Probiotics are wildly popular. After all, the microbial cocktails are available over the counter and have been shown to be helpful in the treatment of gastrointestinal illnesses for some people.
But some scientists worry probiotics aren’t as innocuous as they seem — and might be affecting the way other medicines work in the body.
The latest cautionary note comes in the form of a preliminary study released Tuesday, in which researchers found that melanoma patients were 70 percent less likely to respond to cancer immunotherapy if they were also taking probiotic supplements. The study group was small — just 46 patients — but the findings support broader suggestions that probiotics might actually upset the balance of so-called “good” bacteria in the gut and interfere with the immune response.
The research was conducted by MD Anderson Cancer Center in Houston and the Parker Institute for Cancer Immunotherapy in San Francisco.
“We wanted to bring this to the forefront of people’s minds: That probiotics sold over the counter aren’t necessary,” said Dr. Jennifer Wargo, lead author of the study and an associate professor of surgical oncology at MD Anderson. “They may not help you, and might even harm you.”
The microbiome — or rather, the trillions of distinct bacteria that flourish in every single gut — is now believed to play a substantial role in regulating a person’s overall health. The demand for probiotic supplements is expanding rapidly, as consumers attempt to self-correct perceived imbalances in their guts; the global market, in 2013, was valued at $36 billion.
But because probiotics — like vitamins and other such supplements — are only loosely regulated by the Food and Drug Administration, consumers are free to sprinkle these prepackaged bacterial spores in with their standard therapeutic regimens. And that could have serious implications for their medical outcomes.
“I strongly, strongly question why the general public takes probiotics when medical evidence to this routine is not really available,” said Eran Elinav, an immunology researcher at the Weizmann Institute of Science in Israel.
Probiotic mixes vary dramatically from pill to pill. Companies aren’t even required to maintain the same combination of bacterial strains from one batch to the next, meaning what people put in their bodies could vary widely. Some of these strains may hinder the efficacy of one medicine, while others may enhance it.
There are too many unknowns to render any given probiotic totally safe, said Dr. Pieter Cohen, an associate professor of medicine at Harvard Medical School and an internist at Cambridge Health Alliance, who wrote about the issue last year in JAMA Internal Medicine.
Probiotics do work for some people, and some conditions: They’re helpful in treating irritable bowel syndrome, for instance, and other gastrointestinal illnesses, said Dr. Rishi Sharma, a gastroenterologist in Walnut Creek, Calif.
Cancer patients often take probiotics to help mitigate some of the side effects of treatment — particularly diarrhea that stems from chemotherapy. While oncologists tend to be loathe to suggest their patients take over-the-counter probiotics, many with cancer still do: The MD Anderson study found that 42 percent of the patients studied were also taking probiotic supplements.
“When you see a study like this, suggesting immunotherapy might not work that well — I’d just avoid taking the probiotic,” Sharma said. “Your whole goal is to treat the cancer. And when it comes to probiotics, there’s just a lot of really bad data out there.”
Immunotherapies generally work in about a quarter of patients with certain cancers, but it’s still unclear exactly why. The MD Anderson/Parker Institute study was designed to probe whether there was a correlation between diet, the gut microbiome, and patient response to immunotherapy.
Forty-six metastatic melanoma patients beginning treatment at MD Anderson were asked to take a survey on what they ate and drank, and what supplements they took. Before the start of the therapy, researchers also took fecal samples from each patient — profiling the bacterial makeup of their respective microbiomes. The study also found that higher fiber intake was correlated with more lush microbiomes — and stronger responses to immunotherapy.
The research was presented as an abstract at the American Association of Cancer Research meeting this week in Atlanta. It hasn’t yet been published in a peer-reviewed journal.
“This study shows you that a patient’s response to immunotherapy is highly modulated by the microbiome,” said Elinav.
Elinav said the findings “are in perfect agreement” with conclusions from his own research: He published a pair of studies in Cell in 2018, finding that probiotic supplements actually decreased the diversity of participants’ microbiomes after they’d taken a course of antibiotics. In fact, the guts of those who took probiotics took much longer than those who did not to fully recover.
The MD Anderson/Parker Institute findings are far from conclusive. Wargo said that she and her team have been expanding the patient cohort being studied; they are also working with Seres Therapeutics, a Cambridge, Mass.-based biotechnology company, on whether bespoke combinations of probiotics might actually improve immunotherapy responses. Still, not all researchers are convinced by the early conclusions.
The Parker Institute is now conducting such a trial in collaboration with MD Anderson and Seres Therapeutics. This randomized, placebo-controlled clinical study is evaluating whether a specially designed oral microbiome pill with specific types of bacteria could positively impact a patient’s response to checkpoint inhibitors.
“I think it’s a provocative finding,” said Dr. Adil Daud, a professor of medicine and director of melanoma clinical research at University of California, San Francisco. “But I still think it’s too early to really conclusively say that probiotics interfere with immunotherapy.”
The trial was too small, and too many variables could have influenced its outcome, he said. Microbiota vary too significantly from person to person, and immunotherapy responses might even vary depending on age, ethnicity, and gender, Daud said. The study was too small to possibly take all of these factors into consideration, he said.
Daud noted that he did have one melanoma patient that he treated with pembrolizumab — an anti-PD-L1 immunotherapy — who actually seemed to benefit from probiotic use. Upon stopping a drug that had proved effective, the patient’s tumor began to grow back. When Daud restarted the pembrolizumab, the patient chose to also take a probiotic from Whole Foods; with the addition of the supplement, the same drug had a lasting effect on keeping the cancer at bay.
“But this is an isolated, n=1 case — so I don’t know how much weight this carries,” Daud said.
Daud tells his patients that, rather than focusing on probiotics, they’d be better served to work on their diet — increasing fiber intake, for instance.
Cohen, the internist at Cambridge Health Alliance, said he “can’t make heads or tails” of the latest study — it’s too small and vague, in his view.
“My two cents would be, this study reminds us that there’s no question that probiotics have a powerful impact on the immune system,” Cohen said. “That, and we have almost no data to demonstrate that these live microorganisms actually improve health.”
Great article! So does it means that Probiotics supplement is not recomended because it can harm a person, especially to a cancer patient? How about organic food that contains a probiotic as well? That is a sort of alarming, particularly for the cancer patient, but a helpful insight for everyone. I found some natural food that contains probiotics, here it is https://activatedyou.com/prebiotics-probiotics-guide/ I don’t know if it safe, but I want to hear some feedback about the food listed in that article. Thank you in advance.
Is this article intended to speak just about probiotic supplements vs. food-based probiotics? Haven’t people been eating cultured and probiotic-rich foods since the beginning of time? In an ideal world supplements could be standardized, with full transparency and indications and contraindications easily researched, while still allowing complete freedom of choice on behalf of the consumer. I don’t know how feasible that would be. Many people panic at the idea that standardization reduces this freedom. Supplements vary widely in price, so are those that are able to spend hundreds of dollars per month on supplements really getting a much better product than someone who can only afford and/or is purchasing the most economic versions?
Regardless, I think any article on nutrients needs to clarify whether it just applies to the “isolated” version of the nutrient as a supplement or the naturally occurring food-based version, as well.
There are so many companies and so much info on pro and cons for taking or not taking certain supplements. There are companies that spend millions on research and have made supplements that are pharmaceutical grade. You need to do your homework. I have changed my health and families and client by recommending good quality whole foods. Organic when possible. I have taken probiotics but only from jone that I trust. I have seen research from scientists from a company I trust that spends millions on research. The proof is in the results. I have seen and heard great results from dozens of people. I am a holistic nutritionist and have read hundreds of articles. Our healthy microbiome is the base for almost everything in the body. To say people can just keep it healthy by eating fruits and veggies. I don’t believe to be true. Especially considering our enviroment, what were are being exposed to in our water foods etc. Animals are getting low dose antibiotics on a regular basis, it is in our water. Eating healthy and as clean as possible and I recommend a top quality probiotic with the two strongest strains. Suggesting a large variety of strains may not stand the acidity of the stomach acid. That is research from 70 top scientists. I find a stick to a couple of good sources and that takes out the confusion of who to listen to.
Recently ended up in emergency experience severe abdominal distress on upper right hand side, dyspepsia, nausea bordering on vomiting. Normal temperature and blood pressure. Hospital thought it might be appendicitis, ruled that out. Did ECG or CT scan (forget which is which). Normal. Total CBC normal. Ultrasound on abdominal normal. Meanwhile, I was in severe abdominal pain whenever I moved, horrible indigestion (which I never get .. I drink tons of water and have a high fibre diet) The pain when breathing deeply was sharp and woke me up in the middle of the night. Ultrasound showed a ton of gas in the stomach. They prescribed an acid reflux type medicine Lansoprazole, because that was the last thing they could ascribe my symptoms to, but I am fairly sure that wasn’t it. I’ve never had problems with acid indigestion and my diet isn’t acidic.
It was only then that I remembered that I had started using a new yogurt on my oatmeal three days prior. Upon further examination I noticed it contained, you guessed it, probiotics. I don’t usually write on these websites, but felt others may want to know. I think probiotics may be helpful for some folks, but feel they should come with warnings about starting with minimum quantities and waiting to see how you react before consuming more. I am on the mend, but still not back to normal yet. I worry that my stomach was damaged but time will prove that out. Needless to say, we threw the yogurt out.
Hello Meghana, that was a very interesting article about the relationship between Probioitcs and the immune system in general.
I am a specialist with nutrition and have written several articles myself on the subject. Very interesting paper and research. I will be very keen to read it.
Thank you for enlightening me about this.
I have worked with probiotics for nearly 30 years, in 100 countries and tried to summarize this in a blog
Thank you so much for the information 🙂 I also take probiotics and it is really helpful to improve my gut.
Hey there! Well, I read this entire article and also a comment by the gentleman named ‘Faryn’ and now I can’t help but think this is a biased piece! I’ve been treating a constipation issue for about 5 years now, and trust me, I’ve read a lot of things on probiotics! I’ve also tried all sorts of OTC probiotics, some of them helped me a little and some of them didn’t help me at all. It’s mostly a matter of finding something that works for you and for what your gut needs! Florajen Digestion was the only probiotic suplement that worked for me! So do your research and learn how to listen to your body!
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