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Gut permeability, inflammation, and bone density across the menopause transition
Albert Shieh, Marta Epeldegui, Arun S. Karlamangla, Gail A. Greendale
Albert Shieh, Marta Epeldegui, Arun S. Karlamangla, Gail A. Greendale
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Clinical Research and Public Health 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 3

Analysis sample derivation.

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Analysis sample derivation.
This flow chart shows the derivation of the ...
This flow chart shows the derivation of the analysis sample. In order to be included in the study, participants needed to meet the following criteria: (a) have undergone natural menopause; (b) have a known final menstrual period (FMP) date; (c) have at least 1 visit in premenopause and 1 visit in postmenopause from which previously collected plasma could be accessed through the SWAN Repository to measure FABP2, LBP, and sCD14; (d) have preexisting measures of E2, FSH, hs-CRP, and BMD corresponding to the plasma sample times; and (e) have not used sex steroid medications or bone-modifying agents in between their pre- and postmenopausal pilot study visits. A total of 621 women met these criteria. From this potential pool of subjects, the SWAN Repository randomly selected 65 women for this pilot study.

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