Researchers report that small doses of the antibiotic cephaloridine can prompt certain gut bacteria to increase production of colanic acid, a microbial polysaccharide previously tied to longer lifespan in laboratory animals. In experiments, treated roundworms lived longer and mice showed shifts in cholesterol or insulin measures associated with aging, with the team arguing the approach works by acting in the gut rather than throughout the body.
A research team led by Meng C. Wang, a senior group leader at the Howard Hughes Medical Institute’s Janelia Research Campus, has reported a strategy for coaxing gut microbes to produce higher levels of colanic acid, a bacterial product that has been linked in prior work to longer life in animal models. (sciencedaily.com)
The study, published in PLOS Biology on November 11, 2025, found that exposing certain Escherichia coli strains to a low dose of the antibiotic cephaloridine led the bacteria to overproduce colanic acids. In the roundworm Caenorhabditis elegans, animals given cephaloridine lived longer, which the researchers linked to the increase in colanic acid. (sciencedaily.com)
The team also tested the approach in mice. According to the study’s summary and the journal report, oral low-dose cephaloridine triggered gene expression in gut bacteria tied to colanic acid biosynthesis and was associated with what the researchers described as an attenuation of age-related metabolic changes. The reported shifts included higher “good” cholesterol and lower “bad” cholesterol in male mice and reduced insulin levels in female mice. (sciencedaily.com)
A key premise of the approach is that cephaloridine can influence the gut microbiome without widespread effects in the rest of the body when administered orally. The researchers and the institutional summary describe cephaloridine as not being absorbed into the bloodstream when taken by mouth, which they argue could limit toxicity and other systemic side effects seen with many drugs. (sciencedaily.com)
In the paper, the authors report that the colanic-acid induction occurred through a mechanism that is independent of cephaloridine’s known antibiotic activity and involves the membrane-bound histidine kinase ZraS, suggesting the drug can act as a chemical signal to shift bacterial metabolism. (dx.doi.org)
The work was supported by the Howard Hughes Medical Institute, and the authors disclose that a patent application has been filed related to the research. (dx.doi.org)
