New knowledge on human microbiome begins to impact practice

The first annual Dr. Ananda Prasad Lecture in Physiology highlighted the role of the human microbiome in health and disease.

Vincent B. Young, MD, PhD, connected the dots between physiology and clinical medicine at the first annual Dr. Ananda Prasad Lecture in Physiology on Friday.

“As a practicing clinician, you are touched upon by basic and translational research, and what you observe in the day-to-day care of patients informs both of those as well,” he said.

Dr. Young spoke about one of the most recent and highly publicized physiological discoveries to date: the human microbiome and its role in health and disease. He noted an exponential increase in the use of the word “microbiome” in the scientific literature and the lay press.

“Clinicians should think about this, not necessarily how it affects your day-to-day practice now, but how it may affect it more in the future,” said Dr. Young, a professor in the departments of internal medicine/infectious diseases and microbiology and immunology at the University of Michigan Medical School in Ann Arbor.

The microbiome is defined as the total community of microbes (e.g., bacteria, fungi, and viruses) and the given environment they inhabit, such as soil or the human body, he explained.

“The physiology of this community is very tied with our own physiology. … The number of genes inside these thousands of different types of microbes in you actually has a metabolic capacity that outstrips our own metabolic capacity by, depending on whose [estimates] you believe, at least an order of magnitude—maybe even two or three orders of magnitude,” Dr. Young said.

There are caveats to microbiome research, however. Researchers can study microbiota of different individuals in great detail and find differences between them, “but just because we see those differences, we don't know what the causation is,” Dr. Young said.

Despite the challenges of microbiome research, recent years have brought evidence in the fields of infectious diseases, cardiology, pharmacology, oncology, and endocrinology, he noted. Perhaps the most well-known impact of manipulating the human microbiome is in cases of recurrent Clostridium difficile, Dr. Young said.

When he asked the audience how many physicians have referred a patient with C. difficile to receive fecal microbiota transplant (FMT), many hands went up in the air. “That's pretty significant. If I had asked this five years ago, I'd probably, first of all, get a lot of weird looks, and then probably only a few hands [would] go up,” said Dr. Young.

A clear shift happened in 2013, when a randomized controlled trial of FMT, published in the New England Journal of Medicine, saw positive results and was stopped early, he noted. “A lot of our interest in FMT came from this initial paper that only had 14 patients who got active treatment. … We've had a lot more studies now, and there was a recent meta-analysis that again backs this up. FMT has a much higher success rate for treating recurrent C. difficile infection as opposed to standard therapy, vancomycin,” he said.

How does this happen? “We assume we're restoring the microbiota,” said Dr. Young.

As researchers discover more and more associations between the status of the microbiome and various states of health and disease, physicians grow closer to the aim of precision health and providing customized care to patients, he said.

“We are just beginning to move from these associations to causation,” Dr. Young said. “Once we understand some of this causation and understand the structure and function of the microbiome, perhaps we can move to the point where we can intentionally manipulate the microbiota to … prevent and treat diseases.”