BACKGROUNDInflammation 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).METHODSWe 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.RESULTSIn 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.CONCLUSIONGut 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.FUNDINGFunding 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).