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Gut permeability, inflammation, and bone density across the menopause transition
Albert Shieh, … , Arun S. Karlamangla, Gail A. Greendale
Albert Shieh, … , Arun S. Karlamangla, Gail A. Greendale
Published December 12, 2019
Citation Information: JCI Insight. 2020;5(2):e134092. https://doi.org/10.1172/jci.insight.134092.
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Clinical Medicine Bone biology Endocrinology

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

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Abstract

BACKGROUND Inflammation is implicated in many aging-related disorders. In animal models, menopause leads to increased gut permeability and inflammation. Our primary objective was to determine if gut permeability increases during the menopause transition (MT) in women. Our exploratory objectives were to examine whether greater gut permeability is associated with more inflammation and lower bone mineral density (BMD).METHODS We included 65 women from the Study of Women’s Health Across the Nation (SWAN). Key measures were markers of gut permeability (gut barrier dysfunction, fatty acid binding protein 2 [FABP2]) and immune activation secondary to gut microbial translocation (LPS binding protein [LBP], soluble CD14 [sCD14]), inflammation (high-sensitivity CRP), and lumbar spine (LS) or total hip (TH) BMD.RESULTS In our primary analysis, FABP2, LBP, and sCD14 increased by 22.8% (P = 0.001), 3.7% (P = 0.05), and 8.9% (P = 0.0002), respectively, from pre- to postmenopause. In exploratory, repeated measures, mixed-effects linear regression (adjusted for BMI, age at the premenopausal visit, race/ethnicity, and study site), greater gut permeability was associated with greater inflammation, along with lower LS and TH BMD.CONCLUSION Gut permeability increases during the MT. Greater gut permeability is associated with more inflammation and lower BMD. Future studies should examine the longitudinal associations of gut permeability, inflammation, and BMD.FUNDING Funding for this research was provided by NIH, Department of Health and Human Services, through the National Institute on Aging, National Institute of Nursing Research, and NIH Office of Research on Women’s Health (U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, and U01AG012495).

Authors

Albert Shieh, Marta Epeldegui, Arun S. Karlamangla, Gail A. Greendale

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Figure 1

Scatter plots of gut permeability markers versus hs-CRP.

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Scatter plots of gut permeability markers versus hs-CRP.
(A–C) Plots of ...
(A–C) Plots of paired measures of FABP2 (A) (gut barrier dysfunction marker), LBP (B) (immune activation/gut microbial translocation marker), or sCD14 (C) (immune activation/gut microbial translocation marker) versus hs-CRP. Paired measures were obtained before menopause (closed circles, 3–5 years before the final menstrual period) and after menopause (open circles, 3–5 years after the final menstrual period). Vertical dashed lines indicate the median gut permeability marker values, and horizontal dashed lines mark the median hs-CRP value. A total of 65 subjects were included.

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