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Probiotics

Fact Sheet for Health Professionals
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Introduction

The International Scientific Association for Probiotics and Prebiotics defines "probiotics" as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host" [1]. These microorganisms, which consist mainly of bacteria but also include yeasts, are naturally present in fermented foods, may be added to other food products, and are available as dietary supplements. However, not all foods and dietary supplements labeled as "probiotics" on the market have proven health benefits.

Probiotics should not be confused with prebiotics, which are typically complex carbohydrates (such as inulin and other fructo-oligosaccharides) that microorganisms in the gastrointestinal tract use as metabolic fuel [2]. Commercial products containing both prebiotic sugars and probiotic organisms are often called "synbiotics." In addition, products containing dead microorganisms and those made by microorganisms (such as proteins, polysaccharides, nucleotides, and peptides) are, by definition, not probiotics.

Identification
Probiotics are identified by their specific strain, which includes the genus, the species, the subspecies (if applicable), and an alphanumeric strain designation [3]. The seven core genera of microbial organisms most often used in probiotic products are Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, Escherichia, and Bacillus. Table 1 shows examples of the nomenclature used for several commercial strains of probiotic organisms.

Table 1: Nomenclature for sample commercial strains of probiotics [3]
Genus Species Subspecies Strain Designation Strain Nickname
Lactobacillus rhamnosus none GG LGG
Bifidobacterium animalis lactis DN-173 010 Bifidus regularis
Bifidobacterium longum longum 35624 Bifantis
 

Mechanisms of action
The human gastrointestinal tract is colonized by many microorganisms, including bacteria, archaea, viruses, fungi, and protozoa. The activity and composition of these microorganisms (collectively known as the gut microbiota, microbiome, or intestinal microflora) can affect human health and disease.

Probiotics exert their effects usually in the gastrointestinal tract, where they may influence the intestinal microbiota. Probiotics can transiently colonize the human gut mucosa in highly individualized patterns, depending on the baseline microbiota, probiotic strain, and gastrointestinal tract region [4].

Probiotics also exert health effects by nonspecific, species-specific, and strain-specific mechanisms [1]. The nonspecific mechanisms vary widely among strains, species, or even genera of commonly used probiotic supplements. These mechanisms include inhibition of the growth of pathogenic microorganisms in the gastrointestinal tract (by fostering colonization resistance, improving intestinal transit, or helping normalize a perturbed microbiota), production of bioactive metabolites (e.g., short-chain fatty acids), and reduction of luminal pH in the colon. Species-specific mechanisms can include vitamin synthesis, gut barrier reinforcement, bile salt metabolism, enzymatic activity, and toxin neutralization. Strain-specific mechanisms, which are rare and are used by only a few strains of a given species, include cytokine production, immunomodulation, and effects on the endocrine and nervous systems. Through all of these mechanisms, probiotics might have wide-ranging impacts on human health and disease.

Because effects of probiotics can be specific to certain probiotic species and strains, recommendations for their use in the clinic or in research studies need to be species and strain specific [3,5,6]. Furthermore, pooling data from studies of different types of probiotics can result in misleading conclusions about their efficacy and safety.

Sources of Probiotics

Food
Fermented foods are made through the growth and metabolic activity of a variety of live microbial cultures. Many of these foods are rich sources of live and potentially beneficial microbes. Some fermented foods, such as sourdough bread and most commercial pickles, are processed after they are fermented and do not contain live cultures in the form in which they are consumed. Many commercial yogurts, another type of fermented food, contain probiotic microorganisms, such as Lactobacillus bulgaricus and Streptococcus thermophilus.

The live microorganisms used to make many fermented foods, including yogurt, typically survive well in the product throughout its shelf life. However, they usually do not survive transit though the stomach and might not resist degradation in the small intestine by hydrolytic enzymes and bile salts and, therefore, might not reach the distal gut [7,8]. However, legitimate probiotic strains contained in yogurt or other foods do survive intestinal transit.

