Menopause Factors and Alterations in Gut Microbiota and Insulin Homeostasis: A Cross-Sectional Analysis of the Microbiome and Insulin Longitudinal Evaluation Study (Miles)

Authors

• Vincent J Maffei
• Alain G Bertoni
• Alexis C Wood
• Jerome I Rotter
• Osa Crago
• Yii-Der I Chen
• Joseph F Petrosino
• Kristi L Hoffman
• Mark O Goodarzi
• Elizabeth T Jensen

Language

English

Publication Date

10-1-2025

Journal

Diabetes, Obesity and Metabolism

DOI

10.1111/dom.16578

PMID

40735808

PMCID

PMC12715721

PubMedCentral® Posted Date

7-30-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Aim: To assess the risk for impaired insulin homeostasis as a function of menopause-related factors and gut microbiota dysbiosis in non-diabetic, post-menopausal women.

Materials and methods: Baseline data (n = 175 women) from the Microbiome and Insulin Longitudinal Evaluation Study (MILES) were used, including insulin and dysglycaemia indices calculated from a 2-h oral glucose tolerance test, untargeted peripheral metabolomics, targeted peripheral short chain fatty-acid levels and faecal bacterial microbiota surveyed by whole-metagenomic sequencing.

Results: After adjustment for covariates, menopause age < 50 years and use of hormone replacement therapy (HRT) were associated with lower Matsuda et al. insulin sensitivity index levels (β = -0.232, confidence interval (CI) = [-0.450, -0.014] and β = -0.275, CI = [-0.444, -0.107], respectively) but not pre-menopausal gynaecologic surgery. Pre-menopausal gynaecologic surgery was significantly associated with faecal microbiota beta diversity driven by a relative increase in diabetogenic Ruminococcus gnavus and Clostridium species and a decrease in protective Alistipes species and Akkermansia muciniphila relative abundances. A reduction in two glycerophospholipids in the plasmalogen class significantly statistically mediated an inverse association between gynaecologic surgery before menopause and insulin sensitivity.

Conclusions: Menopause age and history of HRT are more strongly associated with insulin resistance than gynaecologic surgery before menopause. However, gynaecologic surgery is associated with shifts in gut microbial composition and plasma metabolite levels with a potential to contribute to future diabetes risk.

Keywords

Humans, Female, Middle Aged, Gastrointestinal Microbiome, Longitudinal Studies, Cross-Sectional Studies, Insulin Resistance, Menopause, Homeostasis, Insulin, Dysbiosis, Adult, Feces, Glucose Tolerance Test, beta cell function, cohort study, insulin resistance, type 2 diabetes

Published Open-Access

yes

Recommended Citation

Maffei, Vincent J; Bertoni, Alain G; Wood, Alexis C; et al., "Menopause Factors and Alterations in Gut Microbiota and Insulin Homeostasis: A Cross-Sectional Analysis of the Microbiome and Insulin Longitudinal Evaluation Study (Miles)" (2025). Children’s Nutrition Research Center Staff Publications. 435.
https://digitalcommons.library.tmc.edu/staff_pub/435