Sex-Specific Gut Microbiome Functions in Alzheimer’s Disease BXD Mice

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Abstract

Alzheimer's disease is a devastating neurodegenerative disorder, with growing evidence implicating the gut microbiome in its pathogenesis. This study investigated the sex-specific gut microbiome functions in Alzheimer's disease using the AD-BXD mouse model, which combines the 5xFAD transgene with genetically diverse BXD strains. The literature review highlights the growing evidence linking the gut microbiome to neurodegenerative processes and the potential role of sex differences in the gut microbiome in contributing to disparities in AD risk and pathology. The purpose of this study was to reveal sex-specific metabolic modules and their potential ties to neurodegeneration. Using an integrated iMGMC-based pipeline, shotgun metagenomes from ten AD-BXD mice (five male, five female) were analyzed to compare male and female gut microbial functions at the KO and pathway levels. The results showed overlapping functional profiles across sexes but identified 21 sex-biased KOs, with distinct patterns observed in metabolic, cancer-related, and sulfur-amino-acid pathways. This sex-split reconstruction framework provides insights into how male and female microbiomes might differentially influence neurodegeneration in AD-BXD models, which could inform future targeted therapies.

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