Fermented foods that contain live cultures but do not typically contain proven probiotic microorganisms include many cheeses, kimchi (a Korean fermented cabbage dish), kombucha (a fermented tea), sauerkraut (fermented cabbage), miso (a fermented soybean-based paste), pickles, and raw unfiltered apple cider vinegar made from fermented apple sugars [8].

Certain unfermented foods, such as milks, juices, smoothies, cereals, nutrition bars, and infant and toddler formulas, have added microorganisms. Whether these foods are truly probiotics depends on the microorganism levels they contain when they are eaten, whether they survive intestinal transit, and whether their specific species and strains have health effects.

Dietary supplements
Probiotics are also available as dietary supplements (in capsules, powders, liquids, and other forms) containing a wide variety of strains and doses [9]. These products often contain mixed cultures of live microorganisms rather than single strains. The effects of many commercial products containing "probiotics" have not been examined in research studies, and it is difficult for people not familiar with probiotic research to determine which products are backed by evidence. However, some organizations have systematically reviewed the available evidence and developed recommendations on specific probiotics—including appropriate product, dose, and formulation—to use for preventing or treating various health conditions [3,10].

Probiotics are measured in colony forming units (CFU), which indicate the number of viable cells. Amounts may be written on product labels as, for example, 1 x 109 for 1 billion CFU or 1 x 1010 for 10 billion CFU. Many probiotic supplements contain 1 to 10 billion CFU per dose, but some products contain up to 50 billion CFU or more. However, higher CFU counts do not necessarily improve the product’s health effects.

Current labeling regulations only require manufacturers to list the total weight of the microorganisms on probiotic products’ Supplement Facts labels; this cellular mass can consist of both live and dead microorganisms and, therefore, has no relationship with the number of viable microorganisms in the product [11]. Manufacturers may now voluntarily list the CFUs in a product in addition to total microorganism weight on the Supplement Facts label. Because probiotics must be consumed alive to have health benefits and they can die during their shelf life, users should look for products labeled with the number of CFU at the end of the product’s shelf life, not at the time of manufacture.

Probiotics and Health

The potential health benefits of probiotics are the focus of a great deal of scientific research. This section focuses on research on the use of probiotics to prevent or treat six health conditions: atopic dermatitis, pediatric acute infectious diarrhea, antibiotic-associated diarrhea, irritable bowel syndrome, hypercholesterolemia, and obesity.

Atopic dermatitis
Atopic dermatitis, the most common form of eczema, is also one of the most common chronic inflammatory skin disorders, affecting approximately 15% to 20% of children and 1% to 3% of adults worldwide [12].

Numerous probiotic studies have evaluated the effects of various species and strains of bacteria on the prevention of atopic dermatitis, and several meta-analyses have synthesized the findings of these studies. These studies and meta-analyses show that exposure to probiotics during pregnancy and in early infancy might reduce the risk of developing atopic dermatitis in children. For example, a 2018 meta-analysis included 27 randomized controlled trials (RCTs) and one controlled cohort study in a total of 6,907 infants and children exposed to probiotics in utero for 2 weeks to 7 months (via maternal oral supplementation) and/or by oral administration to the infants after birth for 2 to 13 months [13]. Between ages 6 months and 9 years, probiotic treatment with single strains or mixtures that included Lactobacillus, Bifidobacterium, and Propionibacterium strains significantly reduced the risk of atopic dermatitis from 34.7% in the control group to 28.5% in the probiotic group.

Subgroup analyses showed that the use of probiotics during both the prenatal and postnatal periods significantly reduced the incidence of dermatitis; however, probiotics taken either prenatally only or postnatally only did not. In addition, the effects of probiotic treatment varied by probiotic strain. For example, supplementation with either Lactobacillus rhamnosus or Lactobacillus paracasei significantly reduced the incidence of atopic dermatitis, whereas supplementation with Lactobacillus reuteri or Lactobacillus acidophilus did not.

In contrast, another meta-analysis of 5 randomized clinical trials with a total of 889 participants found that Lactobacillus rhamnosus GG (LGG) supplementation did not reduce the risk of eczema in children up to age 4 years, regardless of the timing of administration (to the mothers during pregnancy and/or during breastfeeding or to the infants directly) [14].

