Gut microbiota dysbiosis is a key pathological feature closely linked to metabolic disorders and neuroinflammation. It is typically characterized by reduced levels of beneficial microbial metabolites, particularly short-chain fatty acids (SCFAs) such as butyrate, and by increased production of pro-inflammatory molecules. In this study, we investigated the therapeutic potential of butyrate in a mouse model of antibiotic-induced gut dysbiosis, which is characterized by disruption of the normal gut microbiota and associated intestinal inflammation. We found that oral administration of sodium butyrate significantly reduced gut inflammation, as evidenced by decreased levels of the pro-inflammatory biomarkers calprotectin and lipocalin-2 in fecal samples compared with untreated dysbiotic mice. Furthermore, antibiotic treatment led to a marked reduction in specific butyrate-producing bacterial species, including Faecalibacterium prausnitzii and Roseburia spp. Notably, the abundance of these species, was partially restored following exogenous butyrate administration. Finally, butyrate administration significantly attenuated neuronal hyperexcitability in response to intracolonic distension and reduced pro-inflammatory factor levels in the spinal cord. These results highlight the role of butyrate in directly reducing gut inflammation and spinal neuroinflammation, while also promoting the restoration of some butyrate-producing bacteria. Our study underscores the potential of butyrate as a therapeutic agent for treating dysbiosis-associated gut inflammation and neuroinflammatory disorders, offering new insights into microbiota-targeted therapies for gut-brain axis regulation.
Fusco et al. (2026) studied this question.