Disordered Gut Microbiota in Children Who Have Chronic Pancreatitis and Different Functional Gene Mutations

Clin Transl Gastroenterol. 2020 Mar;11(3):e00150. doi: 10.14309/ctg.0000000000000150.

Abstract

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.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Computational Biology
  • DNA Mutational Analysis
  • DNA, Bacterial / isolation & purification
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome / physiology*
  • Genetic Predisposition to Disease*
  • Host Microbial Interactions / genetics*
  • Humans
  • Male
  • Mutation
  • Pancreatitis, Chronic / genetics*
  • Pancreatitis, Chronic / microbiology
  • RNA, Ribosomal, 16S / genetics

Substances

  • DNA, Bacterial
  • RNA, Ribosomal, 16S