Gut microbiome in pediatric acute pancreatitis and Crohn's disease versus irritable bowel syndrome and healthy controls.

OBJECTIVES: Pediatric acute pancreatitis (AP), Crohn's disease (CD), and irritable bowel syndrome (IBS) are associated with gut dysbiosis, but differences and similarities between conditions are unknown. We hypothesized that gut microbial ecology would differ across these disorders. METHODS: Stool was collected from 120 subjects (AP [n = 30], CD [n = 29], IBS Rome IV [n = 27], and healthy controls [HC, n = 34]). Shotgun metagenomic sequencing was performed on extracted DNA and taxonomic and functional profiles obtained using sylph and HUMAnN3 with default parameters. RESULTS: Age interquartile range for all participants was 8.1-17.7 years. Shannon diversity was decreased in AP compared to IBS or HC (p < 0.0001) and similar to CD (p = 0.97). CD differed from IBS (p = 0.001) and HC (p < 0.0001) while IBS and HC were similar (p = 0.61). Ordination of the first two principal coordinate analyses axes showed sample clustering by condition (R2 = 0.12, p < 0.001), and differences between all conditions in pairwise comparisons (p < 0.001). Escherichia coli, Ruminococcus gnavus, Staphylococcus aureus, and Thomasciavelia ramosa remained enriched when all conditions (AP, CD, and IBS) were compared as a single group to HC. Using a random forest machine learning algorithm for species relative abundance, the ability to classify a sample to each condition versus all others was highest for CD (area under the receiver operative characteristic curve, AUC = 0.97), followed by AP (AUC = 0.92), HC (AUC = 0.88), and IBS (AUC = 0.83). CONCLUSION: Organic disorders (AP and CD) are associated with significant gut dysbiosis than IBS which appears more like HC. Interventions targeting shifts in commensals in AP and CD may be helpful in improving outcomes in both disorders.