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.

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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.

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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.”

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  • This is an alarming report since there are thousands of patients on immunotherapy who may be negatively affected by OTC probiotics.

  • Perhaps StatNews should post brief civility guidelines at the beginning of each Comment section suggesting people write after they have had a good night’s and proper nourishment, as if they were speaking to a friend and hoped to change their mind…

  • Excellent comment, Karli. It’s like if I said your backyard needs rodents. How would you know if I was proposing to sell you mice, gophers, moles, or squirrels? Or which ones would be beneficial? And if your backyard already has rodents, how do you know I’m not going to upset whatever ecological balance they’ve already got? If you’re foolish enough to pay me for these rodents, it’ll serve you right if I bring over a cage full of rats.

  • So, instead of making blanket statements, why don’t you try to investigate which strains benefit certain conditions/treatments and which ones are detrimental? Also, you can’t lump all probiotic supplements/companies together and get accurate results in a study. Some of them are more reputable and more consistent than others.

  • I am always looking for the research for everything. Yet I have a complex situation with my “gut;” it’s a genetic problem for a number of my family members. I was hospitalized four different times because of how badly I was with symptoms that I could not control. My cousin had the same problem, we both had the identical symptoms at the same time and for the same period of our lives, whilst we were both in hospital.

    I stopped taking the probiotics plus, that I always purchased at the best pharmacy ever; a privately owned compounding pharmacy where they only have the best quality of their supplements, especially.

    I am still having some issues from time to time. My awesome cousin was doing well too, until he suddenly was not. I was waiting for my physician to come and release me from hospital. Just prior to his entering my room, I received an email from from my cousin’s wife, requesting that we all pray for my cousin to pass peacefully.

    He had melanoma, I did not. When my physician entered my room, my husband and I were both so deeply upset about our loss of another family member who died long before his time. My physician was a great comfort, reminding me that I did not have any signs of melanoma, and reinforced my decision to stop
    using probiotics.

    My own experiences, yet I had already read about the countless individuals who stopped using probiotics, and they had all improved significantly.

    I am only sharing my story, because I am not going to recommend anyone else to do what I did. I strongly recommend that anyone who is using probiotics to have a discussion about this with their own physicians.

  • People, calm yourselves down and go to the literature. These conclusions aren’t published, let alone published in a peer-reviewed journal. There are also no trials listed in ClinicalTrials.gov on probiotics and melanoma for Dr. Wargo. The latest work from this group is here (Nat Med. 2019 Mar;25(3):377-388. doi: 10.1038/s41591-019-0377-7. Epub 2019 Mar 6) and here (Lancet Oncol. 2019 Feb;20(2):e77-e91. doi: 10.1016/S1470-2045(18)30952-5). STAT just did a crap job reporting the studies.

    • Emily, thanks for a useful comment, but I don’t think it’ll “calm down” people who get results from certain probiotics, or have seen loved ones suffer from chemo treatments of which the right probiotic(s) can alleviate side effects. Chronic disease and pain are hell to live with. We take what we can get! And don’t like to to lose it.

  • What sheer arrogance these so-called scientific researchers exhibit. And naturally they are in the management of oncology patients. Why do they not tell the truth about survival rates overall in oncology after they poisoned their hopeful patients. Rather disturbing low figures with people at the end of their lives suffering terribly at the hands of these exclusive hypocrites. Yes there is a place for pharmaceutical intervention in cancer patients. So is there for a number of other modalities. Blatantly attacking probiotics in this pathetic way, shows how little they really care. There are numerous peer-reviewed articles about the microbiome and all related issues. One does not need this opinionated nonsense from these “scientists”.

    • Well, they *are* scientific researchers, and that means they’ve been through rigorous training. However when I found and read the original abstract of their presentation I discovered that all but two of the many contributors worked for Big Pharm. So this is not disinterested academic science. It’s too bad that in the US, medical research has to lead to a patent to pay for itself. It’s hard to patent a naturally occurring substance like turmeric (effective anti-inflammatory and helpful for digestion, according to studies in countries where medical research is government-subsidized) or probiotic strains (available in live cultures in kefir, miso, some yoghurts, home-made pickles, kimchee), or tincture of ginger (powerful aid for nausea and migraine). We need more disinterested research into these things, but I fear we aren’t going to get it from scientists working companies selling the expensive alternatives.

    • @Pieta, here’s what a rational response to this study looks like.
      “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.”
      For an irrational response filled with logical fallacies, read your comment again.

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