Related Experiment Video
Updated: Jul 8, 2025
Microbiota Analysis Using Two-step PCR and Next-generation 16S rRNA Gene Sequencing
Published on: October 15, 2019
Causal link between gut microbiota and four types of pancreatitis: a genetic association and bidirectional Mendelian
Kui Wang1,2, Xianzheng Qin1, Taojing Ran1
1Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Background:
A number of recent observational studies have indicated a correlation between the constitution of gut microbiota and the incidence of pancreatitis. Notwithstanding, observational studies are unreliable for inferring causality because of their susceptibility to confounding, bias, and reverse causality, the causal relationship between specific gut microbiota and pancreatitis is still unclear. Therefore, our study aimed to investigate the causal relationship between gut microbiota and four types of pancreatitis.
Methods:
An investigative undertaking encompassing a genome-wide association study (GWAS) comprising 18,340 participants was undertaken with the aim of discerning genetic instrumental variables that exhibit associations with gut microbiota, The aggregated statistical data pertaining to acute pancreatitis (AP), alcohol-induced AP (AAP), chronic pancreatitis (CP), and alcohol-induced CP (ACP) were acquired from the FinnGen Consortium. The two-sample bidirectional Mendelian randomization (MR) approach was utilized. Utilizing the Inverse-Variance Weighted (IVW) technique as the cornerstone of our primary analysis. The Bonferroni analysis was used to correct for multiple testing, In addition, a number of sensitivity analysis methodologies, comprising the MR-Egger intercept test, the Cochran's Q test, MR polymorphism residual and outlier (MR-PRESSO) test, and the leave-one-out test, were performed to evaluate the robustness of our findings.
Results:
A total of 28 intestinal microflora were ascertained to exhibit significant associations with diverse outcomes of pancreatitis. Among them, Class Melainabacteria (OR = 1.801, 95% CI: 1.288-2.519, p = 0.008) has a strong causality with ACP after the Bonferroni-corrected test, in order to assess potential reverse causation effects, we used four types of pancreatitis as the exposure variable and scrutinized its impact on gut microbiota as the outcome variable, this analysis revealed associations between pancreatitis and 30 distinct types of gut microflora. The implementation of Cochran's Q test revealed a lack of substantial heterogeneity among the various single nucleotide polymorphisms (SNP).
Conclusion:
Our first systematic Mendelian randomization analysis provides evidence that multiple gut microbiota taxa may be causally associated with four types of pancreatitis disease. This discovery may contribute significant biomarkers conducive to the preliminary, non-invasive identification of Pancreatitis. Additionally, it could present viable targets for potential therapeutic interventions in the disease's treatment.
Insights
This study used Mendelian randomization to find causal links between gut bacteria and pancreatitis. Certain gut microbes may cause pancreatitis, offering potential diagnostic and therapeutic targets.
Area of Science:
- Gastroenterology
- Microbiome Research
- Genetic Epidemiology
Background:
- Observational studies suggest a gut microbiota-pancreatitis link, but causality remains unclear due to confounding factors.
- Previous research is limited by potential bias and reverse causality, necessitating robust causal inference methods.
- Understanding the specific gut microbiota's role in pancreatitis is crucial for developing targeted interventions.
Purpose of the Study:
- To investigate the causal relationship between specific gut microbiota and four types of pancreatitis.
- To identify potential gut microbial biomarkers for pancreatitis diagnosis.
- To explore novel therapeutic targets within the gut microbiome for pancreatitis treatment.
Main Methods:
- A two-sample bidirectional Mendelian randomization (MR) study was conducted using genome-wide association study (GWAS) data from 18,340 participants.
- Data for acute pancreatitis (AP), alcohol-induced AP (AAP), chronic pancreatitis (CP), and alcohol-induced CP (ACP) were sourced from the FinnGen Consortium.
- Primary analysis employed the Inverse-Variance Weighted (IVW) method, with Bonferroni correction and sensitivity analyses (MR-Egger, Cochran's Q, MR-PRESSO, leave-one-out) to ensure robustness.
Main Results:
- A total of 28 gut microflora showed significant associations with various pancreatitis outcomes.
- Class Melainabacteria demonstrated a strong causal association with alcohol-induced chronic pancreatitis (ACP) (OR = 1.801, p = 0.008) after Bonferroni correction.
- Reverse causation analysis identified associations between pancreatitis and 30 distinct gut microflora types, with no significant heterogeneity detected in SNPs.
Conclusions:
- This Mendelian randomization study provides evidence for causal links between gut microbiota and pancreatitis.
- Identified gut microbiota may serve as biomarkers for early, non-invasive pancreatitis detection.
- These findings suggest potential therapeutic targets within the gut microbiome for pancreatitis management.
Related Concept Videos
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...
01:11Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
01:29Chronic Pancreatitis II: Collaborative Care
Assessment:
01:17Irritable Bowel Syndrome I: Introduction
IBS is a chronic condition that can persist over a long period or recur frequently.
The pathogenesis of IBS involves a complex interplay of the following factors:
Altered...
01:50What is Monogastric Digestion?
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: