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 alpha 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. Graphical Abstract

Automated summary

Treatment with anti-TNF antibodies leads to changes in bacteriome and metabolome in children with CD, with specific alterations being associated with mucosal healing. However, similar changes were not observed in children with JIA, suggesting that the effects of anti-TNF on gut microbiota may be disease-specific.