The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
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Digital Trial Lecture - time and place
Adjudication committee
- First opponent: Section Chief Roger Paredes, Institut de Recerca de la Sida IrsiCaixa, Barcelona, Spain
- Second opponent: Professor An Hendrix, University of Gent, Belgium
- Third member and chair of the evaluation committee: Professor Marit Inngjerdingen, Institute of Clinical Medicine, University of Oslo
Chair of defence
Professor Tone Tønjum, Institute of Clinical Medicine, University of Oslo
Principal Supervisor
Associate Professor Marius Trøseid, Institute of Clinical Medicine, University of Oslo
Summary
Despite effective antiretroviral treatment, people living with HIV (PLWH) have reduced life expectancy. Gut microbiota alterations, chronic inflammation and increased risk of cardiometabolic disorders, such as abdominal obesity, metabolic syndrome and type 2 diabetes (T2D), have been reported in PLWH.
Extracellular vesicles (EVs) have emerged as important modulators of intercellular communication and microbe-host crosstalk. Gut microbes may utilize EVs to transfer toxic components from the gut to the circulation, such as lipopolysaccharides (LPS), thus inducing host immune responses.
This thesis has explored the interplay between the HIV-related gut microbiota and risk of comorbidities. We investigated the effect of probiotic intervention, and explored the potential role of EVs as mediators of microbe-host crosstalk. We found that reduced Enterobacteriaceae after probiotic intervention support a local anti-inflammatory effect in the gut. However, the lacking systemic effect does not support a clear beneficial effect on microbial composition in HIV infection.
Moreover, we identified an HIV-related microbiota signature, independently of confounders, which correlated closely with higher risk of metabolic syndrome and abdominal obesity. The associations were driven by increased Desulfovibrionaceae and decrease in several Clostridia.
We further explored EVs as disease biomarkers, first by evaluating analytical variation in analysis of EVs by nanoparticle tracking analysis, then by studying their role in relation to microbial translocation and increased cardiovascular risk in individuals with HIV and T2D. Individuals with HIV and T2D had elevated plasma EV levels, which strongly correlated with plasma LPS, triglycerides and Framingham score, but not with gut microbiota alterations. The proteomic content of plasma EVs was largely related to cardiometabolic disease genes and upstream regulation of central inflammatory pathways, and several bacterial proteins were identified.
Additional information
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