This is a fact sheet intended for health professionals. For a general overview, see our consumer fact sheet.
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 present in some fermented foods (e.g., yogurt), are added to certain food products, and are available as dietary supplements. However, not all foods and dietary supplements that are labeled as probiotics 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 prebiotics and probiotic microorganisms are often called synbiotics. Probiotics should also not be confused with postbiotics, which are preparations comprised of dead, intact, or fragmented microorganisms, with or without their metabolites, that confer a health benefit on the host [3].
Identification
Probiotics are identified by their genus, species, and strain designation; some probiotics also receive subspecies names. Probiotic products often contain microbial organisms from the genera Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, Escherichia, and Bacillus and from the family Lactobacillaceae.
Probiotics are identified by their specific strain, which includes the genus, the species, the subspecies (if applicable), and an alphanumeric strain designation [4]. Microbial organisms from the genera Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, Escherichia, and Bacillus are commonly used in probiotic products. In addition, products commonly contain microbes from the family Lactobacillaceae, which includes several species that were formerly in the Lactobacillus genus before that genus was restructured in 2020 [5]. When reporting the results from specific studies, this fact sheet maintains the original genus names that were in use at the time the research was conducted. Table 1 shows examples of the nomenclature used for several commercial strains of probiotic organisms.
Table 1: Nomenclature for sample commercial strains of probiotics [4]
| Genus |
Species |
Subspecies |
Strain Designation |
Strain Nickname |
| Lacticaseibacillus(formerly Lactobacillus) |
rhamnosus |
None |
GG |
LGG |
| Bifidobacterium |
animalis |
lactis |
DN-173 010 |
Bifidus regularis |
| Bifidobacterium |
longum |
longum |
35624 |
Bifantis |
Mechanisms of action
Probiotics exert their health effects through a wide variety of mechanisms. Some of these mechanisms, such as inhibiting the growth of pathogenic microorganisms in the gastrointestinal tract, are widely shared among probiotic strains. Other mechanisms are unique to a particular species or strain.
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 are consumed orally and exert their effects in the gastrointestinal tract, where they may influence the intestinal microbiota. Probiotics may transiently colonize the human gut mucosa in highly individualized patterns, depending on the baseline microbiota, probiotic strain, and gastrointestinal tract region [6].
Probiotics also exert health effects by nonspecific, species-specific, and strain-specific mechanisms. The nonspecific mechanisms vary widely among the strains, species, or even genera of commonly used probiotic supplements. These mechanisms include the inhibition of the growth of pathogenic microorganisms in the gastrointestinal tract (by fostering colonization resistance, improving intestinal transit, producing antimicrobial substances, or helping normalize a perturbed microbiota), production of bioactive metabolites (e.g., short-chain fatty acids), and the reduction of luminal pH in the colon [1]. Species-specific mechanisms can include vitamin synthesis, gut barrier reinforcement, bile salt metabolism, enzymatic activity, and toxin neutralization. Other mechanisms, such as cytokine production, specific immunomodulatory activities, and effects on the endocrine and nervous systems, are expressed in a strain-specific manner.
Because the effects of probiotics can be specific to certain probiotic strains, recommendations for their use in the clinic need to be strain-specific [4,7,8]. Additionally, researchers should take probiotic strains into account when designing studies and when pooling data from studies that may have used different probiotic strains to avoid misleading conclusions about their efficacy and safety.
Sources of Probiotics
Food
Some types of fermented foods, such as yogurt, are potential sources of beneficial microbes, though not all fermented foods that contain live cultures have probiotic microorganisms. Probiotic microorganisms are also sometimes added to unfermented foods.
Fermented foods are made through the growth and metabolic activity of a variety of live microbial cultures [9]. 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 when consumed. Yogurt, another type of fermented food, is made using Lactobacillus bulgaricus and Streptococcus thermophilus. Yogurt may also contain probiotic microorganisms from Bifidobacterium or Lactobacillaceae.
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 [10].
