(P15) The microbial metabolite TMAO in association with inflammation and microbial dysregulation in three HIV cohorts at various disease stages

Författare/Medförfattare

Catharina MISSAILIDIS[1] , Göran Bratt [2], Ujjwal NEOGI [1,3] , Peter STENVINKEL [4] MariusTRØSEID [5,6,7], Piotr NOWAK [8]*, Peter BERGMAN [1]*

Affiliates

[1] Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden. [2] Venhälsan, Department of Venhälsan/Infectious Disease clinic, Södersjukhuset, Stockholm, Sweden [3] Science for Life Laboratory, Division of Proteomics and Nanobiotechnology, KTH Royal Institute of Technology, Solna, Stockholm, Sweden. [4] Department of Clinical Science Intervention and Technology. Division of Renal Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden [5] Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway. [6] Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway, [7] Section of Clinical Immunology and Infectious diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway. [8] Department of Medicine Huddinge, Unit of Infectious Disease, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Abstrakt

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.