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

Jennifer A. Fulcher*, Fan Li, Nicole H. Tobin, Sara Zabih, Julie Elliott, Jesse L. Clark, Richard D'Aquila, Brian Mustanski, Michele D. Kipke, Steven Shoptaw, Pamina M. Gorbach, Grace M. Aldrovandi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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-α, 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).

Original languageEnglish (US)
Article number104286
JournalEBioMedicine
Volume84
DOIs
StatePublished - Oct 2022

Funding

We would like to thank all study participants for their generous participation in these studies. This work was supported in part by NIH/NIAID (K08 AI124979 to J.A.F; P30 AI117943 to R.D. and B.M), NIH/NIDA (U01 DA036267 to S.S. and P.M.G; U01 DA036939 to B.M; U01 DA036926 to M.D.K; U24 DA044554 to P.M.G), and NIH/NIMH (P30 MH058107 to S.S; R34 MH105272 to J.L.C). Additional support was provided by the UCLA AIDS Institute, the UCLA Center for AIDS Research (NIH/NIAID AI028697), and the UCLA Pediatric AIDS Coalition.

Keywords

  • Cytokines
  • HIV
  • HIV acquisition
  • Microbiome

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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