Microbiome Matters

“The landscape of clinical microbiome research has dramatically evolved over the past decade.” 

Jack A. Gilbert, PhD, Professor, Department of Pediatrics, University of California, San Diego, Director Microbiome and Metagenomics Center and the Microbiome Core Facility, Scripps Institution of Oceanography

“We are on the cusp of a new era. Like when humans first discovered insulin and glucagon were hormones that impact sugar metabolism. We now recognize myriad new ‘hormones’ in the form of gut microbiome metabolites that impact our physiology and susceptibility to diseases.”

Stanley Hazen, MD, PhD, Director, Center for Microbiome & Human Health, Cleveland Clinic, Cleveland, Ohio

Researchers from diverse fields have been working hard to establish the impacts of the microbiome on human health and disease. The fruits of their investigations are too numerous to mention in this week’s post. (For a thorough review, see, Gilbert, Jack A., “Clinical translation of microbiome research,” Nature Medicine, April 11, 2025). Hence, what follows is my assessment of some of the most interesting discoveries in the area since my last post on this topic. (See, “The Microbiome Revolution,” Germ Gems, January 10, 2024).

The human microbiome: a recap. The simplest definition of the human microbiome is the microbes that share our bodily surfaces. At the turn of this century, Nobel laureate Joshua Lederberg coined the term “microbiome.” But many of the key concepts regarding the microbiome’s importance can be traced to the late 19th century when another Nobel laureate, Elie Metchnikoff, a visionary scientist who is considered the father of cellular immunology, recognized that an imbalance of harmful versus beneficial bacteria in the human gut could result in a condition he called dysbiosis. (Metchnikoff promoted the idea that certain kinds of bacteria found in yoghurt could restore the gut’s microbiome to a state of eubiosis.)

In 2007, the National Institutes of Health launched the “Human Microbiome Project” (HMP). This was a huge step for human microbiome research. This project is aimed at a comprehensive characterization of five human microbiomes: gut, oral cavity, lungs, skin, and vagina, with the goal of defining their role in human health and disease.

DNA sequencing and metagenomics revolutionized the characterization of the human microbiomes by allowing researchers to study microbial communities in detail, identify previously unknown species and understand their functions. Suffice it to say, the findings of the HMP researchers are mind-blowing.

Of the five human microbiomes, the gut microbiome has captured the most attention. (Given its numerous bidirectional interactions with the central nervous system, it’s not surprising it’s considered by some as a “second brain.”) Most studies of the gut microbiome have focused on the bacterial residents. But the gut is also home to an even greater number of viruses (the virome), as well as a huge number of fungi (the mycobiome).

The gut has 10x the number of microbes than cells in the entire human body, totaling roughly 100 trillion microbes, representing as many as 5,000 different species and weighing approximately 2 kilograms (4.4 pounds)—slightly more than the adult human brain which weighs about 3 pounds. “If [one] could line the microbes from a single person’s gut up end to tend, they would be able to circle the Earth two and a half times.”  (Robinson, Jake M., Invisible Friends: How Microbes Shape Our Lives and the World Around Us).

Impact of the gut microbiome on human health and disease. Researchers from almost every medical discipline have been exploring the potential role of the gut microbiome in diseases or disorders for which improved therapies are sorely needed. These diseases or disorders include cancer, obesity/weight loss, a whole host of neurological conditions such as multiple sclerosis,  Parkinson’s disease, Alzheimer’s disease, sleep disorders, chronic pain, autism, and neuropsychiatric  conditions (schizophrenia, depression, major anxiety disorder, and illnesses related to emotional stress), and, of course, infectious diseases.

In the field of infectious diseases, many researchers have focused on the effects of antibiotics on the gut microbiome because most, if not all, of these drugs alter the gut microbiome. Multiple studies of antibiotic use in childhood, for example, have shown an increased risk of asthma, food allergies, and certain intellectual disabilities.

