Pancreatitis - Microbiome As Predictor of Severity P-MAPS

Objective: Early prediction of the disease course is challenging in acute pancreatitis (AP). Here, we investigate whether the orointestinal microbiome affects the course of disease in AP early at admission. Design: Buccal and rectal microbial swabs were collected from 424 AP patients within 72h of hospital admission in 15 European centers. All samples were sequenced by full-length 16S rRNA and metagenomic sequencing using Oxford Nanopore Technologies. Primary endpoint was the association of the orointestinal microbiome with the revised Atlanta classification. Secondary endpoints were mortality, length of hospital stay, and severity (organ failure > 48h and/or occurrence of pancreatic collections requiring intervention) as post-hoc analysis. Multivariate analysis was conducted from normalized microbial and corresponding clinical data to build classifiers for predicting severity. For functional metabolic profiling gene set enrichment analysis (GSEA) was performed and normalized enrichment scores calculated. Results: 411 buccal and 391 rectal samples were analyzed. The intestinal microbiome significantly differed for the revised Atlanta classification (Bray-Curtis, p-value = 0.009), mortality (Bray-Curtis, p-value 0.006), length of hospital stay (Bray-Curtis, p= 0.009) and severe vs. non-severe (Bray-Curtis, p-value = 0.008). A classifier for severity with 13 different species and SIRS achieved an AUROC of 85.0%, a positive predictive value of 66.6%, and a negative predictive value of 94% outperforming established severity scores. GSE revealed functional pathway modules suggesting elevated short-chain fatty acids (SCFA) production in severe AP. Conclusions: The orointestinal microbiome predicts clinical hallmark features of AP, and SCFAs may be utilized for future diagnostic and therapeutic concepts.