Acute pancreatitis gut dysbiosis persists at 1-year follow-up and is associated with clinical outcomes

Abstract

Objectives: Pediatric acute pancreatitis (AP) is associated with gut dysbiosis. We aimed to determine if dysbiosis persisted during follow-up and whether it is associated with clinical outcomes.

Methods: Prospective enrollment of participants <21 years with first AP. Stool samples were obtained at baseline (n = 41), 3 months (n = 19), and 12 months (n = 12) and in healthy controls (HC; n = 34). Evaluation for diabetes (DM) or prediabetes (pre-DM) was performed. At 12-month follow-up gastrointestinal (GI) symptom surveys were completed and AP recurrence-acute recurrent pancreatitis (ARP) recorded. Shotgun metagenomic sequencing was performed on extracted microbial DNA.

Results: Microbial alpha diversity was lower for AP versus HC at all three time points (p < 0.008). Bray-Curtis ordinations showed the AP cohort did not cluster by time point, highlighting similarity in microbial composition over time. Within 12-month follow-up: 7/44 participants developed pre-DM/DM, 7/42 developed ARP, 16 had zero or one while 15 had multiple GI symptoms. Distinct clustering of samples was observed in the baseline samples of the group that developed ARP (p = 0.023) and in follow-up samples with multiple GI symptoms, p < 0.05. Relative abundance of most species was lower in AP samples when compared to HC at all time points with enrichment in Ruminococcus gnavus and Clostridium innocuum (AQ) (False Discovery Rate p < 0.05). Several pathways involved in protein biosynthesis were depleted in the AP cohort at all time points.

Conclusions: Gut dysbiosis persisted following AP in children at 3 and 12 months follow-up compared to HC. Microbiome signatures differed in the ARP cohort and those with multiple GI symptoms.

Keywords: acute recurrent pancreatitis; children; microbiome; pediatric pancreatitis.