Gut dysbiosis and inflammatory blood markers precede HIV with limited changes after early seroconversion

Background Alterations in the gut microbiome have been associated with HIV infection, but the relative impact of HIV versus other factors on the gut microbiome has been difficult to determine in cross-sectional studies.Methods To address this, we examined the gut microbiome, serum metabolome, and cytokines longitudinally within 27 individuals before and during acute HIV using samples collected from several ongoing cohort studies. Matched control participants (n=28) from the same cohort studies without HIV but at similar behavioral risk were used for comparison.Findings We identified few changes in the microbiome during acute HIV infection, but did find alterations in serum metabolites involving secondary bile acid (lithocholate sulfate, glycocholenate sulfate) and amino acid metabolism (3-methyl-2-oxovalerate, serine, cysteine, N-acetylputrescine). Greater microbiome differences, including decreased Bacteroides spp and increased Megasphaera elsdenii, were seen when comparing pre-HIV infection visits to matched at-risk controls. Those who acquired HIV also had elevated inflammatory cytokines (TNF-a, B cell activating factor, IL-8) and bioactive lipids (palmitoyl-sphingosine-phosphoethanolamide and glycerophosphoinositol) prior to HIV acquisition compared to matched controls.Interpretation Longitudinal sampling identified pre-existing microbiome differences in participants with acute HIV compared to matched control participants observed over the same period. These data highlight the importance of increasing understanding of the role of the microbiome in HIV susceptibility.Funding This work was supported by NIH/NIAID (K08AI124979; P30AI117943), NIH/NIDA (U01DA036267; U01DA036939; U01DA036926; U24DA044554), and NIH/NIMH (P30MH058107; R34MH105272).Copyright Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/) eBioMedicine ebiom.2022.104286