Sex hormones, the stool microbiome, and subclinical atherosclerosis in women with and without HIV
Brandilyn A Peters, David B Hanna, Yi Wang, Kathleen M Weber, Elizabeth Topper, Allison A Appleton, Anjali Sharma, Howard N Hodis, Nanette Santoro, Chantal Guillemette, Patrick Caron, Rob Knight, Robert D Burk, Robert C Kaplan, Qibin Qi- Biochemistry (medical)
- Clinical Biochemistry
- Endocrinology
- Biochemistry
- Endocrinology, Diabetes and Metabolism
Abstract
Background
The cardio-protective roles of endogenous estrogens may be particularly important in women with HIV, who have reduced estrogen exposure and elevated cardiovascular disease risk. The gut microbiome metabolically interacts with sex hormones, but little is known regarding how such interplay may impact cardiovascular risk.
Methods
Among 197 post-menopausal women in the Women’s Interagency HIV Study, we measured 15 sex hormones in serum and assessed the gut microbiome in stool. B-mode ultrasound was used to determine presence of carotid artery plaque in a subset (n = 134). We examined associations of (1) sex hormones and stool microbiome, (2) sex hormones and plaque, and (3) sex hormone-related stool microbiota and plaque, adjusting for potential confounders.
Results
Participant median age was 58 years and the majority were living with HIV (81%). Sex hormones (estrogens, androgens, and adrenal precursors) were associated with stool microbiome diversity and specific species, similarly in women with and without HIV. For example, estrogens were associated with higher diversity, higher abundance of species from Alistipes, Collinsella, Erysipelotrichia, and Clostridia, and higher abundance of microbial β-glucuronidase and aryl-sulfatase orthologs, which are involved in hormone metabolism. Several hormones were associated with lower odds of carotid artery plaque, including dihydrotestosterone, 3α-diol-17G, estradiol, and estrone. Exploratory mediation analysis suggested that estrone-related species, particularly from Collinsella, may mediate the protective association of estrone with plaque.
Conclusion
Serum sex hormones are significant predictors of stool microbiome diversity and composition, likely due in part to metabolic interactions. The gut microbiome may play a role in estrogen-related cardiovascular protection.