Impact of the gut microbiota on enhancer accessibility in gut intraepithelial lymphocytes

The gut microbiota impacts many aspects of host biology including immune function. One hypothesis is that microbial communities induce epigenetic changes with accompanying alterations in chromatin accessibility, providing a mechanism that allows a community to have sustained host effects even in the face of its structural or functional variation. We used ATAC-seq to define chromatin accessibility in predicted enhancer regions of intestinal αβ+ and γδ+ intraepithelial lymphocytes (IELs) purified from germ-free mice, their conventionally-raised (CONV-R) counterparts, and mice reared GF and then colonized with a CONV-R gut microbiota at the end of the suckling-weaning transition. Characterizing genes adjacent to traditional enhancers and super-enhancers revealed signaling networks, metabolic pathways, and enhancer-associated transcription factors affected by the microbiota. Our results support the notion that epigenetic modifications help define microbial community-affiliated functional features of host immune cell lineages. We interrogated chromatin accessibility using ATAC-seq in four cell types derived from mice (CD4+ T cells, CD8+ T cells, αβ+ intraepithelial lymphocytes, and γδ+ intraepithelial lymphocytes), across three gut microbial colonization states (germ-free, conventionally-raised, and conventionalized).