Gut microbiota shapes social dominance through modulating HDAC2 in the medial prefrontal cortex

Abstract

Social dominance is a ubiquitous phenomenon among social animals, including humans. To date, individual attributes leading to dominance (after a contest) remain largely elusive. Here, we report that socially dominant rats can be distinguished from subordinates based on their intestinal microbiota. When dysbiosis is induced, rats are predisposed to a subordinate state, while dysbiotic rats reclaim social dominance following microbiota transplantation. Winning hosts are characterized by core microbes, a majority of which are associated with butyrate production, and the sole colonization of Clostridium butyricum is sufficient to restore dominance. Regarding molecular aspects, a histone deacetylase, HDAC2, is responsive to microbial status and mediates competition outcome; however, this occurs only in a restricted population of cells in the medial prefrontal cortex (mPFC). Furthermore, HDAC2 acts by modulating synaptic activity in mPFC. Together, these findings uncover a link between commensals and host dominance, providing insight into the gut-brain mechanisms underlying dominance determination.

Keywords: HDAC2; gut microbiota; medial prefrontal cortex; social dominance; sodium butyrate.