For Patients & Caregivers
What is it?
Probiotics are made of good bacteria and yeast. The good bacteria helps to fight off issues caused by bad bacteria, such as problems with digestion and bowel function. Taking probiotics helps balance out the bacteria in your stomach and can help you feel better.
Probiotics are found in many foods and drinks like yogurt, kefir, miso, and sauerkraut, and cottage cheese. You can also take probiotics as a dietary supplement in many forms that include:
What is it used for?
Probiotics are used to help:
- Prevent and treat diarrhea (loose or watery bowel movements).
- Treat inflammatory bowel disease (swelling in your digestive tract).
- Prevent gastroenteritis (stomach flu with symptoms including diarrhea, cramps, nausea, vomiting, and fever).
- Reduce symptoms of irritable bowel syndrome (IBS) (an intestinal disorder that causes pain in the belly, gas, diarrhea, and constipation).
- Reduce side effects caused by cancer treatment such as diarrhea and stomach pain.
- Treat urinary tract infections (UTIs)
Probiotics also have other uses that haven’t been studied by doctors to see if they work.
It’s generally safe to have foods and drinks with probiotics in them. However, talk with your healthcare providers before taking probiotics as supplements.
For more information, read the “What else do I need to know?” section below.
What else do I need to know?
- Talk to your healthcare provider before taking probiotics as a dietary supplement if you have a weakened immune system because of your cancer treatment. Some probiotics may cause harm.
- Talk to your healthcare provider before taking probiotics as a dietary supplement if you have a central venous catheter (CVC), such as an implanted port. Some probiotics may cause harm.
- Babies who are underweight, have umbilical catheters, or have low oxygen levels should not be given probiotics as they can cause harm.
For Healthcare Professionals
The term “Probiotic” (Greek for “prolife”) came into being in the 1960s to define substances produced by protozoa, which support the growth of other microorganisms (1). Following revisions over the years, probiotics are currently defined by the Food and Agriculture Organization of the World Health Organization as “live microorganisms, which when consumed in adequate amounts, confer a health effect on the host” (2). Most probiotics consist of lactic-acid producing, non-virulent bacteria, such as Lactobacillus, Streptococcus, Bifidobacterium, Propionibacterium and Enterococcus or non-pathogenic yeasts such as Saccharomyces boulardii. Probiotics have gained immense popularity over the last two decades for their perceived health benefits which include improved digestion, immune function and nutrient absorption but the most important being the reversal of dysbiosis (changes in the function or composition of gut microbes or “microbiota”) that is hypothesized to play a role in the development of several chronic and degenerative diseases (3). Although gut microbiota is known to develop at birth, nutrition, lifestyle, and changes in the host genome during later years can shift its makeup and activity, which in turn influences overall health and the risk of developing disease. Antibiotic use has also been associated with gut microbiota disruption in general population, increasing the risk of chronic disease (77); in patients undergoing allogeneic hematopoietic cell transplantation (4), with the greatest shifts occuring between stem cell infusion and reconstitution of healthy immune cells (75); as well as in allogeneic bone marrow transplantation patients (5). Furthermore, antibiotics were found to inhibit the benefits of immune checkpoint-inhibitors in patients with advanced cancer (78); and patients who were administered antibiotics before, and not during, immune checkpoint-inhibitor therapy had worse treatment response and overall survival (79). Research is underway to determine strategies for modulating the gut microbiome to improve immune response in cancer.
Probiotic supplementation is currently promoted for the prevention and treatment of inflammatory bowel disease, gastroenteritis, irritable bowel syndrome, allergies, dental cavities, and for the management of diarrhea induced by antibiotics, by the bacterium Clostridium difficile (C. difficile), and that associated with chemotherapy (64). However, authoritative guidelines for probiotic use have not yet been established nor is there a consensus about the minimum number of microorganisms needed to derive benefits.
Probiotics have been evaluated in randomized controlled trials and the strongest evidence of their effectiveness is for acute infectious diarrhea, the main cause of acute gastroenteritis (7). Probiotic supplementation also was shown useful in alleviating antibiotic-associated diarrhea (8). Although randomized trials did not find any benefit for managing C. difficile-associated diarrhea (9), a meta analysis suggests moderate quality evidence to support use of probiotics for preventing C. difficile infection (63). The role of probiotics in the treatment of inflammatory bowel disease (IBD) has been the focus of many studies and available data support their efficacy for pouchitis (inflammation of the ileal pouch in post-colectomy patients). Interestingly, even though a range of products were shown useful in treating and sustaining remissions of mild to moderately active ulcerative colitis, findings of Crohn’s disease are not promising (65). Based on the association of intestinal bacteria with symptoms of irritable bowel syndrome (IBS), probiotic supplementation has been explored in a few studies. Although current data are encouraging, well-designed trials to support use are lacking (11). In a study of patients with systemic sclerosis, probiotics did not improve gastrointestinal symptoms (67).
In addition, analyses of the National Health and Nutrition survey results revealed that consumption of yogurt or probiotics reduces the risk of proteinuric kidney disease (12), but definitive conclusions about the role of probiotics for the treatment of urinary tract infections (13) or bacterial vaginosis (60) are lacking. Probiotic use was also shown to increase resistance to risk factors associated with dental caries in a randomized trial (14), and to improve memory impairment in a murine model (15). The utility of probiotics in preventing allergies has been addressed as well, with studies showing a moderate benefit for eczema prevention but not for other allergic conditions (16). Probiotic supplementation was also shown useful for the reduction of glycemic and inflammatory markers in patients with non-alcoholic fatty liver disease (58). But evidence to support its role in managing cystic fibrosis is lacking (61). In other studies, supplementation did not have a preventive effect against influenza in women healthcare workers (82), nor against bacterial vaginosis in pregnant women (83).
As increasing evidence indicates that gut bacteria are important determinants of metabolic disorders, probiotics are being investigated as a possible therapeutic option. Thus far, beneficial effects have been reported against obesity and diabetes in mice and in humans (17). Meta analyses suggest that probiotic supplementation helps reduce periodontal parameters and halitosis associated with severe periodontitis (68), helps prevent oral candidiasis in the elderly (62), may lower fasting blood glucose level in adults (59) and may also improve lipid metabolism by lowering the levels of LDL and total cholesterol (18).
Another important application of probiotic therapy is in pediatrics for the treatment of gastrointestinal disorders and allergies. Meta analyses indicate that enteral supplementation of probiotics is effective in preventing severe necrotizing enterocolitis in preterm infants (19). And a significant reduction in acute diarrhea was reported in children, independent of the bacterial strains employed (7) (69). Studies also indicate efficacy of probiotics against antibiotic-associated diarrhea (20) and for lowering the incidence of eczema in late infancy (70). But available evidence does not support use for allergic diseases (21), and data are insufficient to assess effects in children with short bowel syndrome, a malabsorption disorder (22).
Preliminary studies also suggest that probiotics may have anti-carcinogenic potential. Preclinical data show that oral administration of Lactobacillus casei BL23 has a protective effect against dimethyl hydrazine-induced colorectal cancer (23), and a probiotic mixture attenuated the growth of hepatocellular carcinoma (24). A study done in a murine model of melanoma suggests that manipulating the microbiota may modulate cancer immunotherapy, by enhancing antitumor immunity in vivo through administering a Bifidobacterium strain (71). Findings also suggest that gut microbiome may modulate responses to anti PD-1 immunotherapy in melanoma patients (80). Data from a large epidemiological study suggest an association between consumption of non-pasteurized dairy products and lower incidence of colorectal cancer (25). Probiotics may also aid in controlling symptoms associated with cancer treatments. Results from a systematic review showed a reduction in the severity and frequency of treatment-associated diarrhea, and the need for anti-diarrheal medication in cancer patients following probiotic supplementation (26). In other studies, perioperative probiotic treatment reduced surgical site infections in patients undergoing colorectal cancer surgery (27) and improved bowel function (28). But supplementation was ineffective for preventing radiation-induced mucositis in patients with head and neck cancer (72). More studies are underway (29).
In addition to probiotics, other strategies used to modulate gut microbiota that have recently gained attention include “prebiotics” and “fecal microbiota transplantation” (FMT). Prebiotics, also known as functional foods, are non-digestible food ingredients that benefit the host by selectively promoting growth or activity of helpful gut bacteria. Currently used prebiotics include the fructans inulin and fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), and lactulose. A few studies have evaluated the utility of prebiotics for IBS but data are conflicting (11). Because probiotics are short-lived, prebiotics are being co-administered to maintain their levels in the gut. This combination of pro- and prebiotics is called “synbiotic therapy” that has been shown useful in controlling symptoms associated with IBS (30); and may also benefit gut functioning in healthy community-dwelling elders (84). FMT involves administration of fecal matter from a healthy donor into a recipient by enema, colonoscopy or through the upper gastrointestinal tract in the form of oral capsules, via nasogastric, nasoduodenal or nasoenteric tube, or by endoscopy, to restore normal gut flora. Some studies indicate that FMT might benefit IBS patients although the quality of evidence is low (31). In oncology settings, FMT has been reported effective for treating immune checkpoint inhibitor (ICI)-associated colitis (81); and autologous fecal microbiota transplantation (auto-FMT), for reestablishing intestinal microbiota composition in patients with gut microbiota depletion due to antibiotic treatment during allogeneic hematopoietic stem cell transplantation (76).
Although an increasing number of studies suggest that probiotics improve health by inducing favorable changes in the intestinal bacteria, the overall evidence to support their use is limited due to small sample size, poor methodology, variation in the species and strains of bacteria, and in the dosage and duration of administration. Variation in the response to probiotics is also an important factor to consider because genes that respond to probiotic intake were shown to be strain-specific (32) and to cluster according to the individual and not by intervention (32) (33). Furthermore, gut colonization is not always achieved despite supplementation with probiotics (73). In another study that examined post-antibiotic recovery in humans, administration of probiotics was associated with a delay in gut-microbiome reconstitution (74). Well-designed studies and specific recommendations are needed to establish probiotic use for different age groups and disorders.
Probiotics are generally considered safe, but their long-term safety has not been determined. Bacteremia, fungemia, and endocarditis have been reported following use in newborns and in immunocompromised individuals.
Mechanism of Action
Proposed mechanisms by which probiotics influence colonization in the gut include production of inhibitory compounds to suppress the growth of pathogenic microorganisms, and production of substrates to promote the growth of beneficial bacteria. Probiotics can also indirectly influence shifts in microbiota by interacting with the mucosal system, which affects systemic immunity; and by reducing pro-inflammatory markers implicated in many disorders (34) (35).
Studies using murine models indicate that administration of S. boulardii to type-2 diabetic and obese mice resulted in reduced inflammation, body weight, fat mass, and hepatic steatosis, along with decreased bacterial population that has been previously associated with obesity and type-2 diabetes (36). Probiotic treatment also affected a reduction in food intake and an improvement in glucose tolerance via release of the hormone glucagon-like protein-1 (GLP-1), a physiological regulator of appetite and food intake (37).
Immunomodulation is one of the ways in which probiotics are thought to influence host health. A subspecies of Bifidobacterium longum prevented Salmonella-associated infection in mice by inducing T-regulatory cells and by attenuating the activation of nuclear factor-kappa B, which plays a role in the expression of pro-inflammatory genes (38). Induction of T-regulatory cells was also shown in humans along with a reduction in pro-inflammatory biomarkers (39). In addition probiotic administration was shown to reduce pain perception, and to induce changes in the colonic expression of genes that mediate pain and inflammation (40). And a probiotic mixture reduced the growth of hepatocellular carcinoma by shifting the gut microbes toward beneficial bacteria, which produce anti-inflammatory metabolites (24). Protective effects of probiotics were also reported in a murine model of mammary carcinogenesis. Oral administration of a supplement containing Lactobacillus reuteri resulted in inhibition of mammary tumor formation by triggering CD4+/CD25+ lymphocytes, which play a critical role in controlling immune responses (41). Because intestinal bacteria have been shown to influence carcinogenesis and response to anticancer therapy, manipulating them selectively may be a potential strategy to enhance the efficacy of anticancer treatments (66).
- Patients who are immunocompromised, or have a central venous catheter or critically ill should not take probiotics containing S. boulardii (42).
- Probiotics should not be given to newborns with very low birth weight, clinical instability, umbilical catheters, and to those with congenital abnormalities or stage III asphyxia (43).
Pediatric Case Reports:
- Bacteremia associated with Escherichia coli and Bifidobacterium species: In pre-term infants (44) (45) (46) as well as a newborn (47) following probiotic therapy.
- Probiotic-associated L. rhamnosus pneumonia: In a 11-month-old baby, secondary to a respiratory viral infection. She recovered after antibiotic therapy (49).
- D-lactic acid encephalopathy, involving intermittent ataxia: In a 5-year-old girl following use of probiotics to control diarrhea. She was treated with oral antibiotics (50).
- Bacteremia associated with Lactobacillus: In a 17-year-old boy with ulcerative colitis. His symptoms, which included fever, flushing and chills resolved following treatment with antibiotics (48).
Adult Case Reports:
- Fungemia involving Saccharomyces cerevisiae: In a patient with Clostridium difficile-associated diarrhea who was treated orally with the probiotic yeast Saccharomyces boulardii (51).
- Sepsis associated with Saccharomyces cervesiae: In a 34-year-old woman with extensive burns, and administered Saccharomyces boulardii to improve the digestive tolerance to enteral feeding (52).
- Fungemia: In a 79-year-old woman following treatment with Sacchaflor (a probiotic consisting of S. boulardii) for Clostridium difficile-associated diarrhea. Her symptoms improved after discontinuing use of Sacchaflor (53).
- Lactobacillus empyema: In a 54-year-old HIV-infected lung transplant patient, after taking a probiotic containing Lactobacillus rhamnosus GG. His symptoms resolved with antibiotic treatment (6).
- Lactobacillus acidophilus bacteremia: In a patient with AIDS and Hodgkin’s disease following probiotic therapy containing L. acidophilus (54).
- Sepsis due to preoperative administration of a probiotic containing Lactobacillus rhamnosus: In a 24-year-old woman following an aortic valve replacement. She was treated with antibiotics (55).
- Bloodstream infection: In a critically ill 64-year-old patient with acute pancreatitis, following administration of a symbiotic formula containing Pediococcus pentosaceus. He was treated with antibiotics (56).
- Accidental septicemia: In a 25-year-old man, following intravenous administration of a probiotic containing Bacillus clausii. He recovered after a 5-month course of combined antibiotics (85).
- Hepatic drug-metabolizing enzymes: In mice, administration of VSL3, a probiotic mixture of 8 bacterial strains, was shown to modify the expression of Cyp4v3, alcohol dehydrogenase 1, carboxyesterase 2a, and multiple phase II glutathione-S-transferases (57). Human data are lacking.