Project Details
Projekt
The role of tobacco smoke-induced changes of the microbiome in shaping risk for inflammatory bowel diseases
Subject Area
Gastroenterology
Term
since 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 426660215
The rapidly increasing incidence rate for inflammatory bowel disease (IBD) since world war II cannot be explained by genetics alone. The current hypothesis suggests, that altered environmental factors and changed lifestyle factors are strong contributors to the disease risk. In this context, smoking is believed to play a central role in altering the disease risk for IBD, although quantitative and mechanistic data to support this are still rare. While over 25% of all adults in Germany smoke, about 20% of all pregnant women consume cigarettes, expanding the potential modulation of the disease risk to their children.In the proposed project, we aim to address the hypothesis that tobacco smoke can alter the IBD risk via modulating the microbiome, the epigenome and the transcriptome. Studies published by the applicants provide initial support for the hypothesis. To further test this hypothesis, the applicants will employ state-of-the-art methods established at their institutions. The central element is a mouse model where animals are exposed to a defined amount of tobacco smoke. The project is divided in three parts: i) To quantitatively assess the smoke induced modulation of the microbiome, ii) to analyze the potential causality of the microbiome in the context of altered IBD risk employing fecal transplantation and iii) to quantify the relative contribution of the epigenome in altering the IBD risk as a result of maternal smoking. All methods and infrastructures required to conduct these three work packages are established and available at the applicant’s institutions.With support of the Z-project and the INF-project, the applicants will integrate data generated in subprojects P1, P3, P8, P9 and P10 in order to create a high-resolution picture of how smoking affects individual cell populations, the proeome and the metabolome with its functional consequences for the affected individual.As a long-term goal, the applicants will join forces with the Pediatrics Department of the University Clinic Kiel aiming to compare the stool microbiome of children from mothers who smoked during pregnancy in comparison to children of non-smokers. Knowing that about 75% of all e-cigarette consumers also continue smoking conventional cigarettes in parallel, it is safe to assume that such altered consumption habits will not decrease the relevance of the findings generated in this project.Since the microbiome can be modulated by diet, prebiotics, probiotics and antibiotics the final aim of the study is to define potential intervention targets. These targets will be subjected to a subsequent intervention study in a mouse model in the second funding period.Taken together, the continuation of this project will enable us for the first time to define the clinical relevance of the microbiome in the context of smoking and ulcerative colitis, while also providing a high-resolution picture of the nature of the impact.
DFG Programme
Research Units
