The trillions of beneficial commensal microorganisms that normally reside in the gastrointestinal tract have emerged as a critical source of environmentally-derived stimuli that can impact health and disease. However, the underlying cellular and molecular mechanisms that recognize commensal bacteria-derived signals and regulate mammalian homeostasis are just beginning to be defined. Highly coordinated epigenomic modifications allow mammals to alter the transcriptional program of a cell in response to environmental cues. These modifications may play a key role in regulating the dynamic relationship between mammals and their microbiota. We review recent advances in understanding the interplay between the microbiota and mammalian epigenomic pathways, and highlight emerging findings that implicate a central role for histone deacetylases (HDACs) in orchestrating host–microbiota interactions.
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