Shieh · JCI insight 2020 · Longitudinal cohort study · n=65

Gut permeability, inflammation, and bone density across the menopause transition.

Cited 93 times in the scientific literature.

Level 3 - non-randomized controlled study

Longitudinal cohort study with repeated within-subject measures across menopause stages

PubMed 31830000 · doi:10.1172/jci.insight.134092 · record verified 2026-08-27

What was done

Researchers studied 65 women from the Study of Women's Health Across the Nation (SWAN) tracked from premenopause to postmenopause. They measured serum markers of gut barrier dysfunction (fatty acid binding protein 2 [FABP2]), microbial translocation (lipopolysaccharide-binding protein [LBP], soluble CD14 [sCD14]), systemic inflammation (high-sensitivity CRP), and bone mineral density (BMD) at the lumbar spine (LS) and total hip (TH). Repeated measures, mixed-effects linear regression models adjusted for BMI, premenopausal age, race/ethnicity, and study site were used to evaluate associations.

What was found

From premenopause to postmenopause, FABP2 increased by 22.8% (P = 0.001), LBP increased by 3.7% (P = 0.05), and sCD14 increased by 8.9% (P = 0.0002). In adjusted exploratory mixed-effects models, higher gut permeability was statistically associated with higher inflammation and lower LS and TH BMD (exact effect sizes, beta coefficients, and confidence intervals for these associations were not provided in the abstract).

Why it matters

This study provides clinical evidence in humans that the menopause transition involves increased intestinal permeability and microbial translocation, offering a biological link between estrogen loss, systemic inflammation, and postmenopausal bone loss.

Limits

The sample size is small (n = 65). Gut permeability was assessed indirectly through circulating biomarkers rather than direct functional probe testing (such as lactulose/mannitol excretion assays). Exact regression effect sizes and confidence intervals for the bone and inflammation associations were omitted from the abstract, and the observational design cannot establish causality.

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