The Human Microbiome: Promise and Pitfalls

Spoiler alert: This story about the miraculous medical potential of the human microbiome is going to end with some big unknowns and be served up with a side of guidance to eat more fermentable fiber.

New discoveries about the microbiome — the trillions of microorganisms that inhabit the body and interact with its cells — are piling up rapidly and may impact every aspect of medical practice in the coming decades. However, they have so far resulted in only one reliable cure, for a stubborn bacterial infection, despite a proliferation of over-the-counter “probiotics” promising smoother digestion, a stronger immune system — even a better mood. Experts say that while there are many encouraging research avenues, most microbiome-related product claims should, for now, be taken with a grain of salt (or maybe a bowl of chili).

Each person’s microbiome is a unique collection of mostly bacteria, along with some fungi, viruses and other microorganisms. Estimates of the microbiome’s size vary wildly, but conservatively, it equals the number of cells in the body (some 38 trillion in a 155-pound person, though all those microbes weigh only about half a pound).

[See: 10 Weird Things That Can Make You Poop. ]

Off-kilter. A healthy microbiome is required for the body to function properly. Research associates microbiome disruptions with diseases and chronic ailments that plague millions: celiac disease, asthma, allergies and even colon cancer. Many people experience temporary digestive chaos from antibiotics that attack good gut bacteria along with their intended targets, and some studies show that just one course of antibiotics can change the gut microbiome for months.

“We have good evidence that these microcolonies are essential to our biology,” says Jens Walter, professor of agricultural, food and nutritional science at the University of Alberta. “We exist in a state of symbiosis with these communities, and what we do in modern life disrupts this symbiosis.” Walter has been studying the microbiome since 1999 and has recently been exploring how it might be implicated in multiple sclerosis. Studies have shown differences in the gut microbiome of people with and without MS.

The federal website, where researchers must register medical studies, lists almost 1,500 microbiome-related research projects in various stages, and the National Institutes of Health’s Human Microbiome Project has a library of over 32,000 microbiome samples available for study.

While the body has distinct microbiomes at different sites — for example, in the mouth and nose and on the skin — the one that’s most often in the limelight is the gut microbiome, which aids digestion and secretes chemicals that travel through the bloodstream to all parts of the body.

“There are studies that link the microbiome with everything from autism to Alzheimer’s,” says Thomas Schmidt, head of the Michigan Microbiome Project at the University of Michigan–Ann Arbor, created to study how to engineer the gut microbiome to improve human health. “However, some of those relationships will be causal and others will just be coincidental, and we are in the stage of figuring it out.” Gut bacteria aren’t just active in the gut, he points out: The chemicals they create affect every aspect of our physical and mental health, and we’ve evolved to need those chemicals.

Schmidt studies one in particular called butyrate, made by bacteria in the large intestine. Butyrate is a preferred energy source for cells that line the intestine. The body can’t make its own butyrate and counts on gut bacteria to do that job using fermentable fiber, which can’t be broken down by the human digestive system. When cells don’t get enough butyrate, they can malfunction and cause inflammation in the surrounding tissue, which may affect the body’s other systems, too. That’s why Schmidt encourages people to eat more fermentable fiber. Foods high in it include most fruits and vegetables, beans, oats and barley.

[See: 8 Food Trends Nutrition Experts Pray Will Never Return.]

Friend or foe? Society has long villainized bacteria. Some types are harmful, of course, and the discovery of penicillin and other antibiotics has largely freed us from the epidemics they cause. But in our zeal to wipe them out, with antibacterial drugs, soaps, hand sanitizers and household cleaners, we inadvertently damage the good ones.

Dosing with antibiotics is the most obvious way to eradicate good bacteria, an excellent reason why doctors decline to prescribe antibiotics unless they’re sure patients have a bacterial infection that really requires them. But anything people eat, drink or absorb through the skin can also change the microbiome. For example, studies of the common herbicide glyphosate suggest that it may alter the microbiome of bees and the gut microbiome of baby rats.

