Western and carnivorous dietary patterns are associated with greater likelihood of IBD-development in a large prospective population-based cohort

OBJECTIVE: Nutrition plays a role in the development of Crohn's disease (CD) and ulcerative colitis (UC). However, prospective data on nutrition and disease-onset is limited. Here, we analysed dietary patterns and scores to IBD-development in a prospective population-based cohort. DESIGN: We analysed 125,445 participants of whom 224 individuals developed de novo UC and 97 CD over a maximum 14-year follow-up period. Participants answered health-related (also prospectively) and dietary questionnaires (FFQ) at baseline. Principal Component Analysis (PCA) was conducted deriving a-posteriori dietary patterns. Hypotheses-based a-priori dietary scores were also calculated, including the protein score, Healthy Eating Index, LifeLines Diet Score (LLDS) and alternate Mediterranean Diet Score. Logistic regression models were performed between dietary patterns, scores, and IBD-development. RESULTS: PCA identified five dietary patterns. A pattern characterized by high intake of snacks, prepared meals, non-alcoholic beverages, sauces along with low vegetables and fruit consumption was associated with higher likelihood of CD-development (OR: 1.16, 95% CI: 1.03-1.30, p=0.013). A pattern comprising red meat, poultry, and processed meat, was associated with increased likelihood of UC-development (OR: 1.11, 95% CI: 1.01-1.20, p=0.023). A high diet quality score (LLDS) was associated with decreased risk of CD (OR: 0.95, 95% CI: 0.92-0.99, p=0.009). CONCLUSIONS: A Western dietary pattern was associated with a greater likelihood of CD-development and a carnivorous pattern with UC-development, while a relatively high diet quality (LLDS) was protective for CD-development. Our study strengthens the importance of evaluating dietary patterns to aid prevention of IBD in the general population

The impact of the social environment on children's mental health in a prosperous city: an analysis with data from the city of Munich

BACKGROUND: Children with a low socioeconomic position are more affected by mental difficulties as compared to children with a higher socioeconomic position. This paper explores whether this socioeconomic pattern persists in the prosperous German city of Munich which features high quality of life and coverage of children mental health specialists that lies well above the national average and is among the highest in Europe. METHODS: 1,265 parents of preschool children participated in a cross-sectional health survey. They were given a self-administered questionnaire (including socioeconomic variables) and the 'Strengths and Difficulties Questionnaire (SDQ)', a well-established method to identify mental difficulties among children and adolescents. Prevalence estimates for the 'SDQ-Total Difficulties Score' were calculated, with a special focus on differences by parental (resp. household) socioeconomic position. The association between parental education, household income, single parenthood, nationality, and parental working status on one hand, and their children's mental health on the other, was explored using multivariable logistic regression models. The coverage of mental health specialists per 100,000 children aged 14 or younger in the city of Munich was also calculated. RESULTS: In Munich, the distribution of mental health difficulties among children follows the same socioeconomic pattern as described previously at the national level, but the overall prevalence is about 30% lower. Comparing different indicators of socioeconomic position, low parental education and household income are the strongest independent variables associated with mental difficulties among children (OR = 2.7; CI = 1.6 - 4.4 and OR = 2.8; CI = 1.4 - 5.6, respectively). CONCLUSIONS: Socioeconomic differences in the prevalence of childhood mental difficulties are very stable. Even in a city such as Munich, which is characterized by high quality of life, high availability of mental health specialists, and low overall prevalence of these mental difficulties, they are about as pronounced as in Germany as a whole. It can be concluded that the effect of several characteristics of socioeconomic position 'overrules' the effect of a health promoting regional environment

Long-term dietary patterns are associated with pro-inflammatory and anti-inflammatory features of the gut microbiome

Objective The microbiome directly affects the balance of pro-inflammatory and anti-inflammatory responses in the gut. As microbes thrive on dietary substrates, the question arises whether we can nourish an anti-inflammatory gut ecosystem. We aim to unravel interactions between diet, gut microbiota and their functional ability to induce intestinal inflammation. Design We investigated the relation between 173 dietary factors and the microbiome of 1425 individuals spanning four cohorts: Crohn's disease, ulcerative colitis, irritable bowel syndrome and the general population. Shotgun metagenomic sequencing was performed to profile gut microbial composition and function. Dietary intake was assessed through food frequency questionnaires. We performed unsupervised clustering to identify dietary patterns and microbial clusters. Associations between diet and microbial features were explored per cohort, followed by a meta-analysis and heterogeneity estimation. Results We identified 38 associations between dietary patterns and microbial clusters. Moreover, 61 individual foods and nutrients were associated with 61 species and 249 metabolic pathways in the meta-analysis across healthy individuals and patients with IBS, Crohn's disease and UC (false discovery rate Conclusion We identified dietary patterns that consistently correlate with groups of bacteria with shared functional roles in both, health and disease. Moreover, specific foods and nutrients were associated with species known to infer mucosal protection and anti-inflammatory effects. We propose microbial mechanisms through which the diet affects inflammatory responses in the gut as a rationale for future intervention studies

