Elucidating the role of gut microbially produced hydrogen sulfide in metabolic flexibility and aging

A hallmark of aging is the decline in the ability to adapt to nutrient availability (metabolic flexibility). While gut microbes are linked to health, their role in aging is understudied.

Hydrogen sulfide (H2S), produced by both the host and microbes, modulates metabolism but decreases with age, though therapeutic restoration shows promise. Despite high gut H2S levels, the role of microbial-H2S in metabolic flexibility and aging remains unknown.

I will elucidate the effects and targeted pathways of microbial-H2S by using the metabolically flexible thirteen-lined ground squirrels (TLGS), which enter torpor—an extended state of fasted hibernation with reduced metabolism (~95%)—and the short-lived, genetically modifiable Caenorhabditis elegans, in the Mair and Krautkramer labs at Harvard T.H.

Chan School of Public Health.

During torpor, TLGS have gut microbial shifts similar to fasted humans, with increased H2S-producing sulfate-reducing bacteria (SRB). Elevated torpid liver H2S levels suggest that H2S travels from the gut to the liver.

In C. elegans, H2S is required for extended lifespan under dietary restriction by modulating conserved metabolic pathways.

Thus, I will use (1) TLGS to determine the contribution SRB-H2S to liver metabolic flexibility, and (2) C. elegans to identify evolutionarily conserved age-related metabolic pathways modulated by SRB-H2S.

By supplementing or depleting SRB, I will contribute to understanding the role of SRB in metabolic flexibility and aging.