Microbiota-derived butyrate dynamically regulates intestinal homeostasis through regulation of actin-associated protein synaptopodin
Ruth X. Wang, J. Scott Lee, Eric L. Campbell, Sean P. Colgan
Abstract
Significance Intestinal epithelial barrier dysfunction and dysbiosis are central themes of inflammatory bowel diseases (IBDs). Initial studies revealed that the SCFA butyrate selectively promotes epithelial wound-healing responses. Using unbiased single-cell RNA sequencing approaches, we identified a cluster of actin-associated genes regulated by butyrate. Among these, we showed the selective induction of SYNPO as an intestinal tight junction protein with a central role in epithelial barrier regulation. Studies in vivo revealed that microbiota depletion abolished SYNPO expression that was rescued with butyrate. Analysis of Synpo -deficient mice revealed increased susceptibility to colitis and delayed resolution of disease with increased mucosal permeability. These findings highlight a fundamental contribution of the microbiota to homeostatic intestinal mucosal function through selective regulation of SYNPO.