Gender differences in the bile acid profiles of APP/PS1 transgenic AD mice

Alzheimer's disease (AD) is a neurodegenerative disease and presents in the accumulation of amyloid and neurofibrillary tangle. The association between modulations of gut symbiotic microbes with neurological disease via bidirectional gut-brain axis has been well documented. Bile acid (BA) pools in the enterohepatic circulation could be valuable for probing complex biochemical interactions between host and their symbiotic microbiota. Herein we investigated the levels of 28 BAs in several compartments in enterohepatic circulation (including jejunal, ileum, cecum, colon and feces, plasma and liver tissue) by employing an APP/PS1 induced transgenic AD mouse model. We found that BA profiles in AD mice were gender specific. We observed decreased levels of taurine-conjugated primary BAs (TUDCA, TCA, T-α-MCA and T-β-MCA) and increased levels of secondary BA (iso-DCA) in plasma and liver extracts for female AD transgenic mice. In contrast, increased levels of TDCA in liver extracts and decreased levels of T-β-MCA in jejunal content were noted in male AD mice. These observations suggested that perturbations of BA profiles in AD mice displayed clear gender variations. Our study highlighted the roles of gut microbiota on neurodegenerative disease, which could be gender specific.