotics to survive transit through the stomach, microencapsulated or coated probiotic strains have been developed [4].

Furthermore, even though some viable probiotic strains do not survive gastric transit, their dead forms remain beneficial. These nonviable probiotics are now known as ‘para probiotics’ or ‘ghost probiotics’. Non-viable probiotics ameliorated the anti-inflammatory response in rats with colitis, protected against Candida, and prevented the growth of cancer cells [4].

Each probiotic species comes in many different strains. Some of the properties of each species may be strain-specific or vary between strains. You can find information about each strain in the references linked above.

Further Reading

For technical information, check out these individual probiotic chapters:

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About the Author

Biljana Novkovic

Biljana Novkovic

PhD
Biljana received her PhD from Hokkaido University.
Before joining SelfHacked, she was a research scientist with extensive field and laboratory experience. She spent 4 years reviewing the scientific literature on supplements, lab tests and other areas of health sciences. She is passionate about releasing the most accurate science and health information available on topics, and she's meticulous when writing and reviewing articles to make sure the science is sound. She believes that SelfHacked has the best science that is also layperson-friendly on the web.

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