Altered Development of Gut Microbiota and Gastrointestinal Inflammation in Children with Post-Operative

Caitlin E Murphy1, Michael J Coffey1,2, Quinlan Chen1

  • 1School of Clinical Medicine, Discipline of Paediatrics and Child Health, UNSW Medicine and Health, University of New South Wales, Randwick 2052, Australia.

Insights

Children with Hirschsprung's disease (HD) show altered gut microbial development and inflammation trajectories compared to healthy peers, potentially involving Fusobacteria. These gut changes correlate with reduced quality of life in HD patients.

Area of