Infectious diseases specialist Dr. Martin J. Blaser has led the way in defining the impact of antibiotics on the microbiome. In his seminal book Missing Microbes: How the Overuse of Antibiotics Is Fueling our Modern Plagues, he stated,

“It should be clear by now that even short-term antibiotic treatments can lead to long-term shifts in the microbes colonizing our bodies. A full recovery or bounce-back of healthy bacteria is in no way guaranteed, despite the long-held belief that such was the case. But that is not my only worry. I also fear that some of our residential organisms—what I think of as contingency species—may disappear altogether.”

Commensal bacteria that colonize the lower gastrointestinal tract protect us against invasive, disease-causing pathogens, a phenomenon referred to as “colonization resistance.” Antibiotics that disrupt the gut microbiome can cause Clostridioides difficile colitis (or “C. diff”) when the antibiotics deplete the microbiome of friendly constituents and allow C. difficile to flourish. In the U.S., an estimated 30,000 deaths annually are associated with C. diff infections.

Fecal microbiota transplantation (FMT) is one of the most effective methods to treat C. diff. (See, “Has Fecal Microbiota Transplantation for Recurrent C. diff  Colitis Pooped Out?,” Germ Gems, October 30, 2024). A recent clinical trial again supports the efficacy of FMT for this potentially life-threatening condition, but from this study it appears the fecal sample needs to be administered via colonoscopy rather than rectally to be effective. (See, “Fecal Therapy via Colonoscopy Found Safe and Effective for Recurrent C. diff,” MedPage Today, May 5, 2025).

To make treatment considerably easier, Vowst, an oral Federal Drug Administration (FDA)-approved fecal-derived product, is available for prevention of recurrent C. diff.

The microbiome craze. While there’s been an amazing proliferation of research showing how the microbiome impacts human health, there’s also been a proliferation of companies selling dietary supplements, meal replacement shakes, personalized diet management, and at-home microbiome tests claiming that these products or tests improve gut health.

For example, there are companies selling gut microbiome tests directly to customers asserting “that they can improve gut health by offering individuals personalized treatments based on their gut microbiome test results.” (See, Larkin, M., “Are Direct-to-Consumer Microbiome Tests Clinically Useful?,” Medscape,  April 24, 2024).  But as Dr. Colleen R. Kelly warned, “[T]hese tests are not validated and are clinically meaningless and not worth the money. There is a reason they are not covered by insurance.”

At present, there is no test that can reliably tell anyone the state of health of their gut microbiome. Moreover, “[t]here is no clear guidance for healthcare professions to look at regarding the importance and influence of the gut microbiota in gut health.” (See, Thwaini, H., “How Should Doctors Handle the Microbiome Craze?,” Medscape UK, March 20, 2024). So, what’s a physician to do?

A physician, or, for that matter, everyone should first and foremost use common sense. When you see an alluring claim that a drug or natural product might improve your gut health, your first question should be: “What’s the evidence?”

For American physicians, this means finding out if the claim is backed by FDA approval.  Currently, this is becoming a more thorny issue, given cutbacks of federal support of the FDA. Yet, the FDA remains the pivotal resource regarding the safety and efficacy of drugs. (Neither probiotics nor prebiotics are classified as drugs, and none is FDA-approved for any specific medical indication.)      

Despite the current “craze,” the microbiome may not be the solution for everything. Nonetheless, I would like to be around to see the day when alteration of the gut microbiome is established as treatment of a number of incorrigible diseases. Unfortunately, it appears my gut microbiome is working against me. (See, Lawton, G., “The shocking discovery that our gut microbiome drives ageing,” New Scientist, February 5, 2025).

An after thought. In his 1908 book The Prolonging of Life, Elie Metchnikoff, who is also considered the founder of gerontology, proposed that our lives may be shortened by “chronic poisoning from an abundant intestinal flow.” Which leaves me to question whether the discovery that our gut microbiome drives ageing is all that “shocking.” But, as my editor would say, that’s just me.