MON-188 - Sexual Dimorphism in Gut Microbes during Aging Coincide with Increased Circulating Bile Acids in Males Not Females.

Bile acids (BA) are cholesterol metabolites which are produced in the liver and transit into the small intestine during a meal, where gut microbes transform them before returning to liver via the portal vein. We recently published how sex differences in microbial compositions altered specifically the portal bile acids that recirculated back from the intestine in adult WT mice. Here, we present data that upon aging, 12-months-old WT male mice (n=7) show alterations in systemic bile acids, specifically those that are generated from 12-OH BA pool. This alteration was not seen in the WT females. Further analysis showed that taurine-conjugation increased while oxidation of BA was reduced in male portal blood. Such modifications are normally mediated by Bifidobacterium and Feacalibaculum that are present abundantly in male distal small intestine. On the other hand, there is no increase in 12-OH BAs in females (n=6). We identified high proportions of Turicibacter all along the gut in aged females, which is a member of the estrobolome (i.e., bacteria metabolizing estrogen) able to deconjugate taurocholic acid. To test if estrogen had a role in this process, we injected estradiol (n=4) and within 30 min we observed a rapid and significant decrease in 12-OH BA pool. Conversely, this pool increased in ovariectomized females (n=4). Altogether, these new data uncover how sex differences in gut microbes and estrogen may lower 12-OH BA pool in females compared to aged males.

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