Study of the intestinal microbiota in the hiv infection and the effect of a nutritional intervention
- Autores: Jorge F. Vázquez Castellanos
- Directores de la Tesis: Andrés Moya Simarro (dir. tes.), Amparo Latorre (codir. tes.), María José Gosalbes Soler (codir. tes.)
- Lectura: En la Universitat de València ( España ) en 2017
- Idioma: español
- Tribunal Calificador de la Tesis: María del Mar Masiá Canuto (presid.), Pilar Francino Puget (secret.), Miguel Pignatelli Moreno (voc.)
- Programa de doctorado: Programa Oficial de Doctorado en Biotecnología
- Materias:
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- Resumen
The use of ART in HIV+ subjects has increased considerably the life expectancy restoring the CD4+ T-cell counts and maintaining at low levels the viral load. However, their life expectancy is 10 years lower than the average population. This reduction is given due to unrelated AIDS illness, such as cardiovascular diseases and atherosclerosis that are caused by persistent immune activation and chronic inflammation. A possible explanation for this phenomenon is a constant bacterial translocation from the intestinal lumen to the systemic circulation given a prior disruption of the GALT. Moreover, the loss of the lymphoid tissue leads to a microbial imbalance that could be related to the systemic immune activation.
In the present thesis, we describe in a holistic way the fundamental role of the microbiome in the pathogenesis of HIV infection. Here we present the results of a cross-sectional study of a cohort of three different HIV-infected groups of subjects (with a different response to the ART) and controls target to understand the alterations of the gut-microbiome given the HIV infection. The microbiome was characterized implementing different “omic” technologies and the impact on the host health was determined based on measuring clinical data related to the immune response and the bacterial translocation. Finally, a pilot study based on dietary supplementation with prebiotics and glutamine was carried out with the aim of ameliorating the HIV-associated dysbiosis.
The HIV infection causes a disruption of the GALT leading the dysbiosis of the microbial community that cannot be restored by the ART. Moreover, the infection time would affect the diversity of the microbiota and the ecosystem stability. This dysbiotic community is enriched in Gram-negative species which are adapted to the inflammatory environment of the gut produced by HIV infection and produces pro-inflammatory metabolites which trigger the systemic immune activation and inflammation. Moreover, the HIV-dysbiosis is depleted for SCFA producer species and in the expression of genes related to anti-inflammatory metabolic pathways such as butanoate metabolism, propanoate metabolism or fatty acid metabolism.
The prebiotic has an effect on a community whose original configuration is receptive to the nutritional intervention; this is related to the time exposure to HIV infection. The prebiotic intervention increases the butyrate levels by means of the increase of SCFA-producer species such as Faecalibacterium sp. The increment of the levels of the butyrate is related to the decrease of the bacterial translocation and systemic inflammation.
Finally, we show that the dysbiotic-community is able to establish a stable-community which is associated with the deterioration of the patient's health. More importantly, we suggest that the microbiota may be a new target for clinical interventions in patients infected with HIV and proposed putative candidates for been viable targets for such interventions.