Most published meta-analyses have shown that probiotics slightly reduce atopic dermatitis symptoms in infants and children. For example, a meta-analysis of 13 RCTs with a total of 1,070 participants aged 18 years or younger found that probiotic treatment for 4 to 8 weeks of those with atopic eczema significantly reduced SCORing Atopic Dermatitis (SCORAD) values, indicating reduced symptom severity [15]. Subgroup analyses found probiotics had protective effects in children aged 1 to 18 years (nine trials) but not in infants younger than 1 year (five trials). In addition, treatment with Lactobacillus, Lactobacillus fermentum, or a mixture of probiotic strains, significantly reduced SCORAD values in the children, whereas Lactobacillus rhamnosus GG and Lactobacillus plantarum had no effect.

Another meta-analysis included 8 randomized clinical trials with a total of 741 participants from birth to 36 months of age who were treated with Lactobacillus or Bifidobacterium for 4 to 24 weeks. The results also suggested that probiotics containing Lactobacillus might reduce atopic dermatitis symptoms in infants and toddlers, but those containing Bifidobacterium did not [16]. The treatment significantly improved symptoms in participants with moderate-to-severe forms of the disease but not in those with mild forms. A Cochrane review of 39 RCTs of single probiotics and probiotic mixtures for the treatment of eczema in 2,599 participants aged 1 to 55 years (most were children) found that probiotic treatment might slightly reduce SCORAD scores. However, the researchers concluded that the differences were not clinically significant and that the current evidence does not support the use of probiotics for eczema treatment [17].

Overall, the available evidence suggests that the use of probiotics might reduce the risk of developing atopic dermatitis and lead to significant reductions in atopic dermatitis SCORAD scores, but these products might provide only limited relief from the condition. Furthermore, the effects of probiotics vary by the strain used, the timing of administration, and the patient’s age, so it is difficult to make recommendations.

Pediatric acute infectious diarrhea
Acute diarrhea is usually defined as loose or liquid stools and/or an increase in the frequency of bowel movements (typically at least three in 24 hours) [18]. Acute diarrhea can be accompanied by fever or vomiting, and it usually lasts no more than 7 days.

A Cochrane review of 63 RCTs in a total of 8,014 participants (primarily infants and children) found that single- and multi-strain probiotics significantly shortened the duration of acute infectious diarrhea by about 25 hours. These supplements also decreased the risk that the diarrhea would last 4 or more days by 59% and led to approximately one less bowel movement on the second day in patients who received probiotics compared with patients who did not [19].

An assessment of 11 randomized clinical trials with a total of 2,444 participants showed that Lactobacillus rhamnosus GG is most effective in treating infectious diarrhea at a daily dose of at least 1010 CFU [20,21]. A review of 22 randomized clinical trials with a total of 2,440 participants aged 1 month to 15 years found that Saccharomyces boulardii (most commonly 109 to 1010 CFU/day for 5–10 days) reduced both duration of diarrhea and stool frequency [22]. In both of these analyses, Lactobacillus rhamnosus GG and Saccharomyces boulardii reduced the duration of acute infectious diarrhea by approximately 1 day. However, two subsequent clinical trials found that a 5-day course of LGG (1x1010 CFU twice per day taken alone in one trial and a total of 4x109 CFU twice per day of LGG and L. helveticus R0052 in the other) was no better than placebo at treating or improving the outcomes of acute gastroenteritis in 1,729 infants and small children presenting to pediatric emergency departments [23,24].

Based on a requirement of at least two adequate and well-controlled studies, each convincing on its own, to establish an intervention’s effectiveness, the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition identified two probiotic supplements, Lactobacillus rhamnosus GG (typically at ≥1010 CFU/day for 5–7 days) and Saccharomyces boulardii (typically at 250–750 mg/day [109–1010 CFU] for 5–7 days), for which evidence supported use as adjuncts to rehydration for managing acute infectious diarrhea in pediatric patients [10]. However, recent studies suggest that probiotics might not be efficacious in developed country emergency departments because most episodes of acute infectious diarrhea are self-limiting and require no treatment other than rehydration therapy [23,24]. Therefore, the cost-effectiveness of the use of probiotic supplements to manage acute viral diarrhea lacks consensus [10,19].

