Faecal Bacteriome and Metabolome Profiles Associated with Decreased Mucosal Inflammatory Activity Upon Anti-TNF Therapy in Paediatric Crohn's Disease.

BACKGROUND AND AIMS: Treatment with anti-tumour necrosis factor α antibodies [anti-TNF] changes the dysbiotic faecal bacteriome in Crohn's disease [CD]. However, it is not known whether these changes are due to decreasing mucosal inflammatory activity or whether similar bacteriome reactions might be observed in gut-healthy subjects. Therefore, we explored changes in the faecal bacteriome and metabolome upon anti-TNF administration [and therapeutic response] in children with CD and contrasted those to anti-TNF-treated children with juvenile idiopathic arthritis [JIA]. METHODS: Faecal samples collected longitudinally before and during anti-TNF therapy were analysed with regard to the bacteriome by massively parallel sequencing of the 16S rDNA [V4 region] and the faecal metabolome by 1H nuclear magnetic resonance imaging. The response to treatment by mucosal healing was assessed by the MINI index at 3 months after the treatment started. We also tested several representative gut bacterial strains for in vitro growth inhibition by infliximab. RESULTS: We analysed 530 stool samples from 121 children [CD 54, JIA 18, healthy 49]. Bacterial community composition changed on anti-TNF in CD: three members of the class Clostridia increased on anti-TNF, whereas the class Bacteroidia decreased. Among faecal metabolites, glucose and glycerol increased, whereas isoleucine and uracil decreased. Some of these changes differed by treatment response [mucosal healing] after anti-TNF. No significant changes in the bacteriome or metabolome were noted upon anti-TNF in JIA. Bacterial growth was not affected by infliximab in a disc diffusion test. CONCLUSIONS: Our findings suggest that gut mucosal healing is responsible for the bacteriome and metabolome changes observed in CD, rather than any general effect of anti-TNF.

Incidence of Crohn disease in the Czech Republic in the years 1990 to 2001 and assessment of pediatric population with inflammatory bowel disease.

BACKGROUND: The aim of this study was to assess the pediatric population that suffered from inflammatory bowel disease (IBD) in the Czech Republic and to determine the incidence of Crohn disease (CD) in children up to 15 years age between 1990 and 2001. METHODS: Diagnostic criteria for CD, ulcerative colitis (UC), and indeterminate colitis (IC) were defined. Medical records provided a source of basic information about the children. A standardized protocol was filled out and sent to the coordinator of the study. All protocols were checked to see whether the data corresponded to the defined criteria and then were processed further. The study was retrospective in character for the years 1990 to 1999 and prospective for the years 2000 and 2001. RESULTS: Diagnostic criteria were met in 470 patients with IBD; 201 of them turned 18 years old during the study period. CD was diagnosed in 223 patients. The incidence of CD in children up to 15 years of age increased from 0.25/100,000 in 1990 to 1.25/100,000 in 2001. Eighty-two percent of children with CD were treated with aminosalicylates in combination with corticosteroids; 29% of patients received azathioprine. Severe growth retardation was recorded in 6.4% of adolescents with CD at the age of 18. UC was diagnosed in 202 patients. Therapy with aminosalicylates only was sufficient for control of the disease in 23% patients; 68% children were treated with corticosteroids, 15 of them (23% of the whole group) received additional azathioprine. Criteria for IC were met in 9.8% of all patients with IBD. CONCLUSION: This study confirmed an increase in incidence of CD in children younger than 15 years in the Czech Republic.