Microbiota-derived butyrate dynamically regulates intestinal homeostasis through regulation of actin-associated protein synaptopodin

著者: Ruth X. Wang, J. Scott Lee, Eric L. Campbell, Sean P. Colgan - Proceedings of the National Academy of Sciences, PNAS 2020 被引用: 319

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.