Multiomics profiling and parenteral nutrition weaning in pediatric patients with intestinal failure: A longitudinal cohort study.

Background: Intestinal failure (IF) is a life-limiting condition that includes a variety of intestinal pathologies. Currently, there are few clinical biomarkers that reflect intestinal function or a patient's potential to wean off parenteral nutrition (PN), making it difficult to predict the clinical trajectory. By associating gut microbiome taxonomic and functional features and blood analytes with the proportion of daily energy delivered via PN-a proxy for intestinal function-our study aimed to discover potential predictors of intestinal function and PN weaning potential.

Methods: In this longitudinal multiomics cohort study, we followed 18 pediatric patients with IF and PN support for ≤1.5 years. Fecal and stoma samples were analyzed using metagenomic shotgun sequencing to assess bacterial taxonomy and function and internal transcribed spacer 2 ribosomal RNA sequencing to characterize the fungal community. Targeted metabolomics was used to quantify 257 blood analytes. Linear mixed models were used to analyze the associations of PN dependence with microbiome features and blood analytes.

Results: The bacterial and fungal taxonomic composition exhibited substantial interpatient and intrapatient variability, with no link to PN dependence. In contrast, bacterial functional analysis revealed 63 MetaCyc pathways significantly associated with PN dependence. Additionally, 32 blood analytes were associated with PN dependence.

Conclusion: In this exploratory study, we found that functional microbiome features and blood metabolomic profiles-particularly urea cycle metabolites, creatinine, asparagine, and tryptophan-derived metabolites-show promise for predicting intestinal function. Furthermore, they may have therapeutic implications for promoting intestinal adaptation. Confirmatory trials with larger sample sizes are needed to validate these findings.