Antibiotic-associated diarrhea
Antibiotics are another common cause of acute-onset diarrhea. Antibiotic treatment often disturbs the intestinal microbiome and, by decreasing microbial diversity, can lead to a loss of microbial metabolism (resulting in osmotic diarrhea due to excessive fluid in the intestine), loss of colonization resistance (resulting in increased numbers of infections by other pathogens), and increased intestinal motility [25]. Up to 30% of patients who use antibiotics experience antibiotic-associated diarrhea (AAD) [26].

Individuals receiving inpatient care are at significantly greater risk of developing AAD than individuals receiving outpatient care. Similarly, children younger than 2 years and seniors older than 65 years are at greater risk of developing AAD than other children and adults. Some antibiotics (e.g., erythromycin and penicillin) are associated with AAD more often than others [25,26].

Meta-analyses indicate that the use of any of a few species and strains (described below) of probiotics might reduce the risk of AAD by 51% [27]. However, the benefits of probiotic use to prevent AAD depend on the type of antibiotic that caused the AAD, the strain(s) of probiotic used, the life stage of the user (child, younger adult, or older adult), and whether the user is receiving inpatient or outpatient care. Positive associations between intakes of probiotics and reduced risk of AAD have been found in children and adults aged 18 to 64 years but not in adults aged 65 years and older [28].

Both Lactobacillus rhamnosus GG and Saccharomyces boulardii have been shown to reduce the risk of AAD. In a systematic review and meta-analysis of 12 RCTs with a total of 1,499 children and adults, treatment with Lactobacillus rhamnosus GG (4 x 108 to 12 x 1010 CFU) compared with placebo or no additional treatment for 10 days to 3 months reduced the risk of AAD in patients treated with antibiotics from 22.4% to 12.3% [29]. However, when the 445 children and 1,052 adults were evaluated separately, the difference was statistically significant in children only. Although the optimal dose of Lactobacillus rhamnosus GG is unclear, 1 to 2 x 1010 CFU/day reduced AAD risk in children by 71% [29]. Taking probiotics within 2 days of the first antibiotic dose is more effective than starting to take them later.

In a systematic review and meta-analysis of 21 RCTs in a total of 4,780 participants, treatment with Saccharomyces boulardii compared with placebo or no treatment reduced the risk of AAD in 3,114 adults treated with antibiotics from 17.4% to 8.2% [29]. In the 1,653 children in this study, Saccharomyces boulardii reduced the risk from 20.9% to 8.8%. Various doses of Saccharomyces boulardii were tested, and no clear dose-dependent effects were observed.

Overall, the available evidence suggests that starting probiotic treatment with Lactobacillus rhamnosus GG or Saccharomyces boulardii within 2 days of the first antibiotic dose helps reduce the risk of AAD in children and adults aged 18 to 64, but not in elderly adults. There is no evidence to suggest that the benefits are greater when more than one probiotic strain is used.

Irritable bowel syndrome
Irritable bowel syndrome (IBS) is a common functional disorder of the gastrointestinal tract characterized by recurrent abdominal discomfort or pain, bloating, and changes in stool form or frequency. Although the causes of IBS are not completely understood, growing evidence suggests potential roles for intestinal microbiota in its pathophysiology and symptoms; IBS has also been linked to stress [30]. According to this research, proinflammatory bacterial species, including Enterobacteriaceae, are abundant in patients with IBS, who typically also have a corresponding reduction in amounts of Lactobacillus and Bifidobacterium [31]. Probiotic products commonly contain Lactobacillus and Bifidobacterium and, therefore, have the potential to restore some missing microbial functionality and, consequently, help manage IBS symptoms.

