Impact of red meat, processed meat and fibre intake on risk of late-onset chronic inflammatory diseases: prospective cohort study on lifestyle factors using the Danish ‘Diet, Cancer and Health’ cohort (PROCID-DCH):protocol

Abstract

IntroductionChronic inflammatory diseases (CIDs) (Crohn’s disease, ulcerative colitis, psoriasis, psoriatic arthritis, rheumatoid arthritis and multiple sclerosis) are diseases of the immune system that have some shared genetic and environmental predisposing factors, but still few studies have investigated the effects of lifestyle on disease risk of several CIDs. The primary aim of this prospective cohort study is to investigate the impact of fibre, red meat and processed meat on risk of late-onset CID, with the perspective that results of this study can contribute in supporting future diet recommendations for effective personalised prevention.Methods and analysisThe study will use data from 57 053 persons from the prospective Danish cohort study ‘Diet, Cancer and Health’ together with National Health Registry data. The follow-up period is from December 1993 to December 2018. Questionnaire data on diet and lifestyle were collected at entry to the Diet, Cancer and Health study. The outcome CID is defined as having a diagnosis of one of the CIDs registered in the National Patient Registry or, for multiple sclerosis, in the Danish Multiple Sclerosis Registry during follow-up and being treated with a drug used for the specific disease. The major outcome of the analyses will be to detect variability in risk of late onset of any CID and, if power allows, disease risk of late onset of each CID diagnosis between persons with different fibre and red meat, and processed meat intake. The outcome will be adjusted for age, sex, body mass index, physical activity, energy, alcohol, fermented dairy products, education, smoking status, hormone replacement therapy and comorbidity.Ethics and disseminationThe study is approved by the Danish Data Protection Agency (2012-58-0018). The core study is an open register-based cohort study. The study does not need approval from the Ethics committee or Institutional Review Board by Danish law. Study findings will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences.Trial registration numberNCT03456206; Post-results.

Dietary Red Meat Adversely Affects Disease Severity in a Pig Model of DSS-Induced Colitis Despite Reduction in Colonic Pro-Inflammatory Gene Expression

“…Diet composition plays a substantial role in the pathogenesis and management of colitis [37], and epidemiologic studies indicate that dietary red meat may be a negative factor in relation to UC [15]. No human dietary intervention studies have investigated such a relationship but the impact of red and processed meat on risk of late-onset chronic inflammatory disease including IBD is currently being evaluated in a large prospective cohort study in Denmark [17]. Although the exact pathophysiological mechanisms in which diet plays a role in IBD development remain unknown, several explanations including its effects on composition of gut microbiota, production of microbial metabolites, alterations in mucosal immunity, and mucosal barrier function have been put forward [38].…”

“…Dietary red meat intake may increase the amount of proteins, peptides and amino acids reaching the colon where they can be metabolized by gut bacteria resulting in formation of branched-chain fatty acids (BCFA), ammonia, phenolic and indolic compounds, biogenic amines, hydrogen sulfide and nitric oxide [16]. A proposed mechanism for a relationship between IBD risk and/or development and red meat intake involves some of these compounds that may induce breakdown of the colonic mucus barrier function so that microbes and toxins may reach the epithelium and activate the immune system [16][17][18][19].…”

“…In the present study, we examined the effect of red meat intake prior and during DSS treatment on DSS-induced colitis symptoms and on systemic and local immune response parameters using a porcine model of experimental UC. The pigs applied in the present study were older (42 days of age) than pigs in previous DSS-model studies [29][30][31][32]34] and their gastrointestinal tracts thereby more mature to better mimic the adult phase of human life where IBD disease onset is at its peak [17]. We hypothesized that dietary meat would aggravate DSS-induced colitis development.…”

“…One of the proposed mechanisms for the negative effect of meat on IBD development is that a high meat intake may increase the amount of proteins, peptides and amino acids reaching the colon where they are metabolized by gut bacteria [16]. Protein fermentation results in the formation of a variety of metabolites that may cause intestinal dysfunction and render the intestinal mucus layer penetrable to, for example, bacteria, by reducing the di-sulfide bonds in the mucus network [16][17][18]. Thus, microbes may reach the epithelium and activate the immune system [19].…”

Intake of dietary fibre, red and processed meat and risk of late-onset Chronic Inflammatory Diseases: A prospective Danish study on the “diet, cancer and health” cohort

“…Based on the concept of a core disease signature, we provided the hypothesis that intake of high fibre/low red and processed meat may protect against inflammation across CIDs [28,29]. Thus, a diet high in meat and low in fibres may impact inflammation by affecting the composition of the gut microbiome [31] (Figure 1).…”