Gut microbiome in hiv-1 infection
- Autores: Muntsa Rocafort
- Directores de la Tesis: Roger Paredes Deiros (dir. tes.), Marc Noguera Julián (dir. tes.)
- Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2018
- Idioma: español
- Tribunal Calificador de la Tesis: Chaysavanh Manichanh (presid.), Sergio Serrano Villar (secret.), Francesca Ceccherini (voc.)
- Programa de doctorado: Programa de Doctorado en Microbiología por la Universidad Autónoma de Barcelona
- Materias:
- Enlaces
- Tesis en acceso abierto en: TDX
- Resumen
Soon after Human Immunodeficiency Virus type 1 (HIV-1) infection, a severe and rapid depletion of the gut-associated lymphoid tissue (GALT) occurs, including significant loss of both, immune and epithelial host cells. This is followed by an increased permeability of the intestinal cell lining which facilitates microbial translocation. Microbial cells and products that are usually contained and controlled within the intestinal lumen, can now circulate in the bloodstream and become a new source for immune activation and inflammation. Because of the significant immune imbalance in the GALT after HIV-1 infection, recent microbiome research has focused on understanding the changes occurring in the microbial communities inhabiting the human gut after HIV-1 perturbation and in response to antiretroviral treatment (ART).
Initial cross-sectional studies provided contradictory associations between gut microbial richness and diversity and HIV-1 infection and suggested shifts from Bacteroides to Prevotella predominance following viral infection. Nonetheless, these results have not been confirmed in animal models or in studies matched for HIV-1 transmission risk groups. For instance, in non-human primate models (NHPM), Simian Immunodeficiency Virus (SIV) infection is followed by expansion of enteric virome but has a limited impact on the gut bacteriome.
In two independent European cross-sectionals cohorts of chronically HIV-1-infected subjects and uninfected controls, in Barcelona (n=156) and Stockholm (n=84), men-who-have-sex-with-men (MSM) showed a Prevotella-enriched gut microbiota and higher microbial richness and diversity compared to non-MSM individuals who predominantly showed a Bacteroides-enriched microbiota, regardless of HIV-1 infection. After stratifying for sexual orientation (MSM vs. non-MSM), we described lower microbial richness and diversity in HIV-1 infected subjects, more so in subjects with an immune-discordant response to ART, but there was no solid evidence of an HIV-1-specific dysbiosis. In our Barcelona cohort, diet did not have a major impact on gut microbiota composition.
To understand the longitudinal effects of HIV-1 infection on the human gut microbiota, we prospectively followed 49 Mozambican subjects diagnosed with recent HIV-1 infection and 54 uninfected controls for 9-18 months and compared them with 98 chronically HIV-1-infected subjects ART-treated (n=27) or not (n=71). Recent HIV-1infection was characterized by increased fecal Adenovirus shedding, which persisted during chronic HIV-1 infection and did not resolve with ART. Recent HIV-1 infection was also followed by transient non-HIV-1-specific changes in the gut bacterial richness and composition. Despite early resilience to change, an HIV-1-specific signature in the gut bacteriome could be eventually identified in chronically HIV-1-infected subjects. Such signature featured depletion of Akkermansia, Anaerovibrio, Bifidobacterium, and Clostridium, and has been previously associated with chronic inflammation, CD8+ T-cell anergy and metabolic disorders.
In conclusion: 1) Sexual practice is an important confounding factor in microbiome studies that needs to be considered, especially in HIV-1-gut microbiota studies; 2) Gut microbiota is initially resilient to change right after HIV-1 acquisition but a pro-inflammatory-bacterial signature eventually appears in chronic phases of the infection, and 3) Changes on the gut microbiota do not only impact bacterial communities, but, at least, also viral communities.
