Tryptophan metabolism, gut microbiota, and carotid artery plaque in women with and without HIV infection

Abstract

AbstractBackgroundThe perturbation of tryptophan (TRP)-kynurenine (KYN) metabolism has been linked with HIV infection and cardiovascular disease (CVD), but the interrelationship among TRP metabolites, gut microbiota, and atherosclerosis has not yet been fully understood in the context of HIV infection.MethodsWe included 361 women (241 HIV+, 120 HIV-) with carotid artery plaque assessments from the Women’s Interagency HIV Study, measured ten plasma TRP metabolites and profiled fecal gut microbiome. TRP metabolites related gut microbial features were selected through the Analysis of Compositions of Microbiomes with Bias Correction method. The associations of TRP metabolites and related microbial features with plaque were examined using multivariable logistic regression.ResultsWhile plasma kynurenic acid (KYNA) (odds ratio [OR]=1.93[1.12, 3.32] per one SD increase,P=0.02) and KYNA/TRP (OR=1.83[1.08, 3.09],P=0.02) were positively associated with plaque, indole-3-propionate (IPA) (OR=0.62 [0.40, 0.98],P=0.03) and IPA/KYNA (OR=0.51[0.33, 0.80],P<0.01) were inversely associated with plaque. Five gut bacterial genera and many affiliated species were positively associated with IPA (FDR-q<0.25), includingRoseburia sp.,Eubacterium sp.,Lachnospira sp., andCoprobacter sp.; but no bacterial genera were found to be associated with KYNA. Furthermore, an IPA-associated-bacteria score was inversely associated with plaque (OR=0.47[0.28, 0.79],P<0.01). But no significant effect modification by HIV serostatus was observed in these associations.ConclusionsIn a cohort of women living with and without HIV infection, plasma IPA levels and related gut bacteria were inversely associated with carotid artery plaque, suggesting a potential beneficial role of IPA and its gut bacterial producers in atherosclerosis and CVD.