Gut reaction

In a study published in the Journal of Experimental Medicine in January, Ludwig Chicago Co-director Ralph Weichselbaum and Yang-Xin Fu of the University of Texas Southwestern Medical Center showed how certain gut bacteria can reduce the efficacy of radiotherapy. They identified two families of bugs—Lachnospiraceae and Ruminococcaceae—that interfere with radiotherapy in mice and described how the short-chain fatty acid butyrate, a metabolic byproduct of these bacteria, undermines the therapy. The antibiotic vancomycin decreased the abundance of butyrate-producing gut bacteria and enhanced antitumor responses following radiotherapy in mice. Previous studies led by Ralph and Yang-Xin have shown that radiation activates a signaling pathway in dendritic cells that primes other immune cells—killer T cells—to attack tumors. This pathway, controlled by a protein named STING, ramps up the dendritic cells’ production of immune-stimulating factors known as type-1 interferons (IFN-I), which boost T cell activation. In this study, they show that butyrate inhibits a step of the biochemical signaling cascade that links STING activation to the production of IFN-I. The researchers suggest that the highly selective targeting of butyrate-producing gut microbiota may augment the radiotherapy sensitivity of tumors and improve patient responses.

This article appeared in the April 2021 issue of Ludwig Link. Click here to download a PDF (1.4 MB).


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