Antibiotics are among the most commonly prescribed medications in both outpatient and hospital settings. Global efforts at curbing antibiotic-resistant strains have prompted clinicians to pursue better stewardship, whereby they limit their prescribing of such medications to those who truly need them.
Yet there’s another possible means of addressing antibiotic resistance — using dietary interventions to reduce the gastrointestinal (GI) complaints that so often accompany the use of antibiotics: vomiting, nausea, diarrhea, bloating/indigestion, abdominal pain, and loss of appetite. Far from being a mere nuisance, these complications can have major ramifications.
“Often [these side effects] will result in people stopping an antibiotic they need or taking a second- or third-generation one, which potentially causes even more problems with resistance,” explained Daniel J. Merenstein, MD, a professor of family medicine at Georgetown University, who has conducted multiple trials on antibiotic stewardship and probiotics.
And it’s not just clinicians who would like to find a way around these common complaints. On lifestyle blogs such as Livestrong and Goop, medical news websites, and via academic institutions, patients can learn how the right probiotic supplement or certain fermented or high-fiber foods, for example, might spare them the upset stomach that often accompanies a course of antibiotics.
Yet according to experts in the field, there are notable questions to be answered about whether there’s evidence to support this approach.
The Cost of GI Discomfort
Pinpointing the exact manner by which antibiotics upend GI tracts is a complex task, according to Gail Cresci, PhD, RD, a microbiome researcher in the Department of Pediatric Gastroenterology, Hepatology, and Nutrition and director of nutrition research at the Cleveland Clinic.
“A lot of different mechanisms can go awry,” Cresci told Medscape. “But normally, the good microbes are there to help keep the balance, so when that balance is gone, the pathogens can take over and lead to this disruption.”
According to Lynne V. McFarland, PhD, a recently retired infectious disease epidemiologist who now serves as a private consultant, such complications can have substantial ramifications for patients and healthcare systems.
“If you’re an inpatient and develop antibiotic-associated diarrhea, it usually increases the length of stay from 8 to 20 days. It also increases the cost of care. And small children who have this can get severely dehydrated, which can become life threatening.”
Proponents of Probiotics
Several of the researchers who were interviewed believe there’s convincing evidence supporting probiotics for the treatment of common antibiotic-related GI complaints. In many instances, they were involved in the studies themselves.
During McFarland’s 4-decade career in probiotics research, she has participated in early animal studies with strains such as Saccharomyces boulardii and was involved in meta-analyses of their role in Clostridium difficile infection and associated diarrhea and even as a potential GI intervention for COVID-19 patients.
In mouse model studies from 2013 and 2018, Cresci and colleagues showed that the probiotic strains Lactobacillus GG and Faecalibacterium prausnitzii reduced the structural gut changes that lead to antibiotic-associated diarrhea and minimized the risk of C difficile infection.
In a 2021 randomized controlled trial led by Merenstein, healthy participants were given a trial of amoxicillin/clavulanate (days 1–7) in conjunction with either yogurt containing the probiotic Bifidobacterium animalis subsp lactis BB-12 or control yogurt (days 1–14). After assessing feces samples over a 30-day period, they found that those who received the probiotic yogurt had a significantly smaller decrease in short-chain fatty acid levels and a more stable taxonomic microbiota profile than control persons.
Merenstein said that on the basis of results such as these and others, he’s comfortable being relatively definitive about the value of probiotics.
“I believe it’s close to standard of care that if you’re prescribing antibiotics, especially for more than 7 days, you really need to put people on probiotics that have been studied, simply because the evidence is robust enough now,” he said.
Even for Proponents, There Are Caveats
However, all the researchers recommending the use of probiotics did so with caveats. First and foremost, they advise clinicians that the term “probiotics” is an imprecise catchall and is essentially meaningless.
“A lot of products label themselves as probiotic. It’s a great marketing scheme, but many of the products out there aren’t really probiotics; they’re not proven with randomized control trials and don’t have the scientific background,” said McFarland. “We’ve found that the efficacy is extremely strain specific and disease specific. A strain may work for one disease and not work for another.”
In 2018, McFarland co-authored an evidence-based practical guide to help clinicians and patients identify the specific strain that works in certain indications. Cresci recommends that clinicians consult websites such as Probiotics.org or the National Institutes of Health’s database to find the strains that have been proven to work in well-designed clinical trials.
There was also agreement that, to date, the most robust data support probiotics for the treatment of antibiotic-associated diarrhea.
Although the optimal timing of probiotics is a subject of debate, most proponents agree that the general rule is “the sooner the better.”
McFarland recommends incorporating probiotics within 24 hours of starting an antibiotic “because the damage done to your GI tract microbiome is pretty quick, and the probiotics work best if they’re established before major disruption occurs.” She added that patients should continue taking probiotics for 2 to 8 weeks after stopping antibiotics.
“It takes a long time for your normal flora to get restored,” she said. “It’s best to cover your bases.”
For Others, the Evidence Is Not Definitive
Opinions on the value of probiotics to combat antibiotic-related GI side effects are divergent, though.
“I would not recommend the routine use of probiotics, and certainly not in the prevention of C difficile or antibiotic-related diarrhea,” said David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, who is also a Medscape contributor. “I think the evidence does not support that, and I stand strongly on that recommendation.”
Johnson cited the 2020 guidelines from the American Gastroenterological Association (AGA), which offer only a conditional recommendation for the use of specific probiotics and only in preventing antibiotic-associated C difficile infection.
Geoffrey A. Preidis, MD, PhD, an assistant professor of pediatrics in the Section of Gastroenterology, Hepatology and Nutrition at Baylor College of Medicine, served as a co-author of the AGA’s guidelines. He noted that after reviewing 39 published trials of approximately 10,000 patients given probiotics while receiving antibiotics, the authors “did find some evidence that specific probiotics might decrease the risk of C difficile diarrhea, but the quality of that evidence was low.”
Preidis attributed this to the lack of well-designed multicenter trials that can isolate the effects of certain strains and determine their benefit in this application.
“The majority of published trials have not reported safety data as rigorously as these data are reported in pharmaceutical trials, so the risk of side effects could be higher than we think,” said Preidis. “As living microbes, probiotics can move from the intestines into the bloodstream, causing sepsis. Contamination in the manufacturing process has been reported. There might be other long-term effects that we are not yet aware of.”
When asked to characterize the available data on probiotics, Johnson replied, “I’d generally label it, ‘caveat emptor.’ “
McFarland agreed that the field would benefit from better-designed studies and called out meta-analyses that pool outcomes with various strains for particular criticism.
“When researchers do that, it’s no longer valid and shouldn’t have been published, in my opinion,” she told Medscape.
“Antibiotic Diets” as a Possible Approach
A compromise between the two sides may be the so-called antibiotic diet. The theory behind such diets is that foods and beverages with biome-boosting properties may be a risk-free intervention that patients can adopt to alleviate antibiotic-related side effects.
“You want your diet to include more soluble fibers to help support the good bacteria, particularly when you’re taking antibiotics,” said Cresci. “You can get this through eating fresh fruits and vegetables, whole grains, and foods that have more prebiotic, like potatoes. You can also eat fermented food, such as kefir, kombucha, kimchi, and yogurt, so you’re adding more beneficial bacteria into your intestinal tract.”
There is ample published evidence that such foods can boost microbiome diversity and decrease inflammation, including a July 2021 study in Cell. However, the protection this may confer while taking antibiotics isn’t known. Establishing a clear role for the efficacy of such interventions is made additionally difficult by the well-established limitations of conducting dietary clinical trials.
Merenstein said that there is no compelling evidence that antibiotic-related complications can be offset by changing what goes onto our dinner plates. He joked, “We can’t say, ‘Here’s amoxicillin for your ear infection, now make sure you increase your fermented food, fiber, and water.’ “
Johnson said he’s intrigued by studies of prebiotics — fibers that boost beneficial bacteria in the GI system.
“I would love to have more findings about prebiotic identification; that is, things we could do in a healthy way to keep the gut balanced while it’s subject to a change with antibiotics,” he said. “We’re just not there yet.”
Johnson added that he generally recommends that patients taking antibiotics eat “a bland diet, avoiding things that may have been provocative in the past.”
If patients are already enjoying foods with microbiome-boosting reputations, Johnson sees “very little downside to continuing that [while on antibiotics].” However, he noted that the period in which you’re taking antibiotics isn’t ideal for trying new foods, given the lack of experience with how the gut bacteria will react.
There are data about foods to avoid while taking antibiotics, which generally fall in line with common dietary knowledge. Many patients may know not to drink grapefruit juice with certain medications, but it’s worth a reminder. Certain antibiotics may also require delaying or avoiding dairy products, although this does not apply to yogurt.
A fiber-deficient diet can aggravate microbiota collapse following antibiotics. In a 2020 study, researchers showed that people on a high-fat diet who were using antibiotics were 8.6 times more likely to have preinflammatory bowel disease than those eating low-fat foods and who had no recent history of antibiotic use. Mouse model data from the same study indicated that poor diet and antibiotics may have worked in conjunction to reduce oxygen in the gut.
McFarland notes that building a healthy microbiome is a lifelong pursuit and that several factors (eg, environmental, genetic) are out of individuals’ hands. The general public might want a quick fix — ironically, one of the main drivers behind their requesting and receiving antibiotics when they’re not indicated — but it’s likely not available to them.
“You can’t eat one salad and suddenly have a healthy gut, unfortunately.”
John Watson is a freelance writer in Philadelphia, Pennsylvania.