Abstract

Type 2 diabetes is a known risk factor for urinary tract infection and vulvovaginal candidiasis, and this risk is modulated in part by vaginal microbiota. We sought to assess the associations between diabetes and the vaginal microbiota, specifically whether diabetes may reduce vaginal Lactobacillus spp., which produce lactic acid and protect the urogenital tract. This study included 811 participants (2,301 person-visits) aged 35-60 recruited to a 2-year observational cohort with mid-vaginal sampling every 6 months. Diabetes was defined as self-reported diabetes medications, history, or serum glycated albumin (GA) levels >16.5% (HbA1c not available). Vaginal microbiota was characterized by 16S rRNA gene sequencing and clustered into community state types (CSTs) by VALENCIA, a nearest centroid algorithm based on a reference dataset. Mixed-effects multinomial logistic regression with bootstrapping was used to assess the association between case status and CSTs. Among diabetes cases (n=45, 130 person-visits), 45% had L. crispatus, L. jensenii, L. gasseri-dominated (CST I/II/V), 12% had L. iners-dominated (CST III) and 43% had low-Lactobacillus (CST IV) microbiota. Diabetes cases had reduced odds of L. iners-dominated CST III (aOR: 0.54, 95% CI: 0.31-0.81) than controls (12% vs 24%) and no association with low-Lactobacillus CST IV (aOR=01.05, 95% CI: 0.76-1.44) compared to Lactobacillus-dominated CST I/II/V in a model adjusted for menopause status and race. Estimates were similar when only GA was used for a diabetes case definition on a subset (1,001 person-visits). The results suggest diabetes is associated with reduced L. iners dominance. Diabetes cases had even frequencies of low-Lactobacillus or the optimal Lactobacillus-dominated CSTs. L. iners is metabolically distinct from other lactobacilli, producing only L-lactic acid (not the more protective D-lactic acid), and is associated with increased reproductive tract infection risk. This data informs how diabetes may affect the vaginal microenvironment. Disclosure S. J. Robbins: None. R. M. Brotman: None. R. S. Miller: None. A. L. Beitelshees: None. M. Shardell: None. J. Ravel: None. S. I. Taylor: Consultant; Ionis Pharmaceuticals. Funding National Institute of Allergy and Infectious Diseases (F31-AI164859)

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