(P15) The microbial metabolite TMAO in association with inflammation and microbial dysregulation in three HIV cohorts at various disease stages
Catharina MISSAILIDIS , Göran Bratt , Ujjwal NEOGI [1,3] , Peter STENVINKEL  MariusTRØSEID [5,6,7], Piotr NOWAK *, Peter BERGMAN *
 Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden.  Venhälsan, Department of Venhälsan/Infectious Disease clinic, Södersjukhuset, Stockholm, Sweden  Science for Life Laboratory, Division of Proteomics and Nanobiotechnology, KTH Royal Institute of Technology, Solna, Stockholm, Sweden.  Department of Clinical Science Intervention and Technology. Division of Renal Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden  Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.  Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway,  Section of Clinical Immunology and Infectious diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.  Department of Medicine Huddinge, Unit of Infectious Disease, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
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
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.
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).
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.