Can Understanding the Gut Microbiome Improve Clinical Oncology?

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Researchers hope to define what constitutes a functionally healthy microbiome not just in cancer, but across the health spectrum.
Researchers hope to define what constitutes a functionally healthy microbiome not just in cancer, but across the health spectrum.

After completion of the Human Microbiome Project, researchers began untangling the genetics of a dizzying array of bacteria and other microbes that live inside us. Their goal is to gauge the bacteria's impact on human health.

Using the breakthrough technology of DNA sequencing, scientists are identifying millions of genes and thousands of different species, so far, that make up our microbial universe — a diverse collection of bacteria, viruses, fungi and single-celled microorganisms — residing in, or on, the human body.1

“The microbiome is a complex, metabolic organ system, equivalent to the liver,” says Lita Proctor, PhD, coordinator of the National Institutes of Health's decade-long project, which officially ended in September. ”We're now trying to make better sense of it,” she says, by analyzing how microbes interact and communicate with each other, the environments they live in, and their human hosts.

Surprisingly, perhaps, beneficial bugs vastly outnumber those causing disease, Dr Proctor said. Harmless microbes are known to perform many vital bodily functions, from synthesizing vitamins and metabolizing drugs to acting as molecular decoys in breast milk to protect infants from potentially harmful bugs.2

In oncology, several recent studies showed that the presence or absence of particular bacteria in the gut may determine how well some patients respond to immunotherapy. The studies, widely viewed as important steps towards eventual clinical use, are, however, small and retrospective.

Interest in the microbiome and its potential to transform medicine is accelerating, according to Dr Proctor, “attracting a tremendous amount of attention at very early stages of development.”

Numerous companies are trying to develop microbiome products, she says, which are “springing up like wildflowers.”

Seres Therapeutics, which is based in Cambridge, Massachusetts, announced in November that it hopes to launch a clinical trial, possibly within the next 6 months, to test its oral microbial therapy in patients with advanced or metastatic melanoma. The company partnered with MD Anderson Cancer Center in Houston, Texas and the Parker Institute for Cancer Immunotherapy in San Francisco, California, to move the therapy forward.3

The trial's design will rely on the research of Jennifer Wargo, MD, an associate professor of genomic medicine and surgical oncology at MD Anderson, and her colleagues, who showed that some types of bacteria in the gut improve patient response to anti-PD-1 checkpoint inhibitors, while others tamp down the response. Results of their work were published in Science last November.4

Deciding which bacteria to study, Dr Wargo says, came not from her team, but from patients themselves after researchers profiled their oral and gut bacteria. While no differences were seen between responders and non-responders in oral bacteria, she says, differences in the gut bacteria were “like night and day.” Not only did patients with diverse bacterial populations do much better on immunotherapy than those lacking diversity, Dr Wargo says, the composition of the bacteria — the number of a specific bacteria type — mattered as well.

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