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AIDS. 2018 Jul 31;32(12):1589-1598. doi: 10.1097/QAD.0000000000001813.

The microbial metabolite trimethylamine-N-oxide in association with inflammation and microbial dysregulation in three HIV cohorts at various disease stages.

Author information

1
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge.
2
Science for Life Laboratory, Division of Proteomics and Nanobiotechnology, KTH Royal Institute of Technology, Solna.
3
Division of Renal Medicine, Department of Clinical Science Intervention and Technology, Karolinska University Hospital Huddinge, Stockholm, Sweden.
4
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet.
5
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo.
6
Section of Clinical Immunology and Infectious diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.
7
Department of Medicine Huddinge, Unit of Infectious Disease, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Abstract

OBJECTIVE:

HIV-1-infection infers an increased cardiovascular risk where gut dysbiosis and microbial translocation may contribute. We assessed TMAO, a microbial metabolite with atherosclerotic properties, in plasma of HIV-1-infected individuals at different clinical stages in relation to inflammatory markers, cardiovascular events and gut microbiota.

METHODS:

Primary HIV-1-infected (n = 17) and chronic HIV-1-infected individuals (n = 22) were sampled before and after ART-initiation. In the chronic HIV-1-cohort, repeated faecal samples were analysed by 16SrRNA gene sequencing. HIV-1-infected individuals on longstanding ART (n = 101) and healthy HIV-1-negative individuals (n = 60), served as controls. TMAO and markers of immune activation were analysed by LC/MS/MS and immune assays, respectively.

RESULTS:

TMAO levels were lower in untreated HIV-1-infected individuals, increased significantly after ART-initiation (P = 0.040 and P < 0.001) but remained similar to healthy controls. TMAO levels were not affected by ART, immune status or degree of systemic inflammation. Higher TMAO in HIV-1-infected individuals on longstanding ART was not significantly associated with cardiovascular risk (P = 0.38). Additionally, TMAO levels correlated inversely with Bacteroidetes (Rho: -0.62, P = 0.002), and positively with Firmicutes (Rho: 0.65, P = 0.001) but held no correlation to TMA-producing genera. Notably gut dysbiosis at follow-up was more pronounced in patients without increase in TMAO levels after ART characterized by loss of Bacteroidetes (P = 0.023) and significantly elevated LPS levels (P = 0.01).

CONCLUSION:

Our data does not support that TMAO is a significant link between gut dysbiosis and inflammation in HIV-1-infection. We propose that HIV-1, microbial composition and ART disparately confound TMAO levels, thus limiting its role as a cardiovascular risk marker in HIV-1-infected individuals.

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