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Unravelling the role of gut microbiota in acute pancreatitis: integrating Mendelian randomization with a nested
Chang Qu1,2, Jiongdi Lu2, Yongyan Chen3
1Department of General Surgery, Peking University First Hospital, Peking University, Beijing, China.
Background:
Gut microbiota may influence the development of acute pancreatitis (AP), a serious gastrointestinal disease with high morbidity and mortality. This study aimed to identify a causal link by investigating the relationship between gut microbiota and AP.
Methods:
Mendelian randomization (MR) and a nested case-control study were used to explore associations between gut microbiota composition and AP. 16S rRNA sequencing, random forest modelling (RF), support vector machine (SVM), and Kaplan-Meier survival analysis was applied to identify significant gut microbiota and their correlation with hospitalization duration in AP patients.
Results:
Bidirectional MR results confirmed a causal link between specific gut microbiota and AP (15 and 8 microbial taxa identified via forward and reverse MR, respectively). The 16S rRNA sequencing analysis demonstrated a pronounced difference in gut microbiota composition between cases and controls. Notably, after a comprehensive evaluation of the results of RF and SVM, Bacteroides plebeius (B. plebeius) was found to play a significant role in influencing the hospital status. Using a receiver operating characteristic (ROC) curve, the predictive power (0.757) of B. plebeius. Kaplan-Meier survival analysis offered further insight that patients with an elevated abundance of B. plebeius experienced prolonged hospital stays.
Conclusion:
Combining MR with nested case-control studies provided a detailed characterization of interactions between gut microbiota and AP. B. plebeius was identified as a significant contributor, suggesting its role as both a precursor and consequence of AP dynamics. The findings highlight the multifactorial nature of AP and its complex relationship with the gut microbiota. This study lays the groundwork for future therapeutic interventions targeting microbial dynamics in AP treatment.
Insights
This study reveals a causal link between gut microbiota and acute pancreatitis (AP). The bacterium Bacteroides plebeius was identified as a key factor influencing AP development and patient hospitalization duration.
Area of Science:
- Gastroenterology
- Microbiology
- Genetics
Background:
- Acute pancreatitis (AP) is a severe gastrointestinal disease with significant morbidity and mortality.
- The gut microbiota's role in AP development is increasingly recognized.
- Investigating the causal relationship between gut microbiota and AP is crucial for understanding disease pathogenesis.
Purpose of the Study:
- To establish a causal link between gut microbiota composition and acute pancreatitis (AP).
- To identify specific microbial taxa associated with AP development and progression.
- To explore the potential of gut microbiota as therapeutic targets for AP.
Main Methods:
- Employed Mendelian randomization (MR) and nested case-control studies to analyze gut microbiota-AP associations.
- Utilized 16S rRNA sequencing for microbial composition analysis.
- Applied random forest (RF), support vector machine (SVM), and Kaplan-Meier survival analysis to identify key microbes and their clinical impact.
Main Results:
- Bidirectional MR confirmed causal relationships between specific gut microbes and AP.
- Significant differences in gut microbiota composition were observed between AP cases and controls.
- Bacteroides plebeius (B. plebeius) was identified as a crucial factor influencing AP status and predicting prolonged hospitalization.
Conclusions:
- The combined MR and case-control approach elucidated complex gut microbiota-AP interactions.
- Bacteroides plebeius emerges as a significant contributor to AP, potentially acting as both a precursor and consequence.
- Findings support targeting microbial dynamics for future AP therapeutic strategies.
Related Concept Videos
01:27Acute Pancreatitis I: Introduction
Acute pancreatitis is characterized by rapid inflammation of the pancreas, often caused by factors like gallstone blockage or excessive alcohol consumption. Chronic pancreatitis, on the other hand, is a slow, progressive inflammation that may result from long-term alcohol abuse, obstructions in the pancreatic duct, or genetic factors.
The causes of acute pancreatitis include:
01:24Chronic Pancreatitis I: Introduction
Pancreatitis is the inflammation of the pancreas, which occurs when the immune system becomes active and causes swelling, pain, and disruptions in organ function. Pancreatitis can manifest as either an acute or chronic condition.
Acute pancreatitis arises suddenly and lasts for a brief duration, while chronic pancreatitis is a long-term affliction...
01:30Acute Pancreatitis II: Clinical Manifestations and Management
01:29Chronic Pancreatitis II: Collaborative Care
Assessment: