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Identification of robust associations between admission microbiome profiles and complications of acute pancreatitis
Hannah S Pauw1,2, Hester C Timmerhuis2,3, Marc Besselink4,5
1Surgery, St Antonius Hospital, Nieuwegein, Utrecht, The Netherlands.
Objective:
Patients with acute pancreatitis show reduced gut microbiome diversity and high abundance of pathogenic bacteria compared with healthy subjects. Admission microbiome profiles are increasingly linked to severity, but methodology and study quality hamper interpretation. Our aim was to investigate whether admission microbiome analysis provides robust and reproducible associations with severity and complications of acute pancreatitis.
Methods:
Patients with acute pancreatitis were prospectively enrolled from 20 Dutch hospitals (2019-2022). Admission saliva and rectal samples from 276 patients underwent 16S rDNA sequencing for microbiome profiling. Subgroups were defined based on a literature search. The microbiota endpoints (alpha- and beta-diversity, and genus abundance) were compared across subgroups and with previous studies. Robustness of the significant associations was classified as 'moderate' or 'high' in case of statistical significance in, respectively, 2 or ≥3 differential abundance models.
Results:
Rectal alpha diversity (Shannon Index 3.55 vs 3.63, p=0.026) was decreased in necrotising (n=49) versus oedematous pancreatitis (n=218). Microbiota communities of either saliva or rectal samples differed in all the subgroups. In total, 270 (rectal) and 138 (saliva) genera were associated with severity or complications, of which 35 and 3 (Anaeroglobus and Finegoldia in saliva; Lachnospiraceae_FE2018_group in rectal) were classified as, respectively, moderately and highly robust. Fourteen associations were previously reported, of which 10 were in the opposite direction compared with this study.
Conclusion:
Three admission microbiome taxa associated with severity and complications were highly robust, although their biological relevance remains unclear. This study also shows the lack of replicable findings of admission microbiome associations, highlighting the need for longitudinal studies to establish temporal relationships between microbiome changes and disease progression.
Insights
Admission microbiome analysis in acute pancreatitis shows limited reproducibility. While three gut bacteria taxa showed robust associations with disease severity, most findings lacked consistency, emphasizing the need for longitudinal studies.
Area of Science:
- Gastroenterology
- Microbiome Research
- Clinical Diagnostics
Background:
- Patients with acute pancreatitis exhibit altered gut microbiome diversity and increased pathogenic bacteria.
- Admission microbiome profiles are potential indicators of disease severity but require methodologically sound validation.
- Previous studies on acute pancreatitis microbiome lack consistent findings, hindering reliable interpretation.
Purpose of the Study:
- To assess the robustness and reproducibility of associations between admission microbiome profiles and acute pancreatitis severity.
- To identify specific microbial taxa in saliva and rectal samples linked to pancreatitis severity and complications.
- To compare findings with existing literature and evaluate the reliability of microbiome analysis in this context.
Main Methods:
- Prospective enrollment of 276 acute pancreatitis patients across 20 Dutch hospitals (2019-2022).
- 16S rDNA sequencing of admission saliva and rectal samples for microbiome profiling.
- Statistical analysis of microbial diversity and genus abundance, classifying association robustness across differential abundance models.
Main Results:
- Decreased rectal alpha diversity observed in necrotising pancreatitis compared to oedematous pancreatitis.
- Microbiota composition differed significantly in saliva and rectal samples across patient subgroups.
- Three microbial genera (Anaeroglobus, Finegoldia, Lachnospiraceae_FE2018_group) showed highly robust associations with severity, though biological relevance is undetermined.
Conclusions:
- Admission microbiome analysis identified highly robust taxa associated with acute pancreatitis severity, but their clinical significance requires further investigation.
- The study highlights a lack of reproducible findings in current acute pancreatitis microbiome research.
- Longitudinal studies are crucial to establish causal relationships and understand microbiome dynamics during disease progression.
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