Effects of different antiretroviral treatments on gut microbiota of hiv-infected patients
The human gut microbiota has a symbiotic relationship with the host and plays a crucial role in the maintenance of health. HIV infection has been associated with a disturbance in gut microbiota (dysbiosis). Increased bacterial translocation and alterations to gut microbiota composition have been obs...
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Universidad de La Rioja (España)
2018
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The human gut microbiota has a symbiotic relationship with the host and plays a crucial role in the maintenance of health. HIV infection has been associated with a disturbance in gut microbiota (dysbiosis). Increased bacterial translocation and alterations to gut microbiota composition have been observed in HIV-infected patients and contribute to immune activation and inflammation. This Doctoral Thesis demonstrates, in clinical practice, that not only HIV infection has effects on gut physiology and microbial profile, but also different combined antiretroviral therapies modify gut microbiota composition. From all the combinations tested in this study, INSTI-based antiretroviral therapy was associated with levels of systemic inflammation and bacterial translocation similar to uninfected controls, suggesting a healthier gut and potentially lesser HIV-related complications. In vitro, Maraviroc did not exert any bacteriostatic effect in the tested strains, and no significant effects were either found in gut microbiota composition when administered to mice fed a standard diet, while several and interesting actions were observed when administered to high-fat diet fed-mice. Although Maraviroc is not actually prescribed as monotherapy, if its immunological actions could be potentiated if administered along with a high fat diet deserves further investigation. Finally, we have also demonstrated that other factors that increase the morbidity and mortality of these patients, such as the coinfection with hepatotropic viruses and the metabolic syndrome, also affects the gut flora, although to a lesser extent than HIV infection itself. However, these effects are not mild and highlight the need for monitoring these patients even after immunological control with combined antiretroviral therapies. |
| author2 |
Oteo Revuelta, José Antonio (null) |
| author_facet |
Oteo Revuelta, José Antonio (null) Villanueva-Millán, M. J. |
| format |
text (thesis) |
| author |
Villanueva-Millán, M. J. |
| spellingShingle |
Villanueva-Millán, M. J. Effects of different antiretroviral treatments on gut microbiota of hiv-infected patients |
| author_sort |
Villanueva-Millán, M. J. |
| title |
Effects of different antiretroviral treatments on gut microbiota of hiv-infected patients |
| title_short |
Effects of different antiretroviral treatments on gut microbiota of hiv-infected patients |
| title_full |
Effects of different antiretroviral treatments on gut microbiota of hiv-infected patients |
| title_fullStr |
Effects of different antiretroviral treatments on gut microbiota of hiv-infected patients |
| title_full_unstemmed |
Effects of different antiretroviral treatments on gut microbiota of hiv-infected patients |
| title_sort |
effects of different antiretroviral treatments on gut microbiota of hiv-infected patients |
| publisher |
Universidad de La Rioja (España) |
| publishDate |
2018 |
| url |
https://dialnet.unirioja.es/servlet/oaites?codigo=151018 |
| work_keys_str_mv |
AT villanuevamillanmj effectsofdifferentantiretroviraltreatmentsongutmicrobiotaofhivinfectedpatients |
| _version_ |
1718346670929870848 |
| spelling |
oai-TES00000228572019-04-26Effects of different antiretroviral treatments on gut microbiota of hiv-infected patientsVillanueva-Millán, M. J.The human gut microbiota has a symbiotic relationship with the host and plays a crucial role in the maintenance of health. HIV infection has been associated with a disturbance in gut microbiota (dysbiosis). Increased bacterial translocation and alterations to gut microbiota composition have been observed in HIV-infected patients and contribute to immune activation and inflammation. This Doctoral Thesis demonstrates, in clinical practice, that not only HIV infection has effects on gut physiology and microbial profile, but also different combined antiretroviral therapies modify gut microbiota