Marco Gelpi1, Beate Vestad2,3, Simen Hyll Hansen2,3,4, Kristian Holm2,3,4, Ninna Drivsholm1, Alexandra Goetz3,4, Nicolai Søren Kirkby5, Birgitte Lindegaard6,7, Anne-Mette Lebech8, Hedda Hoel2,3,9, Annika E Michelsen2,3, Thor Ueland2,3, Jan Gerstoft1, Jens Lundgren1,10, Johannes Roksund Hov2,3,4,11, Susanne Dam Nielsen1, Marius Trøseid2,3,12. 1. Viro-immunology Research Unit, Department of Infectious Diseases 8632, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 2. Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 3. Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway. 4. Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway. 5. Department of Microbiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 6. Center for inflammation and Metabolism, Rigshospitalet, København, Denmark. 7. Department of Pulmonary and Infectious Diseases, Nordsjællands Hospital, Hillerød, Denmark. 8. Department of Infectious Diseases, Hvidovre Hospital, Copenhagen University Hospital, Copenhagen, Denmark. 9. Medical Department, Lovisenberg Hospital, Oslo, Norway. 10. Centre of Excellence for Health, Immunity and Infections, Department of Infectious Diseases 8632, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 11. Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway. 12. Section of Clinical Immunology and Infectious Diseases, Department of Rheumatology, Dermatology and Infectious Diseases, Oslo, Norway.
Abstract
BACKGROUND: We aimed to identify a human immunodeficiency virus (HIV)-related microbiota signature, independent of sexual preferences and demographic confounders, in order to assess a possible impact of the microbiome on metabolic comorbid conditions. METHODS: Bacterial 16S ribosomal RNA analyses were performed on stool samples from 405 HIV-infected and 111 uninfected participants of the Copenhagen Comorbidity in HIV Infection (COCOMO) study. Individuals were stratified according to sexual behavior (men who have sex with men [MSM] vs non-MSM). RESULTS: After excluding MSM-associated microbiota traits and adjusting for confounders, we identified an HIV-related microbiota signature, consisting of lower biodiversity, increased relative abundance of the bacterial clades Gammaproteobacteria and Desulfovibrionaceae and decrease in several Clostridia. This microbiota profile was associated with a 2-fold excess risk of metabolic syndrome, driven by increase in Desulfovibrionaceae and decrease in Clostridia (Butyrivibrio, Coprococcus 2, Lachnospiraceae UCG-001 and CAG-56). This association was accentuated (5-fold excess risk) in individuals with previous severe immunodeficiency, which also modified the association between HIV-related microbiota signature and visceral adipose tissue (VAT) area (P for interaction = .01). Accordingly, HIV-related microbiota was associated with 30-cm2 larger VAT in individuals with history of severe immunodeficiency, but not in those without. CONCLUSION: The HIV-related microbiota was associated with increased risk of metabolic syndrome and VAT accumulation, particularly in individuals with previous severe immunodeficiency, driven by increased Desulfovibrionaceae and lower abundance of several Clostridia. Our findings suggest a potential interplay between HIV-related microbiota, immune dysfunction and metabolic comorbid conditions. Interventions targeting the gut microbiome may be warranted to reduce cardiovascular risk, particularly in individuals with previous immunodeficiency.
BACKGROUND: We aimed to identify a human immunodeficiency virus (HIV)-related microbiota signature, independent of sexual preferences and demographic confounders, in order to assess a possible impact of the microbiome on metabolic comorbid conditions. METHODS: Bacterial 16S ribosomal RNA analyses were performed on stool samples from 405 HIV-infected and 111 uninfected participants of the Copenhagen Comorbidity in HIV Infection (COCOMO) study. Individuals were stratified according to sexual behavior (men who have sex with men [MSM] vs non-MSM). RESULTS: After excluding MSM-associated microbiota traits and adjusting for confounders, we identified an HIV-related microbiota signature, consisting of lower biodiversity, increased relative abundance of the bacterial clades Gammaproteobacteria and Desulfovibrionaceae and decrease in several Clostridia. This microbiota profile was associated with a 2-fold excess risk of metabolic syndrome, driven by increase in Desulfovibrionaceae and decrease in Clostridia (Butyrivibrio, Coprococcus 2, Lachnospiraceae UCG-001 and CAG-56). This association was accentuated (5-fold excess risk) in individuals with previous severe immunodeficiency, which also modified the association between HIV-related microbiota signature and visceral adipose tissue (VAT) area (P for interaction = .01). Accordingly, HIV-related microbiota was associated with 30-cm2 larger VAT in individuals with history of severe immunodeficiency, but not in those without. CONCLUSION: The HIV-related microbiota was associated with increased risk of metabolic syndrome and VAT accumulation, particularly in individuals with previous severe immunodeficiency, driven by increased Desulfovibrionaceae and lower abundance of several Clostridia. Our findings suggest a potential interplay between HIV-related microbiota, immune dysfunction and metabolic comorbid conditions. Interventions targeting the gut microbiome may be warranted to reduce cardiovascular risk, particularly in individuals with previous immunodeficiency.
