An investigation led by scientists at the Joint Research Unit on Genomics and Health of FISABIO, a biomedical research foundation of the Valencian government, and the Cavanilles Institute of Biodiversity and Evolutionary Biology of the University of Valencia shows how the altered metabolism of gut microbiota contributes to worsen health in HIV-infected patients. The findings of this study have been recently published in Mucosal Immunology, of Nature Publishing Group.
The objective of research was to determine the gene and taxonomic composition of intestinal microbiota in patients infected with the human immunodeficiency virus (HIV) with a positive response to antiviral therapy and how changes affected their health. This way, scientists found out that there was not only a change in the species of intestinal bacterial communities, but also their metabolic capacity was altered.
“These functional changes in the microbiota include increased potentially pathogenic metabolic pathways, pathways of resistance to oxidative stress and an increased production pathway of lipopolysaccharides, a key component of the membrane of gram-negative bacteria which is highly inflammatory”, explains the first author, Jorge Francisco Vázquez Castellanos.
The study was conducted with a cohort of HIV-infected patients with a positive response to antiretroviral therapy and with control individuals of the same age and gender as those infected. First, researchers measured their clinical variables relating to immune system, atherosclerosis, inflammation and cardiovascular risk, and then they performed a metagenomic analysis of their intestinal bacterial communities. Finally, they established correlations between the changes in bacterial communities and the health and immune system indicators.
This study is the result of interdisciplinary collaboration between researchers from the Joint Research Unit on Genomics and Health of FISABIO and the Cavanilles Institute of Biodiversity and Evolutionary Biology – Amparo Latorre, José María Gosalbes, Andrés Moya and Jorge F. Vázquez Castellanos and Dr Sergio Serrano-Villar, from the Service of Infectious Diseases of the Ramón y Cajal University Hospital.
Increased Life Expectancy
Antiretroviral therapy in HIV-infected patients has proven very effective, as life expectancy has increased significantly. However, it continues to be ten years shorter than that of the general population and it is estimated that this virus kills about 1.5 million people each year. The most common causes of death in infected patients include cardiovascular diseases related to atherosclerosis.
“Although the causes of this systemic inflammation may be varied, it is thought that one of the main could be the translocation of bacterial metabolites into the bloodstream due to damage caused by the virus to the intestinal mucosa. That is why it is important to characterise the microbiota in HIV-infected patients and to study the relationship between these changes and the deterioration of their health”, argues Andrés Moya, Professor of Genetics at the University of Valencia and researcher of the Joint Unit with FISABIO.
The next step in research is to conduct similar analyses on different groups of patients with different responses to antiretroviral treatment and understand the fundamental changes that can cause these aberrant bacterial communities. In addition, Jorge Vázquez has emphasised that the application of prebiotics or probiotics to control this altered bacterial community “could be of great help to prevent chronic damage of patients on antiretroviral therapy and, certainly, a very promising field of study”.
Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals, Vázquez-Castellanos J.F., Serrano-Villar S., Latorre A., Artacho A., Ferrús ML., Madrid N., Vallejo A., Sainz T., Martínez-Botas J., Ferrando-Martínez S., Vera M., Dronda F., Leal M., Del Romero J., Moreno S., Estrada V., Gosalbes MJ., Moya A. Mucosal Immunology, doi: 10.1038/mi.2014.107, published 19 November 2014.
Source: RUVID Association