composition. From all the combinations tested in this study, INSTI-based antiretroviral therapy was associated with levels of systemic inflammation and bacterial translocation similar to uninfected controls, suggesting a healthier gut and potentially lesser HIV-related complications. In vitro, Maraviroc did not exert any bacteriostatic effect in the tested strains, and no significant effects were either found in gut microbiota composition when administered to mice fed a standard diet, while several and interesting actions were observed when administered to high-fat diet fed-mice. Although Maraviroc is not actually prescribed as monotherapy, if its immunological actions could be potentiated if administered along with a high fat diet deserves further investigation. Finally, we have also demonstrated that other factors that increase the morbidity and mortality of these patients, such as the coinfection with hepatotropic viruses and the metabolic syndrome, also affects the gut flora, although to a lesser extent than HIV infection itself. However, these effects are not mild and highlight the need for monitoring these patients even after immunological control with combined antiretroviral therapies.La microbiota intestinal tiene una relación simbiótica con el hospedador y juega un papel muy importante en el mantenimiento de la salud. La infección por el VIH induce una disbiosis intestinal. Varios estudios han demostrado que los pacientes infectados por el VIH presentan alteraciones en la integridad y funcionalidad del tejido gastrointestinal, un incremento en la translocación bacteriana y alteraciones en la composición de la microbiota intestinal, todo lo cual contribuye a una inmunoactivación y, con ello, a un estado inflamatorio crónico. Esta Tesis Doctoral demuestra que no solamente la infección por el VIH tiene efectos sobre la fisiología intestinal y el perfil de la microbiota, sino que también las diferentes terapias antirretrovirales empleadas en la práctica clínica pueden alterar la composición de la microbiota intestinal. De todas las terapias analizadas en este estudio, la basada en los inhibidores de la integrasa se asoció con niveles de inflamación sistémica y translocación bacteriana similar a la de los controles no infectados por el VIH, lo que sugiere la presencia en estos pacientes de un intestino más sano y una menor probabilidad de desarrollo de complicaciones relacionadas con el VIH. In vitro, el fármaco antirretroviral Maraviroc no ejerció ningún efecto bacteriostático en las cepas testadas, y tampoco se encontraron efectos significativos en la composición de la microbiota intestinal cuando se administró en ratones alimentados con una dieta estándar. Sin embargo, este fármaco unido a la ingesta de una dieta alta en grasa se asoció con varias alteraciones del perfil microbiano gastrointestinal. En este sentido, aunque Maraviroc no se prescribe actualmente como monoterapia, sus acciones inmunológicas podrían ser potenciadas al administrarse junto con una dieta alta en grasa. Esta observación debería ser investigada en el futuro. Finalmente, se ha demostrado que otros factores que incrementan la morbi-mortalidad de estos pacientes, como la coinfección por virus hepatotropos y el síndrome metabólico, también afectan a la composición de la flora intestinal, aunque en menor medida que la propia infección por el VIH. Sin embargo, estos efectos no son leves y parecen resaltar la necesidad de monitorizar estos pacientes incluso después del control inmunológico con las terapias antirretrovirales.Universidad de La Rioja (España)Oteo Revuelta, José Antonio (null)Pérez Matute, Patricia (null)2018text (thesis)application/pdfhttps://dialnet.unirioja.es/servlet/oaites?codigo=151018engLICENCIA DE USO: Los documentos a texto completo incluidos en Dialnet son de acceso libre y propiedad de sus autores y/o editores. Por tanto, cualquier acto de reproducción, distribución, comunicación pública y/o transformación total o parcial requiere el consentimiento expreso y escrito de aquéllos. Cualquier enlace al texto completo de estos documentos deberá hacerse a través de la URL oficial de éstos en Dialnet. Más información: https://dialnet.unirioja.es/info/derechosOAI | INTELLECTUAL PROPERTY RIGHTS STATEMENT: Full text documents hosted by Dialnet are protected by copyright and/or related rights. 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