Alterations of gut microbiota and metabolites in children with Crohn's disease and their correlation with disease activity.

Background: The disruption of the gut microbiota is a prominent feature seen in children with Crohn's disease (CD), impacting metabolic processes. These factors collectively contribute significantly to the onset and progression of CD. The aim of this study was to assess the variations in gut microbiota and metabolites in children with newly diagnosed CD and those in remission, and to investigate their potential correlation with clinical indexes.

Methods: This was a retrospective study. From June 2018 and March 2024, 57 children with CD admitted to Beijing Children's Hospital were included, and 22 healthy children during the same period were selected as the control group. Their peripheral blood and fecal samples were obtained, and clinical data were collected. Analysis of the fecal microbiota and serum metabolites was conducted using metagenomic sequencing and non-targeted mass spectrometry, respectively, to compare the alteration in children with CD and healthy controls (HCs), and their correlation with clinical indexes.

Results: Analysis of fecal metagenomic sequencing data revealed that the alpha diversity was significantly lower in the newly diagnosed CD group compared to the HC group, whereas it was ameliorated in the CD remission group. The beta diversity showed that the microbial structures of the three groups were obviously separated. Firmicutes was identified as the primary altered bacteria in the microbiota. Specifically, the abundance of Ruminococcus, Faecalimonas, Blautia, and Faecalibacterium were correlated with clinical indexes such as pediatric Crohn's disease activity index (PCDAI). Metabolomic analysis highlighted differences in lipid metabolism, bile acid (BA) metabolism, amino acid metabolism and energy homeostasis between the CD remission and newly diagnosed CD groups. Notably, the levels of citric acid were correlated with clinical indexes such as PCDAI, which was also potential indicator for identifying clinical activity of pediatric CD patients [area under the curve (AUC) =0.77, specificity =0.64, sensitivity =0.83].

Conclusions: The microbial diversity of children with newly diagnosed CD decreased, but then ameliorated in the remission stage. Some short-chain fatty acids (SCFAs)-producing bacteria, lipid metabolites, and energy homeostasis products were associated with clinical indexes. In particular, citric acid demonstrated specific effectiveness in identify clinical activity of pediatric CD patients, which was a potential biomarker. Further exploring the mechanism of energy homeostasis in CD is beneficial to find new therapeutic targets.