TY - JOUR
T1 - Impaired gut microbiota-mediated short-chain fatty acid production precedes morbidity and mortality in people with HIV
AU - Sereti, Irini
AU - Verburgh, Myrthe L.
AU - Gifford, Jacob
AU - Lo, Alice
AU - Boyd, Anders
AU - Verheij, Eveline
AU - Verhoeven, Aswin
AU - Wit, Ferdinand W.N.M.
AU - Schim van der Loeff, Maarten F.
AU - Giera, Martin
AU - Kootstra, Neeltje A.
AU - Reiss, Peter
AU - Vujkovic-Cvijin, Ivan
N1 - Funding Information: I.V.-C. was supported by the Crohn’s & Colitis Foundation , award number 831262, by the Karsh Family Foundation, and the Cedars-Sinai Digestive Diseases Research Center . This work was supported in part by The Netherlands Organization for Health Research and Development (ZonMW) (grant number 300020007 ) and Aids Fonds (grant number 2009063 ) and by the intramural research program of NIAID / NIH . We thank the AGE h IV cohort study group for establishing the cohort from which participants were selected. Additional unrestricted scientific grants were received from Gilead Sciences , ViiV Healthcare , Janssen Pharmaceuticals N.V. , and Merck & Co. None of these funding bodies had a role in the design or conduct of the study, the analysis or interpretation of the results, the writing of the report, or the decision to publish. Publisher Copyright: © 2023 The Authors
PY - 2023/11/28
Y1 - 2023/11/28
N2 - Antiretroviral therapy (ART) has dramatically lengthened lifespan among people with HIV (PWH), but this population experiences heightened rates of inflammation-related comorbidities. HIV-associated inflammation is linked with an altered microbiome; whether such alterations precede inflammation-related comorbidities or occur as their consequence remains unknown. We find that ART-treated PWH exhibit depletion of gut-resident bacteria that produce short-chain fatty acids (SCFAs)—crucial microbial metabolites with anti-inflammatory properties. Prior reports establish that fecal SCFA concentrations are not depleted in PWH. We find that gut-microbiota-mediated SCFA production capacity is better reflected in serum than in feces and that PWH exhibit reduced serum SCFA, which associates with inflammatory markers. Leveraging stool and serum samples collected prior to comorbidity onset, we find that HIV-specific microbiome alterations precede morbidity and mortality in ART-treated PWH. Among these microbiome alterations, reduced microbiome-mediated conversion of lactate to propionate precedes mortality in PWH. Thus, gut microbial fiber/lactate conversion to SCFAs may modulate HIV-associated comorbidity risk.
AB - Antiretroviral therapy (ART) has dramatically lengthened lifespan among people with HIV (PWH), but this population experiences heightened rates of inflammation-related comorbidities. HIV-associated inflammation is linked with an altered microbiome; whether such alterations precede inflammation-related comorbidities or occur as their consequence remains unknown. We find that ART-treated PWH exhibit depletion of gut-resident bacteria that produce short-chain fatty acids (SCFAs)—crucial microbial metabolites with anti-inflammatory properties. Prior reports establish that fecal SCFA concentrations are not depleted in PWH. We find that gut-microbiota-mediated SCFA production capacity is better reflected in serum than in feces and that PWH exhibit reduced serum SCFA, which associates with inflammatory markers. Leveraging stool and serum samples collected prior to comorbidity onset, we find that HIV-specific microbiome alterations precede morbidity and mortality in ART-treated PWH. Among these microbiome alterations, reduced microbiome-mediated conversion of lactate to propionate precedes mortality in PWH. Thus, gut microbial fiber/lactate conversion to SCFAs may modulate HIV-associated comorbidity risk.
KW - CP: Microbiology
KW - HIV
KW - microbiome
KW - short-chain fatty acids
UR - http://www.scopus.com/inward/record.url?scp=85177023525&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.celrep.2023.113336
DO - https://doi.org/10.1016/j.celrep.2023.113336
M3 - Article
C2 - 37918403
SN - 2211-1247
VL - 42
JO - Cell reports
JF - Cell reports
IS - 11
M1 - 113336
ER -