The rectal microbiome in HIV infected Kenyan men who have sex with men (MSM): associations with sexual behaviour and inflammation in the rectum and blood

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Date
2022-07-17
Authors
Gebrebrhan, Henok
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Abstract
HIV infection is responsible for massive destruction of T cells in the gut associated lypmphoid tissue. The damage is irreversible and affects the host immunity allowing the gut homeostasis to be disturbed. This disruption can translate to gut microbiota alterations, microbial translocation and chronic immune activation. Interest in studying the rectal microbiome has since accelerated as alteration to the microbiota has been implicated in diseases and found to be influenced by both the environment and genetics. One of the interesting factors that affect gut microbiota is sexual orientation as it was shown that MSM status had a distinct microbiota than non-MSM. There have been though few studies accounting for sexual behaviour practises and its effect on the gut microbiota and there is also limited research from sub Saharan Africa. In this thesis, we investigated whether HIV and different sexual behaviours are linked to gut microbiota composition in an MSM cohort from Nairobi, Kenya. We found alpha diversity was consistently lower in Kenyan HIV-infected MSM, including those on antiretroviral therapy (ART) compared with HIV-uninfected MSM. Receptive anal sex with several types of sexual partners (paying, regular, casual) was associated with lower Chao1 and Simpson diversity, independent of HIV status. We also hypothesized that MSM engaging in receptive anal sex might have microbial translocation and associated with immune activation due to local trauma to the rectal mucosa. We found limited evidence of markers of MT in HIV infection but that MSM who engage in receptive anal sex had elevated markers of MT that was correlated with systemic CD4+ T cell activation. We also compared differences between adherent bacteria and lumen bacteria by collecting rectal samples before and after enema to resemble fecal and mucosal samples respectively. We found the fecal samples to have less diversity than mucosal samples and that the mucosal samples were associated with systemic CD4+ T cell subsets. These results demonstrate that both HIV infection and receptive anal sex affect the gut microbiome in MSM. We have also shown the feasibility of carrying out rectal sampling that captures mucosal adherent bacteria without the need for biopsies. This thesis adds to the body of knowledge on MSM behavioural effects on the gut microbiota and can be used for strategies to aimed at reducing HIV susceptibility in this high-risk population.
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Keywords
HIV, IMMUNOLOGY, MSM, MICROBIOME
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