Background <p>Infected pancreatic necrosis (IPN) is a major determinant of mortality in acute necrotizing pancreatitis (ANP). Although gut bacterial translocation has been proposed as a key mechanism, direct evidence based on paired profiling of gut and pancreatic necrotic microbiota remains limited. This study aimed to compare microbial signatures across gut and extra-intestinal sites in ANP and to explore whether gut microbiota–based features may help identify IPN.</p> Methods <p>In this prospective observational cohort, 22 consecutive ANP patients undergoing the first minimally invasive intervention were enrolled (IPN, <i>n</i> = 16; sterile pancreatic necrosis [SPN], <i>n</i> = 6). Stool, pancreatic necrotic drainage fluid, peripheral blood, and deep sputum were collected at the first intervention and analyzed using SMRT full-length 16&#xa0;S rRNA gene sequencing. The similarity between the gut microbiota and microbiota of extra-intestinal sites was assessed using shared amplicon sequence variants (ASVs) and beta-diversity distances. A genus-level random forest classifier based on gut microbiota profiles was evaluated using internal nested, stratified k-fold cross-validation.</p> Results <p>Gut microbiota composition differed between IPN and SPN, characterized by enrichment of opportunistic pathogens (e.g., <i>Escherichia coli</i>) and depletion of potentially beneficial bacteria (e.g., <i>Akkermansia muciniphila</i>) in IPN. Both shared-ASV and beta-diversity analyses indicated higher similarity between gut microbiota and microbial signatures detected in pancreatic necrotic drainage fluid, blood, and deep sputum in IPN compared with SPN. In IPN, the proportion of shared ASVs was highest between gut and pancreatic necrotic drainage fluid (29.2%), followed by gut and blood (21.7%), and gut and lung (4.3%). The random forest classifier achieved an area under the receiver operating characteristic curve of 0.91 based on internal cross-validation, indicating potential discriminative ability for IPN.</p> Conclusions <p>IPN was associated with gut dysbiosis and increased similarity between gut microbiota and microbial signatures detected at extra-intestinal sites, most prominently in pancreatic necrotic drainage fluid. A gut microbiota–based classifier showed potential discriminative ability for IPN under internal nested cross-validation, but these exploratory findings require confirmation in larger independent cohorts and further mechanistic investigation.</p>

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The similarity between microbiota of gut and pancreatic necrotic drainage fluid in infected pancreatic necrosis and its potential diagnostic value: a prospective observational cohort study

  • Xin Xu,
  • Cong He,
  • Ling Ding,
  • Yaoyu Zou,
  • Xin Huang,
  • Yupeng Lei,
  • Huifang Xiong,
  • Wenhua He,
  • Liang Xia,
  • Nonghua Lu,
  • Yin Zhu

摘要

Background

Infected pancreatic necrosis (IPN) is a major determinant of mortality in acute necrotizing pancreatitis (ANP). Although gut bacterial translocation has been proposed as a key mechanism, direct evidence based on paired profiling of gut and pancreatic necrotic microbiota remains limited. This study aimed to compare microbial signatures across gut and extra-intestinal sites in ANP and to explore whether gut microbiota–based features may help identify IPN.

Methods

In this prospective observational cohort, 22 consecutive ANP patients undergoing the first minimally invasive intervention were enrolled (IPN, n = 16; sterile pancreatic necrosis [SPN], n = 6). Stool, pancreatic necrotic drainage fluid, peripheral blood, and deep sputum were collected at the first intervention and analyzed using SMRT full-length 16 S rRNA gene sequencing. The similarity between the gut microbiota and microbiota of extra-intestinal sites was assessed using shared amplicon sequence variants (ASVs) and beta-diversity distances. A genus-level random forest classifier based on gut microbiota profiles was evaluated using internal nested, stratified k-fold cross-validation.

Results

Gut microbiota composition differed between IPN and SPN, characterized by enrichment of opportunistic pathogens (e.g., Escherichia coli) and depletion of potentially beneficial bacteria (e.g., Akkermansia muciniphila) in IPN. Both shared-ASV and beta-diversity analyses indicated higher similarity between gut microbiota and microbial signatures detected in pancreatic necrotic drainage fluid, blood, and deep sputum in IPN compared with SPN. In IPN, the proportion of shared ASVs was highest between gut and pancreatic necrotic drainage fluid (29.2%), followed by gut and blood (21.7%), and gut and lung (4.3%). The random forest classifier achieved an area under the receiver operating characteristic curve of 0.91 based on internal cross-validation, indicating potential discriminative ability for IPN.

Conclusions

IPN was associated with gut dysbiosis and increased similarity between gut microbiota and microbial signatures detected at extra-intestinal sites, most prominently in pancreatic necrotic drainage fluid. A gut microbiota–based classifier showed potential discriminative ability for IPN under internal nested cross-validation, but these exploratory findings require confirmation in larger independent cohorts and further mechanistic investigation.