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

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...

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Autores principales: 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
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Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/eddc42361c83490db0116a19884a4ca5
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spelling oai:doaj.org-article:eddc42361c83490db0116a19884a4ca52021-12-02T16:08:01ZImpact of HIV and Type 2 diabetes on Gut Microbiota Diversity, Tryptophan Catabolism and Endothelial Dysfunction10.1038/s41598-018-25168-32045-2322https://doaj.org/article/eddc42361c83490db0116a19884a4ca52018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25168-3https://doaj.org/toc/2045-2322Abstract 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.Hedda HoelMalene Hove-SkovsgaardJohannes R. HovJulie Christine GaardboKristian HolmMartin KummenKnut RudiFelix NwosuJørgen ValeurMarco GelpiIngebjørg SeljeflotPer Magne UelandJan GerstoftHenrik UllumPål AukrustSusanne Dam NielsenMarius TrøseidNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
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
Impact of HIV and Type 2 diabetes on Gut Microbiota Diversity, Tryptophan Catabolism and Endothelial Dysfunction
description 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.
format article
author 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
author_facet 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
author_sort Hedda Hoel
title Impact of HIV and Type 2 diabetes on Gut Microbiota Diversity, Tryptophan Catabolism and Endothelial Dysfunction
title_short Impact of HIV and Type 2 diabetes on Gut Microbiota Diversity, Tryptophan Catabolism and Endothelial Dysfunction
title_full Impact of HIV and Type 2 diabetes on Gut Microbiota Diversity, Tryptophan Catabolism and Endothelial Dysfunction
title_fullStr Impact of HIV and Type 2 diabetes on Gut Microbiota Diversity, Tryptophan Catabolism and Endothelial Dysfunction
title_full_unstemmed Impact of HIV and Type 2 diabetes on Gut Microbiota Diversity, Tryptophan Catabolism and Endothelial Dysfunction
title_sort impact of hiv and type 2 diabetes on gut microbiota diversity, tryptophan catabolism and endothelial dysfunction
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/eddc42361c83490db0116a19884a4ca5
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