May 2020 Issue
Probiotics in Diarrhea Treatment
By Densie Webb, PhD, RD
Vol. 22, No. 5, P. 24
Research suggests they may offer great potential, but proof of benefits remains mixed.
Probiotics are extremely popular, and that trend shows no sign of decreasing. In fact, the US probiotic market, which includes probiotic foods, beverages, and supplements, reached $6 billion in sales in 2016 and is estimated to almost double by 2025.1
Probiotics are defined as live microorganisms that are intended to have health benefits when consumed or applied to the body. They’re thought to improve gastrointestinal (GI) health and help balance the gut microbiome. This definition, established in the 1970s, still is maintained today.2 Probiotics are available in seemingly infinite combinations of bacterial strains and doses in supplements, foods, and drinks. The most common probiotics belong to the Lactobacillus and Bifidobacterium families, but there are many other families, and the effects of specific strains within those families vary. For example, one strain of Lactobacillus may be beneficial for a specific condition and even a specific individual, but that doesn’t mean another strain will be as effective for that condition or for another individual.
One of the most researched topics on probiotics is whether they can help prevent or alleviate diarrhea. Diarrhea has a variety of causes and is usually self-limiting, resolving on its own within four days.3 But it’s unpleasant, and anything that can shorten its duration usually is welcome by patients. While probiotics and their effect on diarrhea have been studied extensively—and several studies have found them to shorten its duration—research methods and results vary widely and questions remain regarding their efficacy and safety.4
Diarrhea resulting from taking a course of antibiotics is common, both in children and adults. An estimated 5% to 39% of patients will be affected from the beginning of treatment and for as long as two months after treatment has ended.5 Diarrhea probably is the most studied area with regard to probiotic use as a treatment and preventive measure. Overgrowth of Clostridium difficile (C diff) in the intestine is the most common result of antibiotic treatment and the most common cause of antibiotic-associated diarrhea. Antibiotics linked with the highest risk of C diff infections include fluoroquinolones, cephalosporins, and clindamycin.6 Several large reviews and analyses have been conducted to evaluate probiotics’ effects on reducing the risk of antibiotic-associated diarrhea, but none have provided clear recommendations.
A 2016 meta-analysis of 30 randomized controlled trials of adults aged 18 or older found a positive association between probiotic intake and reduced risk of antibiotic-associated diarrhea in those younger than 65. No positive association was found in patients aged 65 or older.7 That could be important to mention during counseling sessions, as antibiotic-associated diarrhea and C diff infection are more common in older adults. Lactobacillus rhamnosus GG and Saccharomyces boulardii were the two strains that demonstrated a positive effect.
A 2017 review of 17 studies with a total of 3,631 outpatients found that taking probiotics along with antibiotics was associated with an approximately 50% decrease in antibiotic-associated diarrhea. The most effective probiotic strains again were L rhamnosus GG and S boulardii.8
A review of 23 studies examined the ability of probiotics to prevent antibiotic-associated diarrhea in children. The reviewers found moderate evidence among the 3,938 participants that probiotics provided a protective effect.9 Some of the studies used single strains, while others used a variety of combinations of different strains, making it difficult to identify the most efficacious probiotic strains. However, the authors suggested that L rhamnosus or S boulardii might be the most effective.
Another systematic review and meta-analysis examined 31 studies totaling 8,673 participants who took probiotics and experienced the resulting antibiotic-associated diarrhea caused by C diff.10 The study concluded that, when participants took probiotics with antibiotics, the risk of developing antibiotic-associated diarrhea was reduced by 60% on average. Several probiotic strains were used, but Lactobacillus strains were frequently the probiotics used in the included studies. A 2010 meta-analysis of 10 studies and 1,862 patients had similar findings. Supplementation of L rhamnosus GG for five to 14 days in that analysis reduced the risk of antibiotic-associated diarrhea by 65%.11
Research also has been done on the efficacy of probiotics in reducing diarrhea in children with gastroenteritis. Referred to as the “stomach flu,” gastroenteritis can be the result of viruses, bacteria, or parasites causing inflammation in the stomach and small intestine. When caused by contaminated foods or beverages, it’s commonly called “food poisoning.”
Probiotics are thought to aid in lessening diarrhea caused by gastroenteritis. In a recent systematic review and meta-analysis of children with acute gastroenteritis, researchers gave participants either a placebo or Lactobacillus reuteri at varying doses. Those given the probiotic experienced a reduction in the duration of diarrhea by about one day (21 hours).12 A meta-analysis of five randomized, controlled trials evaluating two strains of L reuteri found that both strains reduced the duration of diarrhea.13 However, in other studies, researchers found no beneficial effects of L rhamnosus GG and Lactobacillus helveticus in the treatment and prevention of acute gastroenteritis in children.14,15
Diarrhea is a common side effect of chemotherapy or radiotherapy in cancer treatment, affecting as much as 80% of patients.16 It has been suggested that probiotics might help prevent or treat this type of diarrhea. Research on various strains and doses of probiotics has suggested that the coadministration of probiotics with radiotherapy can help prevent diarrhea.17 However, a 2018 review of 12 studies with 1,554 participants couldn’t find conclusive evidence of a beneficial effect.16
While one review of 11 studies concluded that probiotics may help prevent chemoradiotherapy-induced Grade 2 or greater diarrhea (an increase of four to six stools per day),18 a recent meta-analysis of seven randomized controlled trials found that, compared with placebo, prophylactic probiotics didn’t prevent or reduce the incidence of chemotherapy-induced Grade 3 or greater diarrhea (increase of seven or more stools per day).19
Contradictory findings also resulted from a 2019 meta-analysis of 13 randomized controlled trials, which found that a variety of probiotics significantly improved Grade 3 and 4 diarrhea in patients receiving chemotherapy, but not in those experiencing Grade 1 or 2 diarrhea.20
Irritable Bowel Syndrome
Research also has been conducted on probiotics and irritable bowel syndrome (IBS), a group of symptoms that occur together, including abdominal pain, diarrhea, constipation, or both. IBS, which affects an estimated 11.8% of Americans, is more common in women than in men and in individuals aged 30 to 49.21,22
The evidence for a beneficial effect of probiotics on IBS is limited. Randomized controlled trials to test the efficacy of probiotics on IBS typically have been small. However, two recently published studies found probiotics to be beneficial. The first study included 80 patients with IBS who took part in a multicenter, double-blinded, parallel, placebo-controlled, randomized trial. Subjects were given either a two-strain mixture of Lactobacillus acidophilus or placebo for eight weeks. Taking probiotics significantly decreased gas and the severity but not the frequency of abdominal pain.23
The second study was a systematic review and meta-analysis of 28 studies with a total of 3,606 participants. The study found that certain combinations of probiotics or specific species and strains appeared to have beneficial effects on IBS symptoms and abdominal pain, but researchers couldn’t draw definitive conclusions about their efficacy.24
A variety of single probiotic strains, mixtures of strains, and different dosages were administered in the studies included. However, overall, probiotics appeared to have a beneficial effect on IBS symptoms.
Probiotics generally are considered safe. And clients and patients who assume they’re safe are, for the most part, correct. However, Kate Scarlata, MPH, RDN, LDN, owner and operator of For A Digestive Peace of Mind, LLC, in Medway, Massachusetts, says, “As a general rule, probiotics appear to be safe in healthy people, but it’s important to note that probiotics are generally unregulated, just like vitamins and supplements.”
Kristi King, MPH, RDN, LD, CNSC, a senior pediatric dietitian at Texas Children’s Hospital in Houston, a clinical instructor at Baylor College of Medicine, and a spokesperson for the Academy of Nutrition and Dietetics, agrees: “Research indicates probiotics are safe, but those who are elderly and anyone who’s immunocompromised should be aware of potential side effects.”
Side effects may include a change in bowel habits, bloating, and a change in the gut microbiome that may not be for the better. Furthermore, King says there are currently no case reports or guidelines regarding length of use. “Each study that has been done typically has its own protocol, so no standards have been set,” she says.
One small study has suggested that taking probiotics following antibiotics may delay the ability of the gut microbiome to “bounce back” and return to normal. The researchers gave 21 subjects an oral broad-spectrum antibiotic for seven days. Then, they gave some subjects nothing, administered to others a fecal transplant (introducing a new gut microbiota to their GI systems), or provided a probiotic supplement that contained 11 different strains twice daily for four weeks. Participants given the probiotic supplements experienced a significant delay in their microbiome recovery to a normal bacterial balance compared with subjects given nothing. In contrast, subjects administered a fecal transplant experienced a rapid and near-complete recovery within days of administration.25
Because of wide variation in study design (number, age, and gender of subjects), as well as probiotic strains, dosages, timing of dosing, and trial length, most experts say it’s hard to come to a definite conclusion on the efficacy of specific probiotics for the prevention and treatment of diarrhea in general and for specific conditions.
Stephen Freedman, MD, a researcher at the University of Alberta, in Edmonton, Alberta, Canada, and principal investigator on several probiotic multicenter clinical trials, summarizes the current state of knowledge: “The evidence supporting the use of probiotics is weak at best and is generally based on small, low-quality clinical trials, with most larger, high-quality, multicenter clinical trials reporting that probiotic administration is not beneficial. As with any therapeutic intervention, one must consider the potential benefits, complications, and cost.”
If dietitians are still unsure about how to counsel patients, Scarlata suggests the Clinical Guide of Probiotic Products as an evidence-based resource to select a probiotic for use. RDs can download the guide, which is an app, at https://bit.ly/339DBqb.
Sherry Coleman Collins, MS, RDN, LD, owner of Southern Fried Nutrition, based in Marietta, Georgia, recommends patients take probiotics for about two to three weeks to see whether they make a difference.
Each individual has his or her own unique microbiota, and the impact of a given antibiotic on the composition and stability of different microbial systems can be different. A specific probiotic strain or combination of strains may not have the same efficacy for every person.26 Large, well-designed, and rigorous trials using specific strains and standardized doses of probiotics are needed before probiotics can be recommended with any confidence for their ability to alleviate diarrhea in any one individual for any one condition.
However, King has a different take-home message: “I’d encourage people to save money and get a majority of their probiotics from food, such as plain, no-sugar-added yogurt or kefir.”
— Densie Webb, PhD, RD, is a freelance writer, editor, and industry consultant based in Austin, Texas.
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