Certain unfermented foods, such as milks, juices, smoothies, cereals, nutrition bars, and infant and toddler formulas, might be formulated with added probiotics. Typically, these probiotics are indicated on the label, with a strain designation and the number of viable microorganisms.
Dietary supplements
Dietary supplements that contain probiotics can include from one to many strains. The number of viable cells in a probiotic supplement is indicated by the number of colony-forming units (CFU) listed on the label. However, it can be difficult to determine which products offer verifiable health benefits due to the wide variety of probiotic strains and doses found in probiotic products and inconsistent labeling practices and recommendations for use.
Probiotics are available as dietary supplements (in capsules, powders, liquids, and other forms) that contain a wide variety of strains and doses [11]. Products can include single strains or multiple strains of live microorganisms. The effects of many commercial products that contain probiotics have not been examined in research studies, and it is difficult for people who are not familiar with probiotic research to determine which products are backed by evidence [12]. However, some organizations have systematically reviewed the available evidence and developed recommendations for using specific probiotics—including the appropriate product, dose, and formulation—to prevent or treat various health conditions [4,13].
Probiotics are measured in 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 50 billion CFU or more. However, products with higher CFU counts are not necessarily more effective than products with a lower CFU count.
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 [14]. Manufacturers may voluntarily list the CFU in a product in addition to the 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 eight health conditions: atopic dermatitis, pediatric acute infectious diarrhea, antibiotic-associated diarrhea (AAD), necrotizing enterocolitis (NEC), inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), hypercholesterolemia, and obesity.
For information on probiotics and the common cold, influenza, and other respiratory tract infections, please see the Office of Dietary Supplements (ODS) health professional fact sheet, Dietary Supplements for Immune Function and Infectious Diseases.
Atopic dermatitis
Studies have evaluated the use of various probiotic products to prevent atopic dermatitis, a common inflammatory skin disorder. The results of these studies suggest that probiotics may reduce the risk of developing atopic dermatitis and the severity of symptoms, though the relief these products can provide may be limited.
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 [15].
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 who were 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 [16]. The results showed that between age 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, taking probiotics during only the prenatal or postnatal period did not. In addition, the effects of probiotic treatment varied by 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 five RCTs 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 whether the children received probiotics directly or were exposed to probiotics in utero and/or during breastfeeding via maternal supplementation [17].
Most published meta-analyses have shown that probiotics slightly reduce the severity of atopic dermatitis symptoms in infants and children. For example, a meta-analysis of 13 RCTs with a total of 1,070 participants age 18 years or younger found that probiotic treatment for 4 to 8 weeks significantly reduced SCORing Atopic Dermatitis (SCORAD) values, indicating reduced symptom severity [18]. Subgroup analyses found that probiotics had protective effects in children age 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 LGG and Lactobacillus plantarum had no effect.
Another meta-analysis included eight RCTs 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 [19]. Probiotics that contained Lactobacillus reduced the severity of atopic dermatitis symptoms in infants and toddlers, but those containing Bifidobacterium did not. In addition, 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 that were used to treat eczema in 2,599 participants age 1 to 55 years (most were children) found that probiotic treatment might slightly reduce SCORAD scores [20]. 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.
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
Some evidence supports using certain probiotics to manage acute infectious diarrhea in pediatric patients; a few reviews have shown that some probiotics reduce the duration of acute diarrhea. However, not all trials concur with these results, and it is unclear whether probiotic supplements are an effective method for managing this condition in developed countries.
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) [21]. Acute diarrhea can be accompanied by fever or vomiting, and it usually lasts no more than 7 days.
A 2020 Cochrane Review that included 82 RCTs with a total of 12,127 participants (primarily children) reported a reduction of 36% in the risk of diarrhea that lasted 48 hours or more in people who received probiotics compared with those who did not [22]. Probiotics also reduced the mean duration of diarrhea by 21.3 hours. However, the authors noted that there was significant heterogeneity between the included studies, and when they included only studies that had a low risk of bias in their analysis, they found no difference between groups for the risk of diarrhea that lasted 48 hours or more or for the duration of diarrhea.
