H2020Индивидуална стипендия2018–2020

MECoCaM · Human gut Microbiome, gene Expression and Colorectal Cancer: Assigning causal roles from a novel Mendelian randomization perspective.

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2018-09-03 → 2020-09-02
Финансиране от ЕС: 158 122 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Връзката между бактериите в червата и риска от рак на дебелото черво се анализира чрез генетични методи. Резултатите помагат да се разбере как микробиомът влияе върху генната експресия, което е основа за бъдещи терапии при чревни заболявания.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Human gut Microbiome, gene Expression and Colorectal Cancer: Assigning causal roles from a novel Mendelian randomization perspective.

Colorectal cancer (CRC) is the fourth leading cause of cancer-related deaths in the world and its burden is expected to increase by 60% to more than 1.1 million cancer deaths by 2030. Among CRC risk factors, the contribution of the microbial ecosystem in the gut (gut microbiome) to CRC is not well understood. Some correlations between a microbe and cancer stages have been observed, but only Fusobacterium has shown consistent evidence as risk factor. Additionally, the enrichment of a microbe at a tumour site does not directly assume causation. Rather, microbes may find a carcinogenic ambient as underused nutritional niche (reverse causation) or external exposures can be independently influencing both microbial and host cell proliferation (confounding). In order to reveal causal associations between microbiota and CRC risk and its biological mechanism, in this project, we assessed the potential causal effect of microbiota on host colon gene expression and on CRC risk, using genetic instruments under a Mendelian randomization approach. The results did not clarify the role of microbiota to CRC risk; however, their reflected the effect of the gut microbiota composition in the gene expression of a healthy colon tissue. This can be used as a reference dataset for microbiome-based therapies in colon diseases, such as CRC and inflammatory bowel diseases.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

The contribution of the gut microbial ecosystem to colorectal cancer (CRC) is not well understood. Inflammatory processes and unbalance cell proliferation in the host could be behind observed correlations between a microbe and cancer stages. However, the enrichment of a microbe at a tumour site does not directly assume causation. Rather, this could be the result of a reverse causation or a confounding third factor. Therefore, two major challenges unravelling CRC aetiology are (i) to identify the mechanistic interactions of microbial communities with host intestinal epithelium cells, and (ii) to assign causality to carcinogenesis. These are the aims of this project integrating different “omic” data, and using a Mendelian randomization (MR) approach.In this study we analyse microbiome sequencing data, from up to 500 normal colon mucosa biopsies, to provide a comprehensive description of the gut microbiome. Additionally, we integrate transcriptomic data from these well phenotyped 500 samples to understand the interaction between microbes and the gut epithelial cells. Finally, using the germ-line genetic variation of host cells as a third “omic” layer, the correlations between microbes and (i) environmental exposures, (ii) gene expression, and (iii) CRC can be validated by MR. MR is an analytical approach whereby germ-line genetic markers are used as proxies – or instrumental variables – for putative risk factors. These genetic markers cannot be influenced by reverse causation, and, assuming an absence of pleiotropy, can provide unconfounded estimates of association. Therefore, a MR association between genetic proxies and the outcome of interest would indicate that the exposure being proxied is associated in a causal manner.The identification of the functional relevance and key mediators of gut microbiome to colorectal cancer development is going to increase the development of therapeutic approaches and prevention strategies.

Оригинален текст от CORDIS (на английски).

Участници

FUNDACIO INSTITUT D'INVESTIGACIO BIOMEDICA DE BELLVITGE · L'Hospitalet De LlobregatКоординаторИспания