Abnormal composition of intestinal bacteria —“dysbiosis”— is characteristic of Crohn’s disease. Disease treatments include dietary changes and immunosuppressive anti-TNFα antibodies as well as ancillary antibiotic therapy but their effects on microbiota composition are undetermined. Using shotgun metagenomic sequencing, we analyzed fecal samples from a prospective cohort of pediatric Crohn’s disease patients starting therapy with enteral nutrition or anti-TNFα antibodies and reveal the full complement and dynamics of bacteria, fungi, archaea and viruses during treatment. Bacterial community membership was associated independently with intestinal inflammation, antibiotic use, and therapy. Antibiotic exposure was associated with increased dysbiosis, whereas dysbiosis decreased with reduced intestinal inflammation. Fungal proportions increased with disease and antibiotic use. Dietary therapy had independent and rapid effects on microbiota composition distinct from other stressor-induced changes and effectively reduced inflammation. These findings reveal that dysbiosis results from independent effects of inflammation, diet, and antibiotics and shed light on Crohn disease treatments.

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Summary Background Stricturing and penetrating complications account for substantial morbidity and health-care costs in paediatric and adult onset Crohn’s disease. Validated models to predict risk for complications are not available, and the effect of treatment on risk is unknown. Methods We did a prospective inception cohort study of paediatric patients with newly diagnosed Crohn’s disease at 28 sites in the USA and Canada. Genotypes, antimicrobial serologies, ileal gene expression, and ileal, rectal, and faecal microbiota were assessed. A competing-risk model for disease complications was derived and validated in independent groups. Propensity-score matching tested the effect of anti-tumour necrosis factor α (TNFα) therapy exposure within 90 days of diagnosis on complication risk. Findings Between Nov 1, 2008, and June 30, 2012, we enrolled 913 patients, 78 (9%) of whom experienced Crohn’s disease complications. The validated competing-risk model included age, race, disease location, and antimicrobial serologies and provided a sensitivity of 66% (95% CI 51–82) and specificity of 63% (55–71), with a negative predictive value of 95% (94–97). Patients who received early anti-TNFα therapy were less likely to have penetrating complications (hazard ratio [HR] 0·30, 95% CI 0·10–0·89; p=0·0296) but not stricturing complication (1·13, 0·51–2·51; 0·76) than were those who did not receive early anti-TNFα therapy. Ruminococcus was implicated in stricturing complications and Veillonella in penetrating complications. Ileal genes controlling extracellular matrix production were upregulated at diagnosis, and this gene signature was associated with stricturing in the risk model (HR 1·70, 95% CI 1·12–2·57; p=0·0120). When this gene signature was included, the model’s specificity improved to 71%. Interpretation Our findings support the usefulness of risk stratification of paediatric patients with Crohn’s disease at diagnosis, and selection of anti-TNFα therapy. Funding Crohn’s and Colitis Foundation of America, Cincinnati Children’s Hospital Research Foundation Digestive Health Center.

Intestinal microbiota is known to be important in health and disease. Its composition is influenced by both environmental and host factors. Few large-scale studies have evaluated the association between host genetic variation and the composition of microbiota. We recruited a cohort of 1,561 healthy individuals, of whom 270 belong in 123 families, and found that almost one-third of fecal bacterial taxa were heritable. In addition, we identified 58 SNPs associated with the relative abundance of 33 taxa in 1,098 discovery subjects. Among these, four loci were replicated in a second cohort of 463 subjects: rs62171178 (nearest gene UBR3) associated with Rikenellaceae, rs1394174 (CNTN6) associated with Faecalibacterium, rs59846192 (DMRTB1) associated with Lachnospira, and rs28473221 (SALL3) associated with Eubacterium. After correction for multiple testing, 6 of the 58 associations remained significant, one of which replicated. These results identify associations between specific genetic variants and the gut microbiome.

The IMPACT questionnaire is a valid and reliable reflection of health-related quality of life of older children and adolescents with both ulcerative colitis and Crohn's disease.

PCDAI scores accurately reflect disease activity as assessed by physician global assessment. A PCDAI score of > or = 30 has acceptable sensitivity and specificity to indicate disease of moderate/severe activity. A PCDAI decrease of 12.5 points or greater following therapeutic intervention accurately reflects a clinically significant response. The PCDAI is an appropriate tool for intervention trials in Crohn disease in children.

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Objectives:The incidence of pediatric-onset inflammatory bowel disease (IBD) is increasing worldwide. We used population-based health administrative data to determine national Canadian IBD incidence, prevalence, and trends over time of childhood-onset IBD.Methods:We identified children <16 years (y) diagnosed with IBD 1999–2010 from health administrative data in five provinces (Alberta, Manitoba, Nova Scotia, Ontario, Quebec), comprising 79.2% of the Canadian population. Standardized incidence and prevalence were calculated per 100,000 children. Annual percentage change (APC) in incidence and prevalence were determined using Poisson regression analysis. Provincial estimates were meta-analyzed using random-effects models to produce national estimates.Results:5,214 incident cases were diagnosed during the study period (3,462 Crohn’s disease, 1,382 ulcerative colitis, 279 type unclassifiable). The incidence in Canada was 9.68 (95% CI 9.11 to 10.25) per 100,000 children. Incidence was similar amongst most provinces, but higher in Nova Scotia. APC in incidence did not significantly change over the study period in the overall cohort (+2.06%, 95% CI −0.64% to +4.76%). However, incidence significantly increased in children aged 0–5y (+7.19%, 95% +2.82% to +11.56%). Prevalence at the end of the study period in Canada was 38.25 (95% CI 35.78 to 40.73) per 100,000 children. Prevalence increased significantly over time, APC +4.56% (95% CI +3.71% to +5.42%).Conclusions:Canada has amongst the highest incidence of childhood-onset IBD in the world. Prevalence significantly increased over time. Incidence was not statistically changed with the exception of a rapid increase in incidence in the youngest group of children.