An assessment of 11 RCTs with a total of 2,444 participants showed that LGG is most effective in treating infectious diarrhea at a daily dose of at least 1010 CFU [23,24]. A review of 22 RCTs and non-randomized trials with a total of 2,440 participants age 1 month to 15 years found that administering Saccharomyces boulardii (most commonly 109 to 1010 CFU/day for 5–10 days) reduced both the duration of diarrhea and stool frequency [25]. In both of these analyses, LGG 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 (1 x 1010 CFU twice per day taken alone in one trial and a total of 4 x 109 CFU twice per day of LGG and Lactobacillus helveticus R0052 in the other) was no better than placebo at treating or improving the outcomes of acute gastroenteritis in 1,729 infants and young children who presented to pediatric emergency departments [26,27].
Recent studies suggest that probiotics might not be efficacious in emergency departments in developed countries because most episodes of acute infectious diarrhea are self-limiting and require no treatment other than rehydration therapy [26,27]. Therefore, the cost-effectiveness of using probiotic supplements to manage acute viral diarrhea lacks consensus [28,29].
In 2023, the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Working Group on Probiotics and Prebiotics issued updated versions of their recommendations for using probiotics to manage specific gastrointestinal disorders in children, including acute gastroenteritis [30]. The Working Group reported that there is evidence that LGG, Saccharomyces boulardii, Limosilactobacillus reuteri, and the combination of Lacticaseibacillus rhamnosus and Limosilactobacillus reuteri can reduce the duration of diarrhea; therefore, they recommend the use of specific doses and durations of these probiotics in pediatric patients with acute gastroenteritis. However, the grade of recommendation for each of these probiotics was weak, and the certainty of evidence for each was low or very low. In contrast, the American Gastroenterological Association (AGA) recommended against the use of probiotics in children with acute infectious gastroenteritis in the United States and Canada in their 2020 technical review [31]. In this review, most of the studies that showed a benefit were performed in India, Italy, Poland, Turkey, and Pakistan, and the review authors cited concerns about the risk of bias in these studies. The few studies that were conducted in the United States and Canada reported no benefits.
Antibiotic-associated diarrhea
Antibiotics can disrupt the intestinal microbiome, and people who are taking antibiotics are at risk of antibiotic-associated diarrhea (AAD). Some systematic reviews and meta-analyses report that starting certain probiotic treatments within 2 days of the first antibiotic dose helps reduce the risk of antibiotic-associated diarrhea in specific patient populations.
Antibiotics are another common cause of acute-onset diarrhea. By decreasing microbial diversity, antibiotic treatment often disturbs the intestinal microbiome and 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 [32]. Up to 30% of patients who use antibiotics experience AAD [33].
Individuals who are receiving inpatient care are at significantly greater risk of developing AAD than those who are 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, penicillin) are associated with AAD more often than others [32,33].
Meta-analyses indicate that the use of any of a few species and strains of probiotics might reduce the risk of AAD by 51% [34]. However, the benefits of using probiotics 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 (i.e., child, younger adult, older adult), and whether the user is receiving inpatient or outpatient care. The use of probiotics has been associated with a reduced risk of AAD in children and adults age 18 to 64 years but not in adults age 65 years and older [35].
Both LGG and Saccharomyces boulardii have been shown to reduce the risk of AAD. In a systematic review and meta-analysis of 12 RCTs that included a total of 1,499 children and adults, treatment with 4 x 108 to 12 x 1010 CFU LGG for 10 days to 3 months reduced the risk of AAD in patients who were treated with antibiotics from 22.4% to 12.3% [36]. However, when the 445 children and 1,052 adults were evaluated separately, the difference was only statistically significant in children. Although the optimal dose of LGG is unclear, 1 to 2 x 1010 CFU/day reduced the risk of AAD in children by 71% [36]. 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 that enrolled a total of 4,780 adults and children (who were mostly between 6 months and 65 years of age), treatment with Saccharomyces boulardii reduced the risk of AAD in adults who were treated with antibiotics from 17.4% to 8.2% when compared with placebo or no treatment [37]. Among the children, 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.