The composition and metabolic potential of the human small intestinal microbiota within the context of inflammatory bowel disease

BACKGROUND AND AIMS: The human gastrointestinal tract harbours distinct microbial communities essential for health. Little is known about small intestinal communities, despite the small intestine playing a fundamental role in nutrient absorption and host-microbe immune homeostasis. We aimed to explore the small intestine microbial composition and metabolic potential, in the context of inflammatory bowel disease (IBD). METHODS: Metagenomes derived from faecal samples and extensive phenotypes were collected from 57 individuals with an ileostomy or ileoanal pouch, and compared with 1178 general population and 478 IBD faecal metagenomes. Microbiome features were identified using MetaPhAn2 and HUMAnN2, and association analyses were performed using multivariate linear regression. RESULTS: Small intestinal samples had a significantly lower bacterial diversity, compared with the general population and, to a lesser extent, IBD samples. Comparing bacterial composition, small intestinal samples clustered furthest from general population samples and closest to IBD samples with intestinal resections. Veillonella atypica, Streptococcus salivarius and Actinomyces graevenitzii were among the species significantly enriched in the small intestine. Predicted metabolic pathways in the small intestine are predominantly involved in simple carbohydrate and energy metabolism, but also suggest a higher proinflammatory potential. CONCLUSION: We described the bacterial composition and metabolic potential of the small intestinal microbiota. The colonic microbiome of IBD patients, particularly with intestinal resections, showed resemblance to that of the small intestine. Moreover, several features characterising the small intestinal microbiome have been previously associated with IBD. These results highlight the importance of studying the small intestinal microbiota to gain new insight into disease pathogenesis

Patient attitudes towards faecal sampling for gut microbiome studies and clinical care reveal positive engagement and room for improvement

Faecal sample collection is crucial for gut microbiome research and its clinical applications. However, while patients and healthy volunteers are routinely asked to provide stool samples, their attitudes towards sampling remain largely unknown. Here, we investigate the attitudes of 780 Dutch patients, including participants in a large Inflammatory Bowel Disease (IBD) gut microbiome cohort and population controls, in order to identify barriers to sample collection and provide recommendations for gut microbiome researchers and clinicians. We sent questionnaires to 660 IBD patients and 112 patients with other disorders who had previously been approached to participate in gut microbiome studies. We also conducted 478 brief interviews with participants in our general population cohort who had collected stool samples. Statistical analysis of the data was performed using R. 97.4% of respondents reported that they had willingly participated in stool sample collection for gut microbiome research, and most respondents (82.9%) and interviewees (95.6%) indicated willingness to participate again, with their motivations for participating being mainly altruistic (57.0%). Responses indicated that storing stool samples in the home freezer for a prolonged time was the main barrier to participation (52.6%), but clear explanations of the sampling procedures and their purpose increased participant willingness to collect and freeze samples (P = 0.046, P = 0.003). To account for participant concerns, gut microbiome researchers establishing cohorts and clinicians trying new faecal tests should provide clear instructions, explain the rationale behind their protocol, consider providing a small freezer and inform patients about study outcomes. By assessing the attitudes, motives and barriers surrounding participation in faecal sample collection, we provide important information that will contribute to the success of gut microbiome research and its near-future clinical applications

Lamin A/C sustains PcG protein architecture, maintaining transcriptional repression at target genes

Beyond its role in providing structure to the nuclear envelope, lamin A/C is involved in transcriptional regulation. However, its cross talk with epigenetic factors--and how this cross talk influences physiological processes--is still unexplored. Key epigenetic regulators of development and differentiation are the Polycomb group (PcG) of proteins, organized in the nucleus as microscopically visible foci. Here, we show that lamin A/C is evolutionarily required for correct PcG protein nuclear compartmentalization. Confocal microscopy supported by new algorithms for image analysis reveals that lamin A/C knock-down leads to PcG protein foci disassembly and PcG protein dispersion. This causes detachment from chromatin and defects in PcG protein-mediated higher-order structures, thereby leading to impaired PcG protein repressive functions. Using myogenic differentiation as a model, we found that reduced levels of lamin A/C at the onset of differentiation led to an anticipation of the myogenic program because of an alteration of PcG protein-mediated transcriptional repression. Collectively, our results indicate that lamin A/C can modulate transcription through the regulation of PcG protein epigenetic factors