Perhaps the most widespread potential symptom of microbiome upheaval is the obesity epidemic, which afflicts almost 40% of U.S. adults. While the relationship is still unclear, researchers have found differences in the microbiomes of people with and without obesity. Infectious disease specialist Dr. Martin Blaser, who wrote “Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues,” believes many of today’s major health ills, especially obesity, asthma and allergies, can be traced to microbiome disruptions caused in part by overreliance on antibiotics. He cites a Danish study suggesting that each course of antibiotics boosts the risk of developing inflammatory bowel disease during childhood by 14%.

The microbiome affects, and is affected by, medications in other ways, adds Blaser, director of the Center for Advanced Biotechnology and Medicine at Rutgers University: “If you give 100 people a drug, some will get better, some won’t and some will get sick from it, and a big source of this variation has to do with the microbiome.” Blaser expects that as we gain a more sophisticated understanding of this relationship, microbiome analysis will become part of choosing which drugs — and doses — are best matched to a patient’s unique biology.

The only major microbiome development that’s found a place in clinical practice is a fecal transplant to treat Clostridioides difficile, the stubbornly antibiotic-resistant and sometimes deadly bug known as “C.diff,” which sickens almost half a million people each year, often during hospital stays when antibiotics weaken their native microbiomes.

A fecal transplant is just what it sounds like: Stool samples from a healthy volunteer are introduced into the infected person, either via the colon or swallowed in capsule form. The beneficial bacteria in the sample colonize the patient’s intestines, displacing the harmful C. diff bacteria. Research suggests the treatment ousts the infection in up to 90% of patients after antibiotics have failed. “Fecal transplants have become the state of the art,” Blaser says. “Thirty years ago if you told someone, ‘We’ll give you feces!’ they would have laughed, but it’s clearly correct.”

Proceed with caution. The Food and Drug Administration still considers the treatment experimental and hasn’t approved it for any use. But because fecal transplants have shown success against intractable C. diff. infections, the agency is not actively preventing them from being used in such cases, provided patients are aware of the risks and certain precautions are followed. The FDA updated those precautions in June to include additional testing of stool donations, following news that a patient had died after receiving a fecal transplant containing a drug-resistant strain of E.coli.

The promise of improving health with “natural” microbes has caused an explosion of “probiotic” products that often boast of containing multiple strains of beneficial live bacteria. Amazon alone stocks more than 3,000 probiotics.

But beware, says dietary supplement expert Dr. Pieter Cohen, assistant professor of medicine at Harvard Medical School and an internist at Cambridge Health Alliance. “Each live bacterium or fungus needs to be understood on its own,” he says. “If there is research to suggest that a specific strain of a microorganism can be helpful in a specific clinical situation, then that specific strain should be the only live organism used to treat the condition.”

[See: 8 Myths About Constipation.]

No evidence. Cohen is concerned that probiotic makers aren’t required to label their products transparently — with the strain of bacteria and the amount. Thus, consumers have no way to compare different probiotics or even be certain what’s in them. “There is no evidence that all the different microorganisms sold as ‘probiotics’ in the U.S. are interchangeable, or even that they are beneficial.”

Blaser agrees. “They are almost completely untested,” he says. “The number of robust clinical trials is small. People are making money from these products, so why would they do a test that impedes their ability to make money?”

Recent studies suggest that OTC probiotics may affect the immune system unpredictably; one found that cancer patients taking probiotics didn’t respond as well to immunotherapy as those who weren’t.

Don’t expect guidance from the FDA, at least for now. Close reading of probiotic labels reveals the products haven’t been evaluated by the agency nor are they intended to “diagnose, treat, cure or prevent any disease.” While the FDA is studying specific applications of specific organisms, it has not “approved any probiotic as a live biotherapeutic product,” per a 2018 agency statement.

To nurture his gut microbiome, Schmidt focuses on upping his fermentable fiber and avoiding antibiotics generally. If he were facing hospitalization and the prospect of intravenous antibiotics, he says he’d store a fecal sample in the freezer to preserve his pre-hospital microbiome. “If I got a C.diff infection and needed a fecal transplant, I’d rather have my own bacteria, which work well in my body and are distinctive.”

These moves may seem modest, given all the promise. But stay tuned, says Blaser: “The microbiome is a scientific and a medical frontier. I think a generation from now it will touch all areas of medicine.”

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