Social stress causes gut dysbiosis in male, female, and aggressor mice

Abstract

BACKGROUNDPsychological stress causes gut dysbiosis, which is associated with adverse effects on physical and mental health in humans and mice. Understanding the specific taxa of gut bacteria changed by stress, and whether stress differentially alters their relative abundance in males and females, has important implications for stress-related disorders. METHODSWe modeled individual differences in resilience or susceptibility using the chronic social defeats stress (CSDS) paradigm. Here, C57BL/6 mice are exposed to a novel retired breeder CD-1 aggressor for 10 minutes per day for 10 days. In this paradigm, resilient and susceptible subpopulations can be identified using the social interaction paradigm following CSDS. Fecal samples were collected following Day 1 and Day 10 of CSDS. 16S ribosomal RNA sequencing was used to identify the relative abundance of 200 bacteria species. We analyzed group differences in phyla, genera, and species in CD-1 aggressors along with resilient, susceptible, and non-stressed control male and female C57/BL/6 intruders. RESULTSStress reduced microbiome diversity and caused gut dysbiosis in all groups, including aggressors. CSDS altered the relative abundance of every phylum detected. We report genera whose relative abundance was changed by CSDS or sex. Increases in the relative abundance of an uncultured Ruminococcus species on day 1 predicted aspects of social behavior, with a stronger correlation in stressed females compared to males. CONCLUSIONSCSDS causes gut dysbiosis in male and female mice, with generally similar effects in mice that behave differently following stress. ONE SENTENCE SUMMARYWe report the effects of chronic social defeat stress on gut dysbiosis in aggressors, non-defeated controls, and male and female mice that are either resilient or susceptible to the adverse effects of stress. IN THIS ISSUE SUMMARYWe characterize changes to the gut microbiome of male and female mice that are either resilient or susceptible to the adverse effects of social stress. Stress shifted the relative abundance of broad and specific taxa, which sometimes differed between males and females. We found that the abundance of an uncultured Ruminococcus species on day 1 predicted social behavior following stress. This effect was primarily observed in females.