Duodenal microbiome differences may raise CVD risk in postmenopausal women not on HT
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Postmenopausal women taking hormone therapy have a duodenal microbiome similar to younger women and a lower abundance of taxa associated with cardiovascular disease risk compared with those not taking HT, researchers reported.
In an analysis of data from participants in the Revealing the Entire Intestinal Microbiota and its Associations with the Genetic, Immunologic, and Neuroendocrine Ecosystem (REIMAGINE) study, postmenopausal women not taking HT had decreased duodenal microbial diversity compared with postmenopausal women taking HT and reproductive-age women not taking exogenous hormones. The decreased microbial diversity was associated with lower total testosterone and higher fasting glucose in women not taking HT.
“This is the first study to examine changes in the duodenal microbiome in postmenopausal women, and the potential impacts of HT,” Ruchi Mathur, MD, FRCPC, director of clinical research, medically associate science and technology, and professor of medicine at Cedars-Sinai, told Healio. “Our results show that postmenopausal women not taking HT exhibit a significantly different core microbiome characterized by lower relative abundance of phylum Bacteroidetes, which was associated with decreased microbial diversity, increased fasting glucose levels and decreased testosterone levels. Postmenopausal women not taking HT also exhibit increased relative abundance of taxa from phylum Proteobacteria, which results in increased duodenal microbial dysbiosis, and increased relative abundance of taxa previously associated with increased risks for CVD.”
Mathur and colleagues analyzed data from 35 women undergoing esophagogastroduodenoscopy in the REIMAGINE study. The study cohort included postmenopausal women taking HT (n = 13; mean age, 61 years), postmenopausal women not taking HT (n = 12; mean age, 61 years) and women of reproductive age not taking exogenous hormones (n = 10; mean age, 32 years). Cholesterol, triglycerides, glucose, total protein and hormone levels were routinely collected. Microbial DNA was isolated from duodenal aspirates collected during upper endoscopy. Specific primers containing sequencing adapters (Illumina) were used to amplify the 16S V3 and V4 regions for ribosomal RNA sequencing.
The findings were published in Menopause
Duodenal microbial diversity linked to testosterone, glucose
Postmenopausal women not taking HT had lower levels of estradiol and progesterone compared with postmenopausal women taking HT and women of reproductive age. Total testosterone levels were lower (P = .02) and fasting glucose was higher (P = .014) in postmenopausal women not on HT compared with reproductive-age women, but there were no significant differences compared with postmenopausal women on HT.
Researchers used the Shannon, Simpson and Observed indices to analyze duodenal microbial alpha diversity. Postmenopausal women not on HT had decreased duodenal microbial diversity compared with those on HT and reproductive-age women for the Shannon index (P = .03). Postmenopausal women on HT had duodenal microbial diversity similar to reproductive-age women.
Lower duodenal microbial diversity was associated with decreased testosterone in postmenopausal women not on HT (Spearman rank correlation = –0.373; P = .05). Lower testosterone was associated with increased fasting glucose levels for postmenopausal women (Spearman rank correlation = –0.486; P = .035). A lower relative abundance of the phylum Bacteroidetes in the duodenal microbiome of postmenopausal women was associated with higher fasting glucose (Spearman rank correlation = –0.436; P = .048), lower duodenal microbial diversity (Spearman rank correlation = 0.697; P < .0001) and lower testosterone levels (Spearman rank correlation = 0.481; P = .02)
Duodenal microbiome diversity and CVD risk
Postmenopausal women not on HT had a greater duodenal abundance of Escherichia and Klebsiella from the phylum Proteobacteria, and Lactobacillus from the phylum Firmicutes compared with postmenopausal women on HT. This difference may possibly influence CVD risks in postmenopausal women.
“The duodenal microbiome in postmenopausal women taking HT is far more similar to that of reproductive-age women, with increased relative abundance of phylum Bacteroidetes and genus Prevotella, both of which are associated with decreased CVD risks,” Mathur said.
The researchers noted that a larger study with an analyses of CVD markers is needed to investigate how microbial metabolic pathways may affect CVD risk.
“While these results are very interesting, they do not prove a definitive causality,” Mathur said. “This work is still needed. In addition, identifying down to the species and strain levels could allow for potential interventions.”
For more information:
Ruchi Mathur, MD, FRCPC, can be reached at ruchi.mathur@cshs.org.
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