Microbiome-produced nicotinic acid controls colon regional identity and injury susceptibility

Regional structure of the intestinal epithelium is critical for its function and is associated with the risk of specific gut diseases. However, how regionalization is established and how it influences disease susceptibility remains poorly understood. Here, we investigated the role of the gut microbiome – which comprises all microorganisms residing in the gut lumen and is itself regionalized – in regulating regionalization of the colon. We found that the proximo-distal identity of colonocytes is disrupted in mice lacking a microbiome and that the proximal colonic microbiome produces high levels of nicotinic acid, which induces Pparα expression to establish proximal colonocyte identity. Furthermore, we report that microbiome-driven proximal identity confers protection against tissue injury in the mouse. Finally, we determined that colon regionalization and the loss of proximal identity during disease are also present in human colon samples.ate the study abstract/description