Influence of intestinal microbiota on the development of anal precancerous lesions in HIV patients (Q3202007)
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Project Q3202007 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | Influence of intestinal microbiota on the development of anal precancerous lesions in HIV patients |
Project Q3202007 in Spain |
Statements
30,750.0 Euro
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61,500.0 Euro
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50.0 percent
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1 January 2016
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31 March 2020
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FUNDACION INVESTIGACION BIOMEDICA HOSPITAL RAMON Y CAJAL
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40°25'0.12"N, 3°42'12.89"W
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28079
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Los pacientes con VIH muestran una alta prevalencia de infección anal por VPH de alto riesgo y una incidencia muy aumentada de lesiones precancerosas anales y cáncer anal. La infección por VIH se asocia también a disbiosis intestinal, con comunidades bacterianas enriquecidas en genes involucrados en vías pro-inflamatorias, que se correlacionan con marcadores de progresión clínica. El objetivo del estudio es caracterizar la microbiota intestinal asociada al desarrollo de lesiones precancerosas anales (lesión intraepitelial de alto grado, HSIL), determinar los metabolitos bacterianos implicados e identificar potenciales dianas terapéuticas bacterianas. Para ello, se incluirán 50 HSH VIH+ y y 10 HSH VIH- con presencia de infección anal por VPH de alto riesgo que se seguirán durante 12 meses. Se realizarán citologías anales y anoscopia de alta resolución basalmente, a los 6 y 12 meses. Se estudiará en mucosa anal y en heces la composición de la microbiota por ultrasecuenciación de amplicones de rRNA 16S y los metabolitos bacterianos por espectrometría de masas de última generación. Se investigarán las correlaciones con marcadores plasmáticos de inflamación sistémica y de disrupción de integridad intestinal. Se investigarán biomarcadores bacterianos y metabolómicos de desarrollo de HSIL, y se identificarán experimentalmente las bacterias productoras de los metabolitos implicados en el desarrollo de HSIL. (Spanish)
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HIV patients show a high prevalence of high-risk HPV anal infection and a very increased incidence of anal precancerous lesions and anal cancer. HIV infection is also associated with intestinal dysbiosis, with bacterial communities enriched in genes involved in pro-inflammatory pathways, which correlate with markers of clinical progression. The objective of the study is to characterise the intestinal microbiota associated with the development of anal precancerous lesions (high-grade intraepithelial injury, HSIL), to determine the bacterial metabolites involved and to identify potential bacterial therapeutic targets. This will include 50 HSH HIV+ and 10 HSH HIV- with the presence of high-risk HPV anal infection that will be followed for 12 months. Anal cytologies and high resolution anoscopy will be performed at baseline, at 6 and 12 months. The composition of the microbiota by ultrasequencing of 16S rRNA amplicons and bacterial metabolites by state-of-the-art mass spectrometry will be studied in anal mucosa and faeces. Correlations with plasma markers of systemic inflammation and intestinal integrity disruption will be investigated. Bacterial and metabolomic biomarkers of HSIL development will be investigated, and the bacteria that produce the metabolites involved in the development of HSIL will be identified experimentally. (English)
13 October 2021
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Madrid
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Identifiers
PI15_00345
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