A 2023 position paper from the ESPGHAN Working Group on Probiotics and Prebiotics recommends administering doses of 5 x 109 CFU/day or more of LGG or Saccharomyces boulardii starting simultaneously with antibiotics to prevent AAD in nonhospitalized and hospitalized children who have risk factors for AAD, such as the presence of comorbidities [30].
Overall, the available evidence suggests that starting probiotic treatment with LGG or Saccharomyces boulardii within 2 days of the first antibiotic dose helps reduce the risk of AAD in children and adults age 18 to 64. There is no evidence to suggest that the benefits are greater when more than one probiotic strain is used.
Necrotizing enterocolitis
Researchers have evaluated whether specific combinations of probiotics can reduce the severe inflammatory responses seen in preterm infants with necrotizing enterocolitis (NEC). Probiotic products are sometimes used in hospital settings to reduce the risk of necrotizing enterocolitis, but the U.S. Food and Drug Administration has raised concerns that administering probiotics to preterm infants may cause adverse effects.
NEC is a life-threatening gastrointestinal illness that mostly affects preterm infants within the first few weeks of birth. NEC occurs when an imbalance in the communities of bacteria in the intestine provokes an inflammatory response from the body; the resulting inflammation can destroy the cells that line the intestine. The risk of NEC is especially high in preterm infants with very low birth weight (i.e., those weighing <1,500 g [3.3 pounds]) [38]. Infants who recover from NEC may have long-lasting health problems, including short bowel syndrome, parenteral nutrition-associated liver injury, and developmental delays.
Certain probiotics can block the signaling pathways in the cells of the intestine that respond to bacterial invaders [38,39]. This can potentially protect the intestine by reducing the inflammatory response. Other probiotics may strengthen the gut barrier, reducing the risk of bacterial translocation and sepsis [40-43]. Thus, researchers have investigated the use of probiotics to prevent NEC in preterm infants, and probiotic products are sometimes used in hospital settings to reduce the risk of NEC [44-46].
In a 2020 AGA technical review, the authors analyzed the results of 63 trials that evaluated the use of single-strain and multi-strain probiotics in a total of 15,712 preterm infants (<37 weeks gestational age) [47]. The review found that administering specific combinations of Lactobacillus and Bifidobacterium strains reduced the risk of all-cause mortality, the risk of severe NEC, and the number of days to reach full enteral feeds in these infants when compared with placebo. The results of this review informed AGA’s clinical practice guidelines for probiotics, in which AGA recommends using specific combinations of Lactobacillus and Bifidobacterium strains in preterm, low-birth-weight infants to prevent NEC [31]. In addition, the World Health Organization published guidelines in 2023 for the care of preterm or low birth weight infants [48]. Their guidelines state that probiotics may be considered for human-milk-fed preterm infants who are born before 32 weeks gestation. Also in 2023, a systematic review of 90 trials in preterm infants found that multi-strain probiotics reduce the risk of all-cause mortality, severe NEC, and feeding intolerance; multi-strain probiotics also reduce the time needed to reach full enteral feeds and the duration of hospitalization [49]. However, a Cochrane Review stated that the available evidence for using probiotics in very preterm infants born before 32 weeks gestation and very low birth weight infants who weigh less than 1,500 g at birth is inconclusive and called for more research in this population [46].
In their 2023 position paper, the ESPGHAN Working Group on Probiotics and Prebiotics revisited their 2020 recommendations [50] for using probiotics to prevent NEC in preterm infants and concluded that no changes to the 2020 recommendations were needed [30]. They continue to recommend using either LGG (1 to 6 × 109 CFU) or the combination of Bifidobacterium infantis, Bifidobacterium lactis, and Streptococcus thermophilus (3.0 to 3.5 × 108 CFU for each strain) to reduce the risk of NEC in preterm infants. However, they stated that the grade of this recommendation is weak and the certainty of evidence is low. In addition, they noted that all safety and quality issues must be addressed, such as the potential for probiotic sepsis in preterm infants and the fact that probiotic products might not be labeled with the correct strains [30,50].
