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Disordered Gut Microbiota in Children Who Have Chronic Pancreatitis and Different Functional Gene Mutations
Wei Wang1, Yuan Xiao2, Xinqiong Wang2
1Department of General Surgery and Research Institute of Pancreatic Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Insights
Children with chronic pancreatitis (CCP) show significantly reduced gut microbial diversity. Key probiotic genera are depleted, with specific changes linked to genetic mutations, impacting disease mechanisms.
Area of Science:
- Microbiome research
- Gastroenterology
- Pediatric medicine
Background:
- Chronic pancreatitis (CP) pathogenesis is poorly understood, particularly in children (CCP).
- Gut microbiota and host genetics are implicated, but their interplay in CCP remains unclear.
- External factors are less significant in pediatric cases, highlighting intrinsic mechanisms.
Purpose of the Study:
- To identify key gut microbiota genera in children with chronic pancreatitis (CCP).
- To characterize functional gene mutations associated with CCP.
- To explore the relationship between gut microbiota composition and genetic factors in CCP.
Main Methods:
- 16S rRNA sequencing was employed to analyze gut microbiota composition.
- Comparison between healthy controls and CCP patients, including those with various functional gene mutations.
- Receiver operating characteristic (ROC) curve analysis was used to identify diagnostic microbial signatures.
Main Results:
- CCP exhibited significantly reduced alpha diversity in gut microbiota.
- Abundances of Faecalibacterium, Subdoligranulum, Phascolarctobacterium, Bifidobacterium, Eubacterium, and Collinsella were significantly decreased in CCP (AUC=0.92).
- Functional analysis revealed reduced ribosomal activity and metabolism pathways, with enrichment of phosphotransferase systems; specific genera abundances varied with CFTR, CASR, CTSB, SPINK1, and/or PRSS1 mutations.
Conclusions:
- Children with chronic pancreatitis (CCP) experience a depletion of beneficial gut microbiota.
- Distinct gut microbiota profiles are associated with specific functional gene mutations in CCP patients.
- Understanding these microbial and genetic interactions is crucial for elucidating CCP pathogenesis.
Objectives:
Chronic pancreatitis (CP) is a serious condition whose pathogenic mechanism is unclear. Interactions of host genetic factors with gut microbiota have a role, but little is known, especially in children with CP (CCP), in which the external factors are less important. Our objective was to identify the main gut microbiota genera in CCP and to characterize the functional mutations of these patients.
Methods:
We used 16S rRNA sequencing to compare the gut microbiota of healthy controls with patients who had CCP and different functional gene mutations.
Results:
CCP is characterized by gut microbiota with remarkably reduced alpha diversity. Receiver operating characteristic curve analyses indicated that the abundances of 6 genera-Faecalibacterium, Subdoligranulum, Phascolarctobacterium, Bifidobacterium, Eubacerium, and Collinsella-were significantly decreased in CCP, with an area under curve (AUC) of 0.92 when considering all 6 genera together. Functional analysis of gut microbiota in CCP indicated reduced ribosomal activity, porphyrin and chlorophyll metabolism, starch and sucrose metabolism, and aminoacyl-tRNA biosynthesis, but an enrichment of phosphotransferase system pathways. The abundance of Butyricicoccus was significantly decreased in CCP in the presence of CFTR mutations when combined with mutations in CASR, CTSB, SPINK1, and/or PRSS1. The abundance of Ruminococcaceae was significantly increased in CCP when there were mutations in CASR, CTSB, SPINK1, and/or PRSS1. Patients with CCP but no gene mutations had greater abundances of Veillonella and reduced abundances of Phascolarctobacterium.
Discussion:
CCP is associated with a depletion of probiotic gut microbiota, and CCP patients with different functional gene mutations have different gut microbiota.
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