Short summary

Aims 

- to investigate the impact of lifestyle including diet on developing risk of chronic inflammatory disease (CID) in the UK Biobank cohort 

- to investigate gene-environment (GxE) interactions in relation to risk of CID in the UK Biobank cohort 

- to evaluate results from UK Biobank with results from a similar research project based on the Danish "Diet, Health, and Cancer" with prospectively collected data on lifestyle including information on diet by a food-frequency questionnaire

Hypotheses 

- that the risk of CID will be lower among those with a high  fibre/low red and processed meat intake compared to those with a low fibre/high red and processed meat intake

- that the potential impact of the FUT2 polymorphism with respect to risk of CID will be highest among those with a high  fibre/low red and processed meat intake compared to those with a low fibre/high red and processed meat intake 

Rationale

The CIDs can be considered as systemic diseases which primarily affect one organ (e.g. the intestine for inflammatory bowel disease (IBD)). The peak of disease-onset is in the adult phase of life and the incidences are increasing. The CIDs may share predisposing factors such as e.g. diet. GxE interaction analysis is powerful to identify genes and environment factors that are involved in the development of CID because an interaction suggests that they both factors are involved in the same process. There are many potential mechanisms whereby environment such as diet may affect the immune system either directly or indirectly via e.g. the activity of the gut microbiome. Recently, we provided the hypothesis that intake of high fibre/low red and processed meat may protect against CID (Andersen, Nutrient, 2017). In short, low intake of fibre (which could otherwise serve as a nutrient for the microbes) may lead to the microbial metabolism of mucus and to decrease of the intestinal mucus layer. A high intake of red and processed meat (containing organic sulphur and sulphate additives) may render the mucus layer penetrable to e.g. bacteria by reducing the disulphide bonds in the mucus network. Thus, microbes may reach the epithelium and activate the immune system. There is some support for such this hypothesis, including findings of; high amounts of sulphate-reducing bacteria in IBD patients (Jia, FEMS, 2012, Gibson, Gut, 1993); association of high fibre intake with low risk of IBD in a prospective study (Ananthakrishnan. Gastroenterology 2013); association of high intake of red meat, total protein, and risk of developing inflammatory polyarthritis in a population-based prospective cohort (EPIC-Norfolk) (Pattison, Arthritis and rheumatism, 2004), and association of high meat consumption with relapse of IBD symptoms (Jowett, Gut 2004).

Description of the cohort

UK Biobank

Data and biological material

Genetics, clinical and lifestyle information

Collaborating researchers and departments

Institut for Molekylær Medicin, SDU / IKMB, Kiel Universitet, Germany

•   Professor David Ellinghaus

Genetic Epidemiology, Human Genetics, University of Southern Denmark

•  Professor Qihua Tan

Hospital of Southern Jutland, Institute of Molecular Medicine, University of Southern Denmark 

• Professor Vibeke Andersen