Authors: Scott Sherrill-Mix; Michelle Yang; Grace M Aldrovandi; Jason M Brenchley; Frederic D Bushman; Ronald G Collman; Satya Dandekar; Nichole R Klatt; Laurel A Lagenaur; Alan L Landay; Roger Paredes; Gilda Tachedjian; Jim A Turpin; Sergio Serrano-Villar; Catherine A Lozupone; Mimi Ghosh Journal: AIDS Res Hum Retroviruses Date: 2022-01-25 Impact factor: 2.205
Authors: Stéphane Isnard; John Lin; Brandon Fombuena; Jing Ouyang; Thibault V Varin; Corentin Richard; André Marette; Rayoun Ramendra; Delphine Planas; Laurence Raymond Marchand; Meriem Messaoudene; Claude P Van der Ley; Ido P Kema; Darakhshan Sohail Ahmed; Yonglong Zhang; Malcolm Finkelman; Bertrand Routy; Jonathan Angel; Petronela Ancuta; Jean-Pierre Routy Journal: Open Forum Infect Dis Date: 2020-09-11 Impact factor: 3.835
Authors: Stephanie M Dillon; Mona H Abdo; Melissa P Wilson; Jay Liu; Catherine M Jankowski; Charles E Robertson; Yunus Tuncil; Bruce Hamaker; Daniel N Frank; Samantha MaWhinney; Cara C Wilson; Kristine M Erlandson Journal: AIDS Res Hum Retroviruses Date: 2021-04-30 Impact factor: 1.723
Authors: Sergio Serrano-Villar; Alba Talavera-Rodríguez; María José Gosalbes; Nadia Madrid; José A Pérez-Molina; Ryan J Elliott; Beatriz Navia; Val F Lanza; Alejandro Vallejo; Majdi Osman; Fernando Dronda; Shrish Budree; Javier Zamora; Carolina Gutiérrez; Mónica Manzano; María Jesús Vivancos; Raquel Ron; Javier Martínez-Sanz; Sabina Herrera; Uxua Ansa; Andrés Moya; Santiago Moreno Journal: Nat Commun Date: 2021-02-18 Impact factor: 14.919
Authors: Marco Gelpi; Flora Mikaeloff; Andreas D Knudsen; Rui Benfeitas; Shuba Krishnan; Sara Svenssson Akusjärvi; Julie Høgh; Daniel D Murray; Henrik Ullum; Ujjwal Neogi; Susanne D Nielsen Journal: Aging (Albany NY) Date: 2021-10-11 Impact factor: 5.682
Authors: Tuula A Nyman; Malene Hove-Skovsgaard; Beate Vestad; Maria Stensland; Hedda Hoel; Anne-Marie Siebke Trøseid; Trude Aspelin; Hans Christian D Aass; Maija Puhka; Johannes R Hov; Susanne Dam Nielsen; Reidun Øvstebø; Marius Trøseid Journal: Sci Rep Date: 2021-11-09 Impact factor: 4.379
Authors: Malin Holm Meyer-Myklestad; Asle Wilhelm Medhus; Kristina Berg Lorvik; Ingebjørg Seljeflot; Simen Hyll Hansen; Kristian Holm; Birgitte Stiksrud; Marius Trøseid; Johannes Roksund Hov; Dag Kvale; Anne Margarita Dyrhol-Riise; Martin Kummen; Dag Henrik Reikvam Journal: J Infect Dis Date: 2022-02-15 Impact factor: 5.226
Authors: Stephanie M Dillon; Kaylee L Mickens; Tezha A Thompson; Emily H Cooper; Sabrina Nesladek; Allison J Christians; Moriah Castleman; Kejun Guo; Cheyret Wood; Daniel N Frank; Katerina Kechris; Mario L Santiago; Cara C Wilson Journal: Gut Microbes Date: 2022 Jan-Dec
Authors: Abigail J S Armstrong; Kevin Quinn; Jennifer Fouquier; Sam X Li; Jennifer M Schneider; Nichole M Nusbacher; Katrina A Doenges; Suzanne Fiorillo; Tyson J Marden; Janine Higgins; Nichole Reisdorph; Thomas B Campbell; Brent E Palmer; Catherine A Lozupone Journal: mSystems Date: 2021-05-18 Impact factor: 6.496