Gut microbiota determines the social behavior of mice and induces metabolic and inflammatory changes in their adipose tissue

Abstract

The link between the gut microbiota and social behavior has been demonstrated, however the translational impact of a certain microbiota composition on stable behavioral patterns is yet to be elucidated. Here we employed an established social behavior mouse model of dominance (Dom) or submissiveness (Sub). A comprehensive 16S rRNA gene sequence analysis of Dom and Sub mice revealed a significantly different gut microbiota composition that clearly distinguishes between the two behavioral modes. Sub mice gut microbiota is significantly less diverse than that of Dom mice, and their taxa composition uniquely comprised the genera Mycoplasma and Anaeroplasma of the Tenericutes phylum, in addition to the Rikenellaceae and Clostridiaceae families. Conversely, the gut microbiota of Dom mice includes the genus Prevotella of the Bacteriodetes phylum, significantly less abundant in Sub mice. In addition, Sub mice show lower body weight from the age of 2 weeks and throughout their life span, accompanied with lower epididymis white adipose tissue (eWAT) mass and smaller adipocytes together with substantially elevated expression of inflammation and metabolic-related eWAT adipokines. Finally, fecal microbiota transplantation into germ-free mice show that Sub-transplanted mice acquired Sub microbiota and adopted their behavioral and physiological features, including depressive-like and anti-social behaviors alongside reduced eWAT mass, smaller adipocytes, and a Sub-like eWAT adipokine profile. Our findings demonstrate the critical role of the gut microbiome in determining dominance vs. submissiveness and suggest an association between gut microbiota, the eWAT metabolic and inflammatory profile, and the social behavior mode.

Isolated Grauer’s gorilla populations differ in diet and gut microbiome

“…Further, diet can reflect local adaptation, if populations specialise due to local availability of different foods or different foraging behaviours and cultures (Alberdi et al, 2020). Tightly linked to diet, the gut microbiome impacts long-term health and behaviour of its host, by aiding digestion, modulating dietary choice, and stimulating the immune system (Agranyoni et al, 2021;Colston & Jackson, 2016;Davidson et al, 2020;Ley et al, 2008;Moran et al, 2019). Isolated populations in different habitats have been shown to possess unique gut microbiomes, which is likely a result of ecological and genetic differences (Bueno de Mesquita et al, 2021;Couch et al, 2020;Fietz et al, 2018).…”

Stressor-Induced Reduction in Cognitive Behavior is Associated with Impaired Colonic Mucus Layer Integrity and is Dependent Upon the LPS-Binding Protein Receptor CD14

“… 91–93 Increased abundance in Rikenellaceae has also been observed in subordinate mice, and fecal transplants from subordinate mice into germ-free recipients can recapitulate many behaviors associated with subordination, including depressive-like behavior and social avoidance. 94 Thus, it was reasonable to test whether bacterial relative abundances were related to behavior. However, in our analyses, the relative abundance of specific bacterial types did not directly correlate with any behavioral differences.…”

Emerging roles for microglia and microbiota in the development of social circuits

“…Specifically, dominant and submissive male mice have significantly different gut microbiome compositions, with less diversity in submissive males as compared to dominant males. Fecal microbiota transplantation from dominant males into germ-free mice increased sociability, while microbiota transplanted from submissive males lead to reduced social behavior ( Agranyoni et al., 2021 ). Finally, germ-free mice colonized with microbiota from human patients with ASD display reduced sociability as compared to those colonized with microbiota from typically developing children ( Sharon et al., 2019 ).…”