Network-based multi-omics integration reveals metabolic at-risk profile within treated HIV-infection

Flora Mikaeloff*, Marco Gelpi, Rui Benfeitas, Andreas D. Knudsen, Beate Vestad, Julie Høgh, Johannes R. Hov, Thomas Benfield, Daniel D. Murray, Christian G. Giske, Adil Mardinoglu, Marius Trøseid, Susanne D. Nielsen, Ujjwal Neogi

*Corresponding author af dette arbejde

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Abstract

Multiomics technologies improve the biological understanding of health status in people living with HIV on antiretroviral therapy (PWH). Still, a systematic and in-depth characterization of metabolic risk profile during successful long-term treatment is lacking. Here, we used multi-omics (plasma lipidomic, metabolomic, and fecal 16 S microbiome) data-driven stratification and characterization to identify the metabolic at-risk profile within PWH. Through network analysis and similarity network fusion (SNF), we identified three groups of PWH (SNF-1–3): healthy (HC)-like (SNF-1), mild at-risk (SNF-3), and severe at-risk (SNF-2). The PWH in the SNF-2 (45%) had a severe at-risk metabolic profile with increased visceral adipose tissue, BMI, higher incidence of metabolic syndrome (MetS), and increased di- and triglycerides despite having higher CD4+ T-cell counts than the other two clusters. However, the HC-like and the severe at-risk group had a similar metabolic profile differing from HIV-negative controls (HNC), with dysregulation of amino acid metabolism. At the microbiome profile, the HC-like group had a lower α-diversity, a lower proportion of men having sex with men (MSM) and was enriched in Bacteroides. In contrast, in at-risk groups, there was an increase in Prevotella, with a high proportion of MSM, which could potentially lead to higher systemic inflammation and increased cardiometabolic risk profile. The multi-omics integrative analysis also revealed a complex microbial interplay of the microbiome-associated metabolites in PWH. Those severely at-risk clusters may benefit from personalized medicine and lifestyle intervention to improve their dysregulated metabolic traits, aiming to achieve healthier aging.
OriginalsprogEngelsk
Artikelnummere82785
TidsskrifteLife
Vol/bind12
Antal sider25
ISSN2050-084X
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The study is funded by the Swedish Research Council grants 2017-01330, 2018-06156, and 2021-01756 to U.N. Novo Nordic Foundation, Lundbeck Foundation, Augustinus Foundation, Region

Funding Information:
Hovedstaden, and Rigshospitalet Research Council to SDN. DDM acknowledges the support received from Danish National Research Foundation Grant 126 (DNRF126).

Publisher Copyright:
© 2023, eLife Sciences Publications Ltd. All rights reserved.

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