In rare feat, researchers decipher how one gut bacterium influences immunity

From immunity to metabolism to mental health, it seems like the gut microbiome has been linked to every aspect of human health and disease.

But with hundreds of bacterial species populating our gastrointestinal tract, it’s a daunting task to pinpoint which molecules made by which bacteria affect which biological processes — and how they do so.

“Microbiome studies need to move from making associations to determining function and causation,” said Ramnik Xavier, the Kurt J. Isselbacher Professor of Medicine in the Field of Gastroenterology at Harvard Medical School and Massachusetts General Hospital, a core institute member at the Broad Institute of MIT and Harvard, and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.

Such knowledge is essential for learning how to manipulate gut bacteria to treat or prevent illness.

A team led by researchers at HMS and the Broad has just accomplished the rare feat of connecting those dots for one important gut bacterium.

“The real significance of this work was connecting a bacterium, the molecule it makes, the pathway it operates through, and the biological outcome,” said Jon Clardy, the Hsien Wu and Daisy Yen Wu Professor of Biological Chemistry and Molecular Pharmacology in the Blavatnik Institute at HMS and co-senior author of the study with Xavier. “That’s very rare.”

Clardy, Xavier, and colleagues focused on Akkermansia muciniphila, a species that accounts for an impressive 3 percent of the gut microbiome. It gets its name from the intestinal mucus it breaks down.

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