Environmental cues shape mucosal enteric glia networks independent of lamina propria innervation

Abstract Mucosal enteric glia are implicated in different aspects of gut function but the determinants of their occupancy of the lamina propria remain obscure. Analyzing mucosal enteric glia during intestinal inflammation and in mouse models differing for diet and gut microbiota, we found that colitis drastically impacts glial network organization, and that diet modulates mucosal glia cyto-architecture, with microbiota inducing intestinal region-specific variations. Restored by conventionalization, germ-free mice exhibit reduced mucosal glia numbers throughout the intestine. Vagotomy affects mucosal enteric glia maintenance in a diet-dependent fashion but does not influence lamina propria colonization. Also, differences in nerve fiber density fail to account for the variations in mucosal enteric glia networks. Providing insight into their interaction with neuronal components and the luminal milieu, our results emphasize the profound plasticity of enteric glia, and suggest that their presence in the mucosa is not merely configured by lamina propria innervation.