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Preparing a Mice Model of Severe Acute Pancreatitis via a Combination of Caerulein and Lipopolysaccharide Intraperitoneal Injection
Published on: May 10, 2024
Gut microbiota predicts severity and reveals novel metabolic signatures in acute pancreatitis
Christoph Ammer-Herrmenau1, Kai L Antweiler2, Thomas Asendorf2
1Department of Gastroenterology, gastrointestinal Oncology and Endocrinology, University Medical Centre Goettingen, Goettingen, Germany.
Objective:
Early disease prediction is challenging in acute pancreatitis (AP). Here, we prospectively investigate whether the microbiome predicts severity of AP (Pancreatitis-Microbiome As Predictor of Severity; P-MAPS) early at hospital admission.
Design:
Buccal and rectal microbial swabs were collected from 424 patients with AP within 72 hours of hospital admission in 15 European centres. 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 (RAC). Secondary endpoints were mortality, length of hospital stay and severity (organ failure >48 hours and/or occurrence of pancreatic collections requiring intervention) as post hoc analysis. Multivariate analysis was conducted from normalised microbial and corresponding clinical data to build classifiers for predicting severity. For functional profiling, gene set enrichment analysis (GSEA) was performed and normalised enrichment scores calculated.
Results:
After data processing, 411 buccal and 391 rectal samples were analysed. The intestinal microbiome significantly differed for the RAC (Bray-Curtis, p value=0.009), mortality (Bray-Curtis, p value 0.006), length of hospital stay (Bray-Curtis, p=0.009) and severity (Bray-Curtis, p value=0.008). A classifier for severity with 16 different species and systemic inflammatory response syndrome achieved an area under the receiving operating characteristic (AUROC) of 85%, a positive predictive value of 67% and a negative predictive value of 94% outperforming established severity scores. GSEA revealed functional pathway units suggesting elevated short-chain fatty acid (SCFA) production in severe AP.
Conclusions:
The orointestinal microbiome predicts clinical hallmark features of AP, and SCFAs may be used for future diagnostic and therapeutic concepts.
Trial Registration Number:
NCT04777812.
Insights
The orointestinal microbiome can predict acute pancreatitis severity, mortality, and hospital stay. Short-chain fatty acids may offer future diagnostic and therapeutic strategies for this condition.
Area of Science:
- Microbiome research
- Gastroenterology
- Clinical diagnostics
Background:
- Early prediction of acute pancreatitis (AP) severity remains a clinical challenge.
- The role of the orointestinal microbiome in AP progression is not fully understood.
Purpose of the Study:
- To prospectively investigate the predictive capacity of the orointestinal microbiome for AP severity at hospital admission.
- To establish a microbiome-based classifier for predicting AP severity and outcomes.
Main Methods:
- Collected buccal and rectal swabs from 424 AP patients within 72 hours of admission across 15 European centers.
- Utilized full-length 16S rRNA and metagenomic sequencing (Oxford Nanopore Technologies).
- Performed multivariate analysis and gene set enrichment analysis (GSEA) to build predictive classifiers and identify functional pathways.
Main Results:
- The intestinal microbiome composition significantly correlated with AP severity, mortality, and hospital stay (p<0.01).
- A microbiome-based classifier achieved an 85% AUROC for predicting severity, outperforming existing scores.
- GSEA indicated elevated short-chain fatty acid (SCFA) production in severe AP cases.
Conclusions:
- The orointestinal microbiome serves as a significant predictor of clinical outcomes in acute pancreatitis.
- SCFAs represent a potential target for future diagnostic and therapeutic interventions in AP management.
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