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Revealing secrets of the microbiome

Medicine@Yale, 2019 - June July


Goodman finds that gut organisms are responsible for more than digestion

In ecology, the branch of biology that investigates how organisms relate with each other and their environment, the points of interaction seem infinite. Those points riveted Andrew Goodman, PhD, C.N.H. Long Professor of Microbial Pathogenesis, as he grew up near Portland, Oregon, and continued to absorb him throughout his undergraduate studies in ecology and evolutionary biology at Princeton University.

Toward the end of his time in New Jersey, intricate ecosystems of a different sort—communities of bacteria—caught Goodman’s attention. “I realized that microbial communities can be viewed as ecological systems that allow us to test our ideas in a way that is very hard to do in other environments,” Goodman says.

His academic interests instantly took a sharp turn. He shifted from a broad study of ecology that included tracking tigers in their natural habitat, to a focus on molecular biology. He began studying bacterial genetics for his graduate work at Harvard Medical School. “I’ve been fascinated with this intersection of ecology and mechanisms—the genes, pathways, and molecules—for 20 years,” Goodman says.

During his postdoctoral studies at Washington University School of Medicine in St. Louis, Goodman decided to focus on the bacterial communities that live in humans. He worked to bring techniques that were initially developed for studying disease-causing bacteria to the then-new field of the human microbiome, and developed new approaches of his own. “The discovery that commensal bacteria are equipped with numerous specialized adaptations to live in the gut changed the way I thought about the microbiome,” he says.

In 2010, when Yale offered Goodman an opportunity to join the newly formed Microbial Sciences Institute on Yale’s West Campus, he did not hesitate. Goodman saw the “West Campus idea”—to bring together researchers from different departments that would normally be separated into different buildings or campuses—as especially advantageous for addressing the challenge of understanding microbial diversity. In this environment, Goodman and colleagues collaborate with ecologists, chemists, and geneticists. In Goodman’s view, “What Yale has built at West Campus is truly unique in this regard. We get the chance to see more different approaches to thinking about microbes than you would at any other university in the country due to the proximity of different specialists.”

When Goodman came to Yale, he says, “these ideas were mainly aspirational, but I think our research validates and extends this vision.” His lab currently works to bring together ecology and microbiology to understand how gut microbial communities form and persist—despite sparse resources, attacks from the immune system, and even warfare between commensal bacteria themselves.

His lab’s second research focus directly translates to human health: how microbes affect a person’s response to drugs. “If we understood the link between a person’s microbiome and their drug response, we could select the dose, delivery route, or specific drug that would be most likely to succeed,” Goodman says. In this area, the group has made recent progress. In research published in February in the journal Science, Goodman’s lab showed that gut bacteria can play an enormous role in producing toxic drug metabolites, in certain cases having a larger adverse impact than the liver. These hidden activities of our gut microbes could prevent drugs from achieving their intended benefits and even can cause harm to the patient.

During his time at Yale, Goodman’s bold strokes of scientific inquiry have been recognized with a Presidential Early Career Award for Scientists and Engineers, a National Institutes of Health Director’s New Innovator Award, and a Howard Hughes Medical Institute Faculty Scholar Award. Goodman appreciates how important his lab team’s contributions have been. “I’ve been very lucky to have wonderful postdocs, research scientists, and students join our research group, and I feel privileged to get to work with this team,” he says.

While these are still early days for his laboratory’s newest initiatives, Goodman says he hopes to contribute to answering the basic question of how microbes recognize drugs. “We don’t know whether microbes have a few enzymes that target many drugs, or if it’s more one-to-one,” he says. But knowing those answers could lead to exciting new therapies. “I think it’s safe to predict that we will be temporarily and reversibly changing people’s microbiomes before we’re changing their genomes.”