Gut microbiota and plasma metabolites associated with diabetes in women with, or at high risk for, HIV infection

EBioMedicine. 2018 Nov:37:392-400. doi: 10.1016/j.ebiom.2018.10.037. Epub 2018 Oct 23.

Abstract

Background: Gut microbiota alteration has been implicated in HIV infection and metabolic disorders. The relationship between gut microbiota and diabetes has rarely been studied in HIV-infected individuals, who have excess risk of metabolic disorders.

Methods: Our study during 2015-2016 enrolled predominantly African Americans and Hispanics in the Women's Interagency HIV Study. We studied 28 women with long-standing HIV infection under antiretroviral therapy and 20 HIV-uninfected, but at high risk of infection, women (16 HIV+ and 6 HIV- with diabetes). Fecal samples were analyzed by sequencing prokaryotic16S rRNA gene. Plasma metabolomics profiling was performed by liquid chromatography-tandem mass spectrometry.

Findings: No significant differences in bacterial α- or β-diversity were observed by diabetes or HIV serostatus (all P > .1). Relative abundances of four genera (Finegoldia, Anaerococcus, Sneathia, and Adlercreutzia) were lower in women with diabetes compared to those without diabetes (all P < .01). In women with diabetes, plasma levels of several metabolites in tryptophan catabolism (e,g., kynurenine/tryptophan ratio), branched-chain amino acid and proline metabolism pathways were higher, while glycerophospholipids were lower (all P < .05). Results were generally consistent between HIV-infected and HIV-uninfected women, and no significant modification effects by HIV serostatus were observed (all Pinteraction > 0.05). Anaerococcus, known to produce butyrate which is involved in anti-inflammation and glucose metabolism, showed an inverse correlation with kynurenine/tryptophan ratio (r = -0.38, P < .01).

Interpretation: Among women with or at high risk for HIV infection, diabetes is associated with gut microbiota and plasma metabolite alteration, including depletion of butyrate-producing bacterial population along with higher tryptophan catabolism. FUND: NHLBI (K01HL129892, R01HL140976) and FMF.

Keywords: Diabetes; Gut microbiota; HIV; Metabolite.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Anti-Retroviral Agents / administration & dosage*
  • Bacteria* / classification
  • Bacteria* / metabolism
  • Biomarkers / blood
  • Diabetes Mellitus* / blood
  • Diabetes Mellitus* / drug therapy
  • Diabetes Mellitus* / microbiology
  • Female
  • Gastrointestinal Microbiome*
  • HIV Infections* / blood
  • HIV Infections* / drug therapy
  • HIV Infections* / epidemiology
  • HIV Infections* / microbiology
  • Humans
  • Middle Aged
  • Prospective Studies

Substances

  • Anti-Retroviral Agents
  • Biomarkers