Long-Term Dietary Patterns Are Reflected in the Plasma Inflammatory Proteome of Patients with Inflammatory Bowel Disease

Diet plays an important role in the development and progression of inflammatory bowel disease (IBD, comprising Crohn's disease (CD) and ulcerative colitis (UC)). However, little is known about the extent to which different diets reflect inflammation in IBD beyond measures such as faecal calprotectin or C-reactive protein. In this study, we aimed to unravel associations between dietary patterns and circulating inflammatory proteins in patients with IBD. Plasma concentrations of 73 different inflammation-related proteins were measured in 454 patients with IBD by proximity extension assay (PEA) technology. Food frequency questionnaires (FFQ) were used to assess habitual diet. Principal component analysis (PCA) was performed to extract data-driven dietary patterns. To identify associations between dietary patterns and plasma proteins, we used general linear models adjusting for age, sex, BMI, plasma storage time, smoking, surgical history and medication use. Stratified analyses were performed for IBD type, disease activity and protein intake. A high-sugar diet was strongly inversely associated with fibroblast growth factor-19 (FGF-19) independent of IBD type, disease activity, surgical history and deviance from recommended protein intake (false discovery rate (FDR) < 0.05). Conversely, a Mediterranean-style pattern was associated with higher FGF-19 levels (FDR < 0.05). A pattern characterised by high alcohol and coffee intake was positively associated with CCL11 (eotaxin-1) levels and with lower levels of IL-12B (FDR < 0.05). All results were replicated in CD, whereas only the association with FGF-19 was significant in UC. Our study suggests that dietary habits influence distinct circulating inflammatory proteins implicated in IBD and supports the pro- and anti-inflammatory role of diet. Longitudinal measurements of inflammatory markers, also postprandial, are needed to further elucidate the diet-inflammation relationship

Faecal metabolome and its determinants in inflammatory bowel disease

OBJECTIVE: Inflammatory bowel disease (IBD) is a multifactorial immune-mediated inflammatory disease of the intestine, comprising Crohn's disease and ulcerative colitis. By characterising metabolites in faeces, combined with faecal metagenomics, host genetics and clinical characteristics, we aimed to unravel metabolic alterations in IBD.DESIGN: We measured 1684 different faecal metabolites and 8 short-chain and branched-chain fatty acids in stool samples of 424 patients with IBD and 255 non-IBD controls. Regression analyses were used to compare concentrations of metabolites between cases and controls and determine the relationship between metabolites and each participant's lifestyle, clinical characteristics and gut microbiota composition. Moreover, genome-wide association analysis was conducted on faecal metabolite levels.RESULTS: We identified over 300 molecules that were differentially abundant in the faeces of patients with IBD. The ratio between a sphingolipid and L-urobilin could discriminate between IBD and non-IBD samples (AUC=0.85). We found changes in the bile acid pool in patients with dysbiotic microbial communities and a strong association between faecal metabolome and gut microbiota. For example, the abundance of Ruminococcus gnavus was positively associated with tryptamine levels. In addition, we found 158 associations between metabolites and dietary patterns, and polymorphisms near NAT2 strongly associated with coffee metabolism.CONCLUSION: In this large-scale analysis, we identified alterations in the metabolome of patients with IBD that are independent of commonly overlooked confounders such as diet and surgical history. Considering the influence of the microbiome on faecal metabolites, our results pave the way for future interventions targeting intestinal inflammation.</p

Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project

Host genetics are known to influence the gut microbiome, yet their role remains poorly understood. To robustly characterize these effects, we performed a genome-wide association study of 207 taxa and 205 pathways representing microbial composition and function in 7,738 participants of the Dutch Microbiome Project. Two robust, study-wide significant (P < 1.89 × 10-10) signals near the LCT and ABO genes were found to be associated with multiple microbial taxa and pathways and were replicated in two independent cohorts. The LCT locus associations seemed modulated by lactose intake, whereas those at ABO could be explained by participant secretor status determined by their FUT2 genotype. Twenty-two other loci showed suggestive evidence (P < 5 × 10-8) of association with microbial taxa and pathways. At a more lenient threshold, the number of loci we identified strongly correlated with trait heritability, suggesting that much larger sample sizes are needed to elucidate the remaining effects of host genetics on the gut microbiome