Researchers found that a non-absorbed antibiotic can trigger gut bacteria to make longevity-promoting compounds.
A research team has discovered a method for turning the bacteria that live in animal digestive systems to function like miniature factories capable of generating compounds that support longer life in their hosts, showing a potential new direction for drug development.
Janelia Senior Group Leader Meng Wang and her colleagues focus on the biology of aging, and they wanted to explore how their discoveries about longevity-enhancing compounds might be applied in real-world settings.
One approach they pursued involved encouraging the gut microbiota (the diverse community of bacteria in the digestive tract that produces numerous chemical substances) to make metabolites that positively influence the animals they inhabit. Their initial target was colanic acid, a gut bacterial compound previously shown to extend lifespan in roundworms and fruit flies.
In new research, Wang’s team shows that bacteria overproduce colanic acids when exposed to low doses of the antibiotic cephaloridine, and roundworms treated with cephaloridine lived longer.
Effects Observed in Mice
In mice, low doses of cephaloridine induced transcription in a portion of the gut bacteria’s genome responsible for synthesizing colanic acids. This resulted in changes in age-related metabolic changes in the animals: increases in good cholesterol and decreases in bad cholesterol in males and reductions in insulin levels in females.
Because cephaloridine does not get absorbed by the body if it is ingested orally, the antibiotic induces changes in the gut microbiome without affecting the rest of the animal’s body, eliminating side effects and toxicity.
The researchers say the new work highlights a promising path for leveraging bacteria-targeting drugs to promote longevity. They hope it can also inspire a new way of thinking about drug development. Rather than developing drugs that target the body directly, the research suggests scientists could potentially design compounds that target the microbiota, inducing changes that enable them to produce compounds beneficial to their host animals.
Reference: “Chemical modulation of gut bacterial metabolism induces colanic acid and extends the lifespan of nematode and mammalian hosts” by Guo Hu, Marzia Savini, Matthew Brandon Cooke, Xin Wei, Dinghuan Deng, Shihong M. Gao, Ruyue Alps Xia, Youchen Guan, Alice X. Wen, Xin Yu, Jin Wang, Chao Jiang, Christophe Herman, Jiefu Li and Meng C. Wang, 11 November 2025, PLOS Biology.
DOI: 10.1371/journal.pbio.3002749
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