Abstract: The gut microbiota produces a wide variety of metabolites, which interact with intestinal cells by modulating either gene transcription or post-translational modifications of gut proteins. The effect of gut commensal bacteria on SUMOylation, an essential ubiquitin-like modification in intestinal physiology, remains however unknown. Here, the inventors show that branched chain fatty acids (BCFAs) increase protein SUMOylation in different intestinal cell lines. They demonstrated that the hyperSUMOylation induced by BCFAs inhibits the activation of the NF-?B pathway by blocking the degradation of the inhibitory factor I?B? in response to TNF?. This results in a decrease in pro-inflammatory cytokines expression as well as a decrease in intestinal epithelial permeability in response to TNF?.