Several meta-analyses have assessed the role of probiotics in patients with IBS [32-36]. Most have found that probiotics have a positive, although modest, beneficial effect. For example, a meta-analysis of 23 RCTs in a total of 2,575 patients found that, overall, probiotics reduced the risk that IBS symptoms would persist or not improve by 21% [32]. Various species and strains of probiotics had beneficial effects on global IBS symptoms, abdominal pain, bloating, and flatulence scores, but the quality of the studies was low. Some combinations of probiotics were superior to individual strains in this analysis, but no specific combination was superior to another. A second meta-analysis of 15 randomized- controlled trials in a total of 1,793 patients with IBS found that probiotics reduced overall symptoms and abdominal pain more than placebo after 8 to 10 weeks of therapy; in children, these supplements also improved mucosal barrier function [33].

A more recent systematic review included 35 RCTs of 16 single-strain and 19 multi-strain products in 3,406 adults with IBS [37]. Of the studies that found a statistically significant reduction in global symptoms (14 of 29 trials) or a clinically meaningful reduction in abdominal pain (8 of 34 trials), most used multi-strain probiotic products. Furthermore, only trials of multi-strain products found a clinically meaningful improvement in quality of life [34,35].

Whether different strains of probiotic bacteria have beneficial effects on IBS probably depends on the IBS symptom being evaluated [38]. In a meta-analysis of 10 RCTs with a total of 877 adults treated with probiotics or placebo for 4 weeks to 6 months, pain scores improved significantly with administration of probiotics containing Bifidobacterium breve, Bifidobacterium longum, or Lactobacillus acidophilus species compared with placebo treatment [39]. In contrast, Streptococcus salivarius ssp. thermophilus, Bifidobacterium animalis, Bifidobacterium infantis, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus bulgaricus, and Saccharomyces boulardii had no significant effect. The abdominal distension scores improved with use of probiotics containing Bifidobacterium breve, Bifidobacterium infantis, Lactobacillus casei, or Lactobacillus plantarum species. Flatulence declined with use of all tested probiotics, but the studies showed no positive effect of probiotics on quality of life.

Overall, the available evidence indicates that probiotics might reduce some symptoms of IBS. However additional high-quality clinical trials are needed to confirm the specific strain, dose, and duration of treatment required as well as the type of IBS (such as with predominant diarrhea or constipation) that can be treated effectively with probiotics.

Hypercholesterolemia
High levels of cholesterol in the blood or cholesterol trapped in arterial walls are a risk factor for cardiovascular disease (CVD). Low-density lipoprotein (LDL) carries cholesterol to tissues and arteries. The higher the LDL level, the greater the risk is for CVD. High-density lipoprotein (HDL) carries cholesterol from the tissues to the liver and leads to its excretion. A low level of HDL increases a person’s risk of CVD.

Researchers have studied the use of probiotics to improve lipid profiles. The mechanisms of their effects on cholesterol concentrations include catabolism of cholesterol by increasing:

  • Bile salt hydrolase activity, which increases the need for new bile acids and thus reduces serum cholesterol levels [40-42];
  • Binding of cholesterol in the small intestine, which reduces the amount that the body absorbs;
  • Assimilation and incorporation of cholesterol into bacteria [42], thus lowering cholesterol levels in blood;
  • Production by lactobacilli and bifidobacteria of short-chain fatty acids, which lower hepatic cholesterol synthesis and regulate cholesterol metabolism [40-43].

A meta-analysis of 30 RCTs with 1,624 participants (mostly adults aged 18 years or older) demonstrated that those treated with probiotics for 3 to 12 weeks had 7.8 mg/dL lower total cholesterol and 7.3 mg/dL lower LDL cholesterol concentrations than those treated with placebo [44]. In subgroup analyses, the benefits of probiotics were slightly greater in studies that lasted 8 weeks or longer and in participants who had baseline cholesterol levels higher than 240 mg/dL. Among the strains included in more than three studies, Lactobacillus acidophilus, a mixture of Lactobacillus acidophilus and Bifidobacterium lactis, and Lactobacillus plantarum were associated with significant reductions in total and LDL cholesterol concentrations, but Lactobacillus helveticus and Enterococcus faecium were not. In a smaller meta-analysis of 11 RCTs in 602 adults with normal or high cholesterol levels, those treated with probiotics for 2 to 10 weeks had 6.6 mg/dL lower total cholesterol and 8.5 mg/dL lower LDL cholesterol levels than those treated with placebo, but the probiotic treatment had no significant effects on HDL cholesterol levels [45]. The effects were most pronounced with consumption of probiotics for more than 4 weeks by participants with hypercholesterolemia and those aged 45 or older. In both meta-analyses, participants included both healthy adults and adults with hypercholesterolemia, CVD, diabetes, or obesity.

However, the authors of a more recent review of the influence of probiotics on blood lipid profiles of healthy adults (in 14 studies with a total of 942 adults treated from 15–150 days) found insufficient evidence to conclude that probiotics improve blood lipid levels [46]. Another review found that use of probiotics containing multiple strains produced statistically significant reductions in total and LDL cholesterol levels (by 12.0 and 20.1 mg/dL, respectively), whereas trials that used a single strain did not [47].

Overall, research suggests that the use of multiple probiotic strains in combination as well as of probiotics containing Lactobacillus acidophilus, a mixture of Lactobacillus acidophilus and Bifidobacterium lactis, or Lactobacillus plantarum might reduce total and LDL cholesterol levels. However, more research is needed to confirm these findings.

Obesity
The gut microbiota play an important role in nutrient and energy extraction from food. Research in mice suggests that the gut microbiota affect not only use of energy from the diet, but also energy expenditure and storage within the host [48]. Whether these effects translate to humans is unknown.

Results of clinical trials that assessed the impact of probiotics on obesity-related endpoints have been inconsistent. One 12-week clinical trial, for example, randomized 210 healthy adults aged 35 to 60 years who had large amounts of visceral fat to consume 200 g/day fermented milk containing 107, 106, or 0 (control) CFU of Lactobacillus gasseri SBT2055 (LG2055) per gram of milk [49]. Participants who received 107 or 106 CFU/g milk of Lactobacillus gasseri experienced significant reductions in visceral fat area (mean reductions of 8.5% and 8.2%, respectively), body mass index, waist and hip circumference, and body fat mass compared with the control group. In another randomized clinical trial, daily supplementation with 3.24 x 108 CFU Lactobacillus rhamnosus CGMCC1.3724 for 24 weeks combined with an energy-restricted diet for the first 12 weeks (500 kcal/day less than estimated calorie needs) did not significantly affect weight loss compared with placebo in 125 obese adults aged 18 to 55 years [50]. However, the Lactobacillus supplementation did significantly reduce body weight after 12 weeks (loss of 1.8 kg) and 24 weeks (loss of 2.6 kg) compared with placebo in the 77 female participants.

A 2017 systematic review of 14 clinical trials, including the two described above, in 1,067 overweight or obese individuals showed that probiotics (mostly Lactobacillus administered at various doses for 3 weeks to 6 months) significantly decreased body weight and/or body fat in nine trials, had no effect in three trials, and increased body weight in two trials [51]. Another recent systematic review and meta-analysis of 15 RCTs in 957 overweight or obese individuals found that supplementation with various doses and strains of probiotics for 3 to 12 weeks resulted in larger reductions in body weight (by 0.6 kg), body mass index (by 0.27 kg/m2), and fat percentage (by 0.6%) than placebo [52]. However, these effects were small and of questionable clinical significance.

In contrast, the most recent systematic review and meta-analysis, which included 19 randomized trials in 1,412 participants, found that supplementation with probiotics or synbiotics reduced waist circumference slightly (by 0.82 cm) but had no effect on body weight or body mass index, although the quality of evidence was low to moderate [53]. The findings from another meta-analysis of 14 trials in 881 adults, 5 trials in 726 children, and 12 trials in 1,154 infants suggested that probiotics promote loss of a mean of 0.54 kg in adults, gain of a mean of 0.20 kg in children, and no significant weight loss or gain in infants [54].

Taken together, these results indicate that the effects of probiotics on body weight and obesity might depend on several factors, including the probiotic strain, dose, and duration, as well as certain characteristics of the user, including age, sex, and baseline body weight. Additional research is needed to understand the potential effects of probiotics on body fat, body weight, and obesity in humans.

Safety Considerations

Many probiotic strains derive from species with a long history of safe use in foods or from microorganisms that colonize healthy gastrointestinal tracts. For these reasons, the common probiotic species—such as Lactobacillus species (acidophilus, casei, fermentum, gasseri, johnsonii, paracasei, plantarum, rhamnosus, and salivarius) and Bifidobacterium species (adolescentis, animalis, bifidum, breve, and longum)—are unlikely to cause harm [3].

Given the large quantities of probiotics consumed around the world, the numbers of opportunistic infections that result from currently marketed probiotics are negligible. For example, probiotics have been administered to thousands of newborn infants, including some who were premature, without a single case of sepsis [55]. However, some clinical trials of probiotics are not designed to adequately address questions about safety, leaving gaps in available safety evidence [56-58].

Side effects of probiotics are usually minor and consist of self-limited gastrointestinal symptoms, such as gas. In a few cases, mainly involving individuals who were severely ill or immunocompromised, the use of probiotics has been linked to bacteremia, fungemia (fungi in the blood), or infections that result in severe illness [59,60]. However, some case reports did not confirm that the specific strain of probiotics used was the cause of the infection. In other cases, the probiotic strain used was confirmed to be the opportunistic pathogen. Because species used as probiotics can be normal residents of a patient’s microbiota, such confirmation is important.

At least 60 reports have been published since 1966 of fungemia associated with the use of probiotics containing the yeast Saccharomyces cervisiae. In many of these cases, the patients were in an intensive care unit, were receiving enteral or parenteral nutrition, had a central venous catheter, or had received broad-spectrum antimicrobial treatment [61]. However, a Finnish study that tracked Lactobacillus-induced bacteremia (bacteria in the blood) showed that increased use of the probiotic Lactobacillus rhamnosus GG did not lead to increased rates of bacteremia [62].

For individuals with compromised immune function or other serious underlying diseases, the World Gastroenterology Organisation (WGO) advises restricting probiotic use to the strains and indications that have proven efficacy [3].

Probiotic Selection and Use

Expert bodies of health professionals make no recommendations for or against probiotic use by healthy people. For people with various health conditions, however, published studies and reviews provide some guidance (as described above) on probiotic species, strains, and doses that might alleviate their symptoms.

The WGO notes that the optimal dose of probiotics depends on the strain and product. The organization therefore recommends that clinicians who advise their patients to use probiotics specify the probiotic strains, doses, and duration of use that studies in humans have shown to be beneficial [3]. The WGO guidelines include a summary of evidence on specific probiotic strains used in studies for specific gastrointestinal endpoints [3]. Finally, the WGO recommends that probiotic supplement users check the labels of probiotic supplements for recommended storage conditions; for example, some require refrigeration, whereas others can be stored at room temperature.

The International Scientific Association for Probiotics and Prebiotics advises manufacturers to list the total number of CFUs—ideally for each strain—on the "expiration" or "use by" date on the product label [63]. The association also suggests that consumers of these supplements avoid products that list the number of CFUs "at time of manufacture" because this information does not account for declines in CFUs over a product’s lifespan.

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Disclaimer

This fact sheet by the Office of Dietary Supplements (ODS) provides information that should not take the place of medical advice. We encourage you to talk to your healthcare providers (doctor, registered dietitian, pharmacist, etc.) about your interest in, questions about, or use of dietary supplements and what may be best for your overall health. Any mention in this publication of a specific product or service, or recommendation from an organization or professional society, does not represent an endorsement by ODS of that product, service, or expert advice.

Updated: May 1, 2019