Host microbiota modulates development of social preference in mice

BACKGROUND Mounting evidence indicates that the indigenous gut microbiota exerts long-lasting programming effects on brain function and behaviour. OBJECTIVE In this study, we used the germ-free (GF) mouse model, devoid of any microbiota throughout development, to assess the influence of the indigenous microbiota on social preference and repetitive behaviours (e.g. self-grooming). METHODS AND RESULTS Using the three-chambered social approach task, we demonstrate that when adult GF mice were given a choice to spend time with a novel mouse or object, they spent significantly more time sniffing and interacting with the stimulus mouse compared to conventionally raised mice (specific pathogen-free, SPF). Time spent in repetitive self-grooming behaviour, however, did not differ between GF and SPF mice. Real-time PCR-based gene expression analysis of the amygdala, a key region that is part of the social brain network, revealed a significant reduction in the mRNA levels of total brain-derived neurotrophic factor (BDNF), BDNF exon I-, IV-, VI-, IX-containing transcripts, and NGFI-A (a signalling molecule downstream of BDNF) in GF mice compared to SPF mice. CONCLUSION These results suggest that differential regulation of BDNF exon transcripts in the amygdala by the indigenous microbes may contribute to the altered social development of GF mice.