The U.S. Food and Drug Administration (FDA) issued a news release in 2023 informing the public, including health care providers, that administering probiotics to preterm infants may cause infection or invasive and potentially fatal disease [51]. FDA reported that probiotics have been associated with one infant death and more than two dozen other adverse events in recent years, and the agency reiterated the fact that probiotics have not undergone FDA’s premarket process to evaluate their safety, effectiveness, and quality for medical uses. The agency called for more rigorous clinical trials to provide better evidence for using probiotics in infants.
Inflammatory bowel disease
Alterations to the gut microbiome may play a role in inflammatory bowel disease (IBD), and researchers are evaluating whether probiotics can help manage this chronic condition. The results have been mixed; studies have reported that certain probiotics might provide some benefits to people with ulcerative colitis but not to those with Crohn’s disease. Clinical practice guidelines do not specifically recommend the use of probiotics in people with IBD.
IBD is a chronic inflammatory disease that includes ulcerative colitis and Crohn’s disease [52]. The exact cause of IBD is unknown, but it is probably a combination of inherited and environmental factors, including genetic alterations and immune system dysfunction [47]. Various treatments for IBD, including oral steroids and other medications, are available, but no cure exists.
Researchers are exploring whether individuals with IBD have alterations in the gut microbiome and whether probiotics might help manage IBD [31]. Several reviews have assessed the effects of probiotics on IBD [31,47,53-56]. The authors of all of these reviews reached similar conclusions—that certain probiotics might have modestly beneficial effects on ulcerative colitis but not Crohn’s disease.
A 2020 systematic review from AGA examined the role of probiotics in managing gastrointestinal disorders [47]. The review included 12 trials that used probiotics to induce or maintain remission in 689 children and adults with Crohn’s disease as well as 17 trials that examined the use of various probiotic formulations to induce or maintain remission in 1,673 children and adults with ulcerative colitis. The trials used various probiotic strains and combinations—including Saccharomyces boulardii, LGG, Lactobacillus johnsonii NCC 533, Escherichia coli Nissle 1917, and an eight-strain combination product called VSL#3—for several months. The results provided no evidence that probiotics help induce or maintain remission in children or adults with Crohn’s disease. The authors could not draw conclusions about whether probiotics benefit patients with severe ulcerative colitis or are effective alternatives to existing therapies. However, there is some evidence to suggest that these supplements might modestly reduce disease activity in individuals with mild-to-moderate ulcerative colitis when combined with conventional therapies. The results of this review are limited by the differences between the studies, including different patient populations, probiotic formulations, treatment durations, and concomitant therapies.
A 2020 Cochrane Review of 14 studies that enrolled a total of 865 participants with ulcerative colitis also indicated that probiotics may help induce remission and that combining probiotics with 5-ASA (an anti-inflammatory medication commonly used to treat IBD) may be superior to using 5-ASA alone [57]. However, the evidence was limited and of low certainty. A similar 2020 Cochrane Review of 12 studies in 1,473 participants with ulcerative colitis examined whether probiotics can help maintain remission [58]. The authors concluded that the effects of products are uncertain because of the small number of participants in the studies and the unreliable methodologies used.
An AGA clinical decision support tool makes no recommendation on the use of probiotics in adults and children with IBD due to knowledge gaps [59]. Similarly, in a clinical practice guideline on the role of probiotics in managing gastrointestinal disorders, AGA recommends using probiotics in adults and children with ulcerative colitis or Crohn’s disease only in the context of a clinical trial [31]. Consensus guidelines published by the British Society of Gastroenterology in 2019 addressed the management of IBD, including the use of probiotics [56]. The authors concluded that although probiotics may be modestly beneficial for people with ulcerative colitis, they should not be routinely used. For people with Crohn’s disease, the authors found no evidence of any benefit. In 2023, the ESPGHAN Working Group on Probiotics and Prebiotics stated that there was not enough evidence to recommend for or against the use of probiotics in children with ulcerative colitis or Crohn’s disease [30].
