Microbial and metabolic features associated with outcome of infliximab therapy in pediatric Crohn's disease

Gut microbial dysbiosis and altered metabonomics have been implicated in the pathogenesis of Crohn's disease (CD). The aim of our study was to characterize the gut microbiome structure and metabolic activities in pediatric CD patients with different clinical outcomes after infliximab (IFX) therapy. Fecal samples were collected from 20 healthy children and 29 newly diagnosed pediatric CD patients. 16S rRNA/ITS2 gene sequencing and targeted metabolomics analysis were applied to profile the gut bacterial microbiome, mycobiome, and metabolome, respectively. Pediatric CD patients exhibited lower relative abundances of short-chain fatty acids (SCFAs)-producing bacteria including Faecalibacterium, Clostridium clusters IV and XIVb, Roseburia, and Ruminococcus, which were correlated with reduced fecal levels of SCFAs. Decreased unconjugated bile acids (BAs) pool size and a lower unconjugated/conjugated BAs ratio were associated with reduced relative abundances of Bifidobacterium and Clostridium clusters IV and XIVb which contain bile salt hydrolases (BSH) genes. IFX treatment enriched the BSH-producing bacteria in CD subjects, which may explain a decreased level of conjugated BAs and an increase in unconjugated BAs as well as the unconjugated/conjugated BAs ratio. Furthermore, a sustained response (SR) of IFX therapy was associated with higher abundances of Methylobacterium, Sphingomonas, Staphylococcus, and Streptococcus, and higher fecal concentrations of amino acids, including L-aspartic acid, linoleic acid, and L-lactic acid at baseline. Our study suggests that the effects of IFX might be partially mediated by enriching bacteria taxa that producing SCFAs and BSH thereby inhibiting inflammation and restoring the BA metabolism. Some fecal bacteria and metabolites may be predictive of outcomes of IFX therapy for pediatric CD patients.

Automated summary

The study revealed that pediatric CD patients have gut microbial dysbiosis and altered metabolism after IFX therapy, which is related to treatment outcomes. The effects of IFX treatment may be mediated by enriching bacteria taxa that produce SCFAs and BSH, thereby inhibiting inflammation and restoring bile acid metabolism. Some fecal bacteria and metabolites may serve as predictors of IFX therapy outcomes for pediatric CD patients.