Gut Biogeography Accentuates Sex-Related Differences in the Murine Microbiome

Recent studies have highlighted the influence of factors such as sex and sex-linked hormones on microbiome composition, raising concerns about the generalizability of findings. Here, we explore whether gut geography, specifically the upper and lower gastrointestinal tract (GI), contributes to sex-linked microbiome differences in mice. We collected microbial samples throughout the length of the GI from male and female C57B6/J mice at 6- and 8-weeks old, and conducted 16S rRNA sequencing. Our findings revealed significant sex-related differences, with Clostridium_sensu_stricto_1 more abundant in the male colon, while females exhibited higher levels of Dubosiella newyorkensis across all organs at 6 weeks. We also observed decreased Shannon alpha diversity in the small intestine compared to the lower GI, and this diversity decreased further at 8 weeks. Interestingly, our results suggest that age mitigates sex-related, but not gut geography-related differences in beta diversity, with implications for experimental outcomes and treatment strategies. This study underscores the dynamic nature of microbial diversity, influenced by sex, age, and GI localization, emphasizing the need for a more comprehensive understanding of microbiome dynamics in experimental research and clinical interventions.