Additional research, including well-powered RCTs, is needed to identify which patients with IBD might benefit from probiotics and which probiotic strains are most effective [31,54].
Irritable bowel syndrome
In people with irritable bowel syndrome (IBS), populations of Lactobacillus and Bifidobacterium decrease as populations of proinflammatory bacterial species increase. Certain probiotic products have the potential to restore some missing microbial functionality and help manage the symptoms of this condition.
IBS is a common functional disorder of the gastrointestinal tract that is 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 [60]. According to this research, proinflammatory bacterial species, including Enterobacteriaceae, are abundant in patients with IBS, who typically also have a corresponding reduction in the amounts of Lactobacillus and Bifidobacterium in the gastrointestinal tract [61]. 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 [62-66]. 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% [62]. 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 RCTs in a total of 1,793 patients with IBS found that probiotics reduced the severity of overall symptoms and abdominal pain more than placebo after 8 to 10 weeks of therapy; in children, these supplements also improved mucosal barrier function [63].
A more recent systematic review included 35 RCTs of 16 single-strain and 19 multi-strain products in 3,406 adults with IBS [67]. 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 [64,65].
Whether different strains of probiotic bacteria have beneficial effects in people with IBS probably depends on the IBS symptom being evaluated [68]. In a meta-analysis of 10 RCTs that enrolled a total of 877 adults who were treated with probiotics or placebo for 4 weeks to 6 months, people who received probiotics that contained Bifidobacterium breve, Bifidobacterium longum, or Lactobacillus acidophilus species had lower pain scores than those who received placebo [69]. In contrast, Streptococcus salivarius ssp. thermophilus, Bifidobacterium animalis, Bifidobacterium infantis, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus bulgaricus, and Saccharomyces boulardii had no significant effect. Flatulence declined with the use of all tested probiotics, and the abdominal distension scores improved with the use of probiotics that contained Bifidobacterium breve, Bifidobacterium infantis, Lactobacillus casei, or Lactobacillus plantarum species. The authors noted that, overall, the studies showed no clear positive effect of probiotics on quality of life.
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
Some studies have suggested that taking combinations of certain probiotic strains may improve lipid profiles. Specifically, the use of specific probiotics may reduce total and low-density lipoprotein cholesterol levels. However, study results have been mixed, and more research is needed.
High levels of cholesterol in the blood or cholesterol trapped in arterial walls are risk factors 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 [70-72]
- The binding of cholesterol in the small intestine, which reduces the amount that the body absorbs
- The assimilation and incorporation of cholesterol into bacteria [72], thus lowering cholesterol levels in blood
- The production of short-chain fatty acids by lactobacilli and bifidobacteria, which lowers hepatic cholesterol synthesis and regulates cholesterol metabolism [70-73]
A meta-analysis of 30 RCTs with 1,624 participants (mostly adults age 18 years or older) found that administering probiotics for 3 to 12 weeks reduced total cholesterol concentrations by a mean of 7.8 mg/dL and reduced LDL concentrations by a mean of 7.3 mg/dL compared with placebo [74]. In subgroup analyses, the benefits of probiotics were slightly greater in studies that lasted 8 weeks or longer and in participants who had baseline total 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 [75]. The effects were most pronounced in people who consumed probiotics for more than 4 weeks, in those with hypercholesterolemia, and in those age 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 the blood lipid profiles of healthy adults (in 14 studies with a total of 942 adults treated for 15–150 days) found insufficient evidence to conclude that probiotics improve blood lipid levels [76]. Another review found that the use of probiotics that contained 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 [77].
Overall, research suggests that using a combination of multiple probiotic strains as well as probiotics that contain 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 microbes of the intestinal tract help extract nutrients and energy from food, which suggests a role for probiotics in the management of body weight. However, while some of the clinical trials that have evaluated the impact of probiotics on obesity-related endpoints have reported promising results, others have reported no effects.
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 the use of energy from the diet, but also energy expenditure and storage within the host [78]. Whether these effects translate to humans is unknown.
The results of clinical trials that have assessed the impact of probiotics on obesity-related endpoints have been inconsistent. One 12-week clinical trial, for example, randomized 210 healthy adults age 35 to 60 years who had large amounts of visceral fat to consume 200 g/day of fermented milk that contained 107, 106, or 0 (control) CFU of Lactobacillus gasseri SBT2055 (LG2055) per gram of milk [79]. 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 an RCT, 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 adults with obesity [80]. However, among female participants, those who received Lactobacillus had greater reductions in body weight after 12 weeks (loss of 1.8 kg) and 24 weeks (loss of 2.6 kg) than those who received placebo.
A 2017 systematic review of 14 clinical trials, including the two described above, in 1,067 individuals with overweight or obesity 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 [81]. Another recent systematic review and meta-analysis of 15 RCTs in 957 individuals with overweight or obesity 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 [82]. However, these effects were small and of questionable clinical significance.
In contrast, a more 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 [83]. 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 the loss of a mean of 0.54 kg in adults, the gain of a mean of 0.20 kg in children, and no significant weight loss or gain in infants [84].
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
Probiotics are unlikely to cause harm in healthy people, and side effects are usually minor. However, the use of probiotics has been linked to a few cases of bacteremia, fungemia, and infections that have resulted in severe illness; most of these cases involved individuals who were severely ill or immunocompromised.
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, common probiotics—such as Bifidobacterium and members of the Lactobacillaceae family—are unlikely to cause harm in healthy people [4]. Side effects of probiotics are usually minor and consist of self-limited gastrointestinal symptoms, such as gas.
However, some clinical trials of probiotics are not designed to adequately address questions about safety, leaving gaps in available safety evidence [85-87]. Moreover, some evidence indicates that probiotics may cause harm in certain populations, including people who are severely ill or immunocompromised. The 2023 FDA press release discussed above expressed concerns about the potential risks of administering probiotics to preterm infants [51].
The use of probiotics has been linked to bacteremia, fungemia (fungi in the blood), or infections that have resulted in severe illness in some cases, most of which involved individuals who were severely ill or immunocompromised [88,89]. 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 was confirmed to be the opportunistic pathogen. Because the species used as probiotics can also 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 that contain the yeast Saccharomyces cerevisiae. In many of these cases, the patients were in an intensive care unit (ICU), were receiving enteral or parenteral nutrition, had a central venous catheter, or had received broad-spectrum antimicrobial treatment [90]. When LGG was introduced into dairy products in Finland in 1990, monitoring of this country’s population through 2000 revealed no increase in the rates of bacteremia (bacteria in the blood) caused by Lactobacillus species [91]. However, a retrospective analysis of 22,174 ICU patients in a Boston hospital found that those who received LGG (typically through a feeding tube) had a markedly higher risk of developing Lactobacillus bacteremia compared to patients who did not receive the probiotic [92]. Of the 522 patients who received LGG, a genome-level analysis identified six cases where the ingested LGG was found in the blood, compared to only two cases among the 21,652 patients who did not receive the LGG.
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 [4]
Probiotic Selection and Use
There are currently no formal recommendations for or against the use of probiotics in healthy people. However, some expert bodies of health professionals provide guidance on the use of specific probiotic strains in people with certain health conditions. These groups also offer guidance for clinicians and consumers on choosing probiotic products.
Expert bodies of health professionals make no recommendations for or against the use of probiotics 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 and recommends that clinicians only advise their patients to use probiotic strains, doses, and durations that have been shown to be beneficial in human studies [4]. The WGO guidelines include a summary of the evidence on specific probiotic strains used in studies for specific gastrointestinal endpoints [4]. 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 CFU—ideally for each strain—through the expiration date or use-by date on the product label [93]. The association also suggests that consumers of these supplements avoid products that list the number of CFU at time of manufacture because this information does not account for declines in CFU over a product’s lifespan.