Circulating Short-Chain Fatty Acids: Association with Vaginal Microbiota, Genital Inflammation, and HIV Acquisition

Little is known about the relationships between circulating short-chain fatty acids (SCFAs) and genital microbiota, inflammation, and the risk for HIV infection in women. As circulating SCFAs are potentially modifiable, for example, through dietary fiber or probiotics, we investigated association of circulating SCFA levels with these outcomes. We carried out a nested matched case-control study within a randomized trial of an antiretroviral microbicide to prevent HIV infection to study the association between circulating SCFAs and HIV acquisition (primary outcome for case definition), vaginal microbiota, and genital inflammation. Levels of the SCFAs butyrate, acetate, and propionate were quantified in plasma using mass spectrometry. Vaginal microbiota was assessed using metaproteomics and characterized as Lactobacillus dominant (LD) or low Lactobacillus (LL). Genital inflammation was measured using multiplex immunoassays. Logistic regression models were used to study the association of SCFAs with each outcome. Study population (N = 99) characteristics were similar between cases (33 who acquired HIV) and controls (66 who did not acquire HIV). We did not observe any associations between any of the circulating SCFAs with HIV acquisition or with LL vaginal microbiota status. However, there was an inverse association between circulating SCFAs and several pro-inflammatory genital cytokines, including interleukin-6 (IL-6), IL-1α, and IL-8. In our study of women with high risk of HIV infection, higher levels of circulating SCFAs were associated with lower levels of various genital inflammatory markers, but not with HIV acquisition or a LL microbiota profile. Future larger studies, including genital SCFA assessment, are needed to confirm these findings.