Gut reaction

Fiber is better for immunity than probiotics — study

“Specific and high-dose supplements can have unintended effects.”

Abstract bacteria, probiotics, gram positive bacteria 3d illustration

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Probiotics are big business — they are the third most common supplement, after vitamins and minerals. Some formulas are touted as being good for digestion and the immune system, and they are particularly popular with people worried about immunity. But a new survey of dietary habits and probiotic intake among cancer patients suggests it might be better for immunity to grab a handful of raspberries, crack open a can of black beans, or reach for some other high-fiber food than probiotics.

What’s new — In the observational study, published Thursday in the journal Science, 293 people all receiving similar treatments for skin cancer showed no significant immune boost from taking a probiotic — but eating a diet rich in fiber was correlated to survival.

Further, in an accompanying rodent study, high-fiber diets help lab mice ward off cancer, while probiotics were linked to tumor growth.

Carrie Daniel-MacDougall, director of the M.D. Anderson Bionutrition Research Core at the University of Texas MD Anderson Cancer Center and one of the co-authors, explains the results are reason enough to reconsider probiotics as a harmless supplement.

“This and other studies seem to increasingly suggest that the design and use of probiotic supplements should perhaps be more carefully designed and administered,” Daniel-MacDougall tells Inverse.

How They Did It — The researchers asked 293 people with melanoma (skin cancer) to complete a lifestyle survey, including a record of diet and probiotics use. Eighty-seven percent of the patients received immune checkpoint blockade therapy, a widely used class of medications that can help the immune system detect and attack cancerous cells.

Skin cancer can manifest as melanocyte growths on the skinIrena Sowinska/Moment/Getty Images

Among these, 31 percent had used a probiotic in the last month. Meanwhile, about 29 percent got a sufficient amount of fiber in their diets, measured at 20 grams or more a day.

The researchers found no significant difference in outcomes in progression-free survival for patients who did take probiotics versus those who did not. Participants with sufficient fiber in their diets had better chances at cancer-free survival compared to the participants with insufficient fiber intake.

“As expected, dietary fiber intake was highly correlated with fruit, vegetable, legume, and whole grain intake and, to a lesser extent, with calcium intake,” the study states.

The very best results were in people with sufficient fiber and no probiotic use.

Digging into the details — The researchers used mice to validate the effect of probiotics or sufficient fiber intake seen in the humans. All the mice were given skin cancer tumors and then treated using an analog to the human immune checkpoint blockade therapy.

In one study, the mice were separated into two groups: a group that consumed a commercially purchased probiotic and another a placebo. In the second, mice were separated by fiber-rich and fiber-poor diets.

In the mice: A high-fiber diet also seemed to help the mice fight cancer.

“Mice receiving a fiber-rich diet demonstrated delayed tumor outgrowth compared with mice who received a fiber-poor diet,” the study reports.

Those receiving probiotics did worse than mice that received none.

They “had significantly larger tumors compared with control mice,” the study notes.

Why It Matters — Probiotics are staple supplements in bathroom cabinets everywhere. Part of this is to do with an uptick in research into the microbiome, the ecosystem of microorganisms within the human body, fueling buzz around “good bacteria.” But while the microbiome’s effect on health is slowly being teased out, probiotics have not been well-studied.

There is a perception that probiotics aren’t harmful for the people who have the most reason to consider trying them out — those afflicted with chronic diseases, says Daniel-MacDougall.

“[T]here is the conception that supplements, in general, are safe and worth trying them to see if they help,” she says.

“However, we know from other fields, like nutrition, that specific and high-dose supplements can have unintended effects or consequences under various conditions,” she adds.

This gels with the opinion in a March 2021 review, published in Frontiers in Oncology:

Although the use of probiotics has been widely popularized in the public, the results of many probiotic clinical trials are contradictory. Particularly in cancer patients, the feasibility of probiotic management providing benefits by targeting cancer and lessening anticancer side effects requires further investigation.

On the flip side, high-fiber foods don’t get enough hype; only five percent of Americans get the National Academy of Medicine’s recommended daily allotment of fiber — 20 grams a day. That’s three bananas, or a few cups of berries.

One cup of berries has eight grams of fiberOscar Solano Tejada/Moment/Getty Images

What’s Next — This was an observational study and it has some limits:

“Numerous challenges exist to decipher how best to leverage the microbiome to optimize patient outcomes,” the authors state.

One of the other co-authors, Jennifer McQuade, who studies melanoma at the University of Texas, tells Inverse she is in the early stages of an intervention study “in which all food is provided to patients over the duration of the study.”

It will measure the effects of “two different healthy diet interventions with varying fiber contents in melanoma patients receiving immunotherapy,” she says.

McQuade adds: “The key question for patients who have a new diagnosis of melanoma and are starting immunotherapy is: ‘Will changing my diet improve my microbiome and improve response to immunotherapy?’ This is the critical question we are trying to address.”

Abstract:
Gut bacteria modulate the response to immune checkpoint blockade (ICB) treatment in cancer, but the effect of diet and supplements on this interaction is not well studied. We assessed fecal microbiota profiles, dietary habits, and commercially available probiotic supplement use in melanoma patients and performed parallel preclinical studies. Higher dietary fiber was associated with significantly improved progression-free survival in 128 patients on ICB, with the most pronounced benefit observed in patients with sufficient dietary fiber intake and no probiotic use. Findings were recapitulated in preclinical models, which demonstrated impaired treatment response to anti–programmed cell death 1 (anti–PD-1)–based therapy in mice receiving a low-fiber diet or probiotics, with a lower frequency of interferon-g–positive cytotoxic T cells in the tumor microenvironment. Together, these data have clinical implications for patients receiving ICB for cancer.
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