Probiotics: Enthusiasm not supported by evidence
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Probiotics are used by millions of people around the world. Sales in the United States alone are expected to grow to more than $6 billion in 2020. Despite their wide reach in the consumer market, scientific data on probiotics’ real benefit have been lacking.
As the understanding of the gut microbiome has grown, patients and the physicians who treat them have sought out ways to target that community of microbes as a means for treating any number of conditions, particularly gastrointestinal disorders.
“Heath care professionals and patients alike were incredibly enthusiastic about the promise of probiotics,” William Chey, MD, from the University of Michigan School of Medicine, told Healio Gastroenterology. “Conceptually, there are many reasons why you can build an argument about why probiotics are beneficial. Unfortunately, all of those concepts that we subscribe to, including myself, are oversimplifications of what is really happening in the body.”
Earlier this year, the American Gastroenterological Association published new recommendations on the use of probiotics in GI conditions. Looking at eight areas of concern, the authors could only make recommendations in three very specific conditions; for the prevention of Clostridioides difficile infection in adults and children who take antibiotics, in patients with pouchitis, and in preterm, low-birthweight infants for necrotizing enterocolitis.
Where do probiotics stand following these new recommendations, and how can physicians in GI, primary care and pediatrics, counsel patients who are already convinced that probiotics are beneficial for any number of ailments?
“This is an incredibly popular concept that has really taken off, but marketing has outstripped the evidence,” Chey said. “If you would survey the general population, the vast majority would think there are good bacteria and bad bacteria, and taking probiotics is good for certain things.
Source: Grace Su, MD.
“The vast majority of the use of probiotics can be categorized as nonevidence-based indications. The good news is that they’re safe, and they’re not going to hurt you. The bad news is that with few exceptions, they’re probably a waste of money.”
From Concept to Consumer
One of the challenges of advising patients around probiotics is that they sound so fantastic as an idea, Grace Su, MD, from the University of Michigan said.
“We’ve only recognized in the last 15 years that our gut has a whole colony, whole city, whole world of microbes in there that constitute the microbiome,” she said. “We all have this idea that we know what the microbiome is controlling in our health and GI health in particular.”
The thought process becomes pretty simple, she said. The “good bacteria” will take over from the “bad bacteria” that is causing whatever malady a patient is dealing with.
“The problem is, we’re not there yet,” Su said. “We have no idea which bacteria are good or bad yet. That concept is a little broad.”
People may want a magic pill to cure chronic diseases, but Su said thinking this way about probiotics could be problematic. While rigorous science is needed, important information is funneled from probiotic companies directly to consumers. As one of the authors of the AGA guidelines, Su said they hope to address this data gap by encouraging more hard science in probiotics.
“[Consumers] get told ‘this is probiotic, it’s good for you,’” she said. “Yes, in certain conditions the right probiotic is good for you. The problem is there is a lot of research that needs to be done. What we hoped to do is stimulate people to do that research. We know the promise is there, the idea is good, and we know it could help. The data just aren’t there.”
David Suskind, MD, from the division of gastroenterology at Seattle Children’s Hospital, said misconceptions around probiotics create a lot of noise that can take the focus off of treatments that are actually effective.
“If there is a therapy that is not effective, or a therapy that diverts attention from proper therapy, whatever the condition is, it’s problematic,” he said. “Education is going to be very important. Many times in medicine we’re looking for this silver bullet. Probiotics are definitely not that.”
AGA Recommendations
In the “AGA Clinical Practice Guidelines on Probiotics and Gastrointestinal Disorders,” there is only enough evidence to make just three conditional recommendations for using probiotics.
The first is in adults and children on antibiotic treatment for the prevention of C. difficile infection. In this patient group, the guidelines suggest the use of S. boulardii, the two-strain combination of L. acidophilus CL1285 and L. casei LBC80R, the three-strain combination of L. acidophilus, L. delbrueckii subsp bulgaricus, and B. bidum; or the four-strain combination of L. acidophilus, L. delbrueckii subsp bulgaricus, B. bidum, and S. salivarius subsp thermophilus. However, the authors noted that patients could reasonably opt for no probiotics if they had concerns for potential harm or the associated cost, or they placed a low value on the risk for C. difficile, particularly in an outpatient setting.
The second recommendation was for adults and children with pouchitis. In this patient population, the AGA suggested the eight-strain combination of L. paracasei subsp paracasei, L. plantarum, L. acidophilus, L. delbrueckii subsp bulgaricus, B. longum subsp longum, B. breve, B. longum subsp infantis, and S. salivarius subsp thermophilus.
Finally, the AGA recommended probiotics in preterm (< 37 weeks gestational age), low-birth weight infants for the prevention of necrotizing enterocolitis. For these patients, they suggested L. reuteri, L. rhamnosus or a combination of Lactobacillus spp and Bidobacterium spp.
In four other areas of focus, the authors could make no recommendations, including in patients with C. difficile, in Crohn’s disease, in ulcerative colitis and in irritable bowel syndrome.
“My area of focus is IBD, and in this chronic condition, people are looking for a simple treatment without side effects,” Suskind said. “They go to probiotics, supplements and things of that nature. The data are not supportive of the use of probiotics in most cases of IBD, and therefore we shouldn’t be using them in that condition.”
In 2018, Chey was part of a team at the American College of Gastroenterology that compiled a monograph on the management of IBS. In the document, they provided the most up-to-date information on common therapies in the condition. That included treatments that modified the gut microbiome like prebiotics, synbiotics, antibiotics and, of course, probiotics. Although they suggested that probiotics could improve global symptoms in IBS, the recommendation was weak, and the quality of evidence was low.
“The evidence does not support specific strains or products,” he said. “Yes, if you put all the studies into the meta-analysis blender, it looks like there is some benefit, but we did not have the confidence to recommend specific products, which shows you that the data are not very good.”
The AGA made one more recommendation, but it was against the use of probiotics in children with acute infectious gastroenteritis.
Although previous studies have shown promise in this area, Su said their findings have not been substantiated in North American patient populations.
“Previous studies were from outside the United States, and there are different bugs that cause gastroenteritis in other countries,” she said. “Studies in the U.S. have been negative.”
Proper Research, Advice for Patients
When a patient or parent asks for specific advice about potential treatments, Suskind said it is important to give them the necessary information. In probiotics, that means acknowledging the lack of evidence to support their use in gastrointestinal conditions.
“If families come in and ask, the important thing to do is to educate,” he said.
GI conditions and their interaction with the gut microbiome come with too many variables to be solved by one-size-fits-all probiotic treatment, according to Chey, who said relying on these treatments to provide a reproducible or consistent result is “illogical.”
“There are lots of reasons people develop specific symptoms, and manipulating the diet or putting in a probiotic is likely to impact the pathophysiology in only a subset of patients,” he said. “Down the road, until were able to approach this in more of a precision medicine approach, our strategies are not going to work that well.”
“There’s tremendous amount of hope there. It’s possible we will be able to leverage information gained from the microbiome in patients, or the metabolome, to choose the right treatment for the right treatment. That could be true for any microbiome-based therapy,” Chey said.
For probiotics to move forward as a treatment for GI conditions, they are going to need more rigorous research, Su said.
“When research is done, it needs to be done in a clean way,” she said. “[Investigators] need to report exactly what strains they’ve given people and monitor them very well, including if there is any toxicity. It needs to be very proactive in terms of stringency, which means reporting strains, reporting specific doses, any possible negative consequences.”
Despite the current lack of evidence, Su said there is still hope for the future of probiotics.
“I don’t want to discourage people from thinking this will work,” she said. “These are the data we have, so don’t waste your money, but let’s go do more studies and have probiotics live up to their promise.”
- References:
- Ford AC, et al. Am J Gastroenterol. 2018;doi:10.1038/s41395-018-0084.
- Preidis GA, et al. Gastroenterology. 2020;doi:10.1053/j.gastro.2020.05.060.
- Su GL, et al. Gastroenterology. 2020;doi:10.1053/j.gastro.2020.05.059.
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