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
Affiliations
Jennifer A. Fulcher
Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA; Corresponding author at: Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, MacDonald Research Laboratories 4736, 675 Charles E Young Dr S, Los Angeles, CA 90095 USA.
Fan Li
Division of Infectious Diseases, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
Nicole H. Tobin
Division of Infectious Diseases, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
Sara Zabih
Division of Infectious Diseases, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
Julie Elliott
Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
Jesse L. Clark
Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
Richard D'Aquila
Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Brian Mustanski
Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Institute for Sexual and Gender Minority Health and Wellbeing, Northwestern University, Chicago, IL 60611, USA
Michele D. Kipke
Children's Hospital Los Angeles, Los Angeles, CA 90027, USA; Department of Pediatrics, Keck School of Medicine at the University of Southern California, Los Angeles, CA 90027, USA
Steven Shoptaw
Department of Family Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
Pamina M. Gorbach
Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA
Grace M. Aldrovandi
Division of Infectious Diseases, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
Summary: 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).
