Impact of HIV and Type 2 diabetes on Gut Microbiota Diversity, Tryptophan Catabolism and Endothelial Dysfunction

Hedda Hoel, Malene Hove-Skovsgaard, Johannes R Hov, Julie Christine Gaardbo, Kristian Holm, Martin Kummen, Knut Rudi, Felix Nwosu, Jørgen Valeur, Marco Gelpi, Ingebjørg Seljeflot, Per Magne Ueland, Jan Gerstoft, Henrik Ullum, Pål Aukrust, Susanne Dam Nielsen, Marius Trøseid

31 Citations (Scopus)

Abstract

HIV infection and type 2 diabetes are associated with altered gut microbiota, chronic inflammation, and increased cardiovascular risk. We aimed to investigate the combined effect of these diseases on gut microbiota composition and related metabolites, and a potential relation to endothelial dysfunction in individuals with HIV-infection only (n = 23), diabetes only (n = 16) or both conditions (n = 21), as well as controls (n = 24). Fecal microbiota was analyzed by Illumina sequencing of the 16 S rRNA gene. Markers of endothelial dysfunction (asymmetric dimethylarginine [ADMA]), tryptophan catabolism (kynurenine/tryptophan [KT]-ratio), and inflammation (neopterin) were measured by liquid chromatography-tandem mass spectrometry. The combination of HIV and type 2 diabetes was associated with reduced gut microbiota diversity, increased plasma KT-ratio and neopterin. Microbial genes related to tryptophan metabolism correlated with KT-ratio and low alpha diversity, in particular in HIV-infected with T2D. In multivariate analyses, KT-ratio associated with ADMA (β = 4.58 [95% CI 2.53-6.63], p < 0.001), whereas microbiota composition per se was not associated with endothelial dysfunction. Our results indicate that tryptophan catabolism may be related to endothelial dysfunction, with a potentially detrimental interaction between HIV and diabetes. The potential contribution of gut microbiota and the impact for cardiovascular risk should be further explored in prospective studies powered for clinical end points.

Original languageEnglish
JournalScientific Reports
Volume8
Issue number1
Pages (from-to)6725
ISSN2045-2322
DOIs
Publication statusPublished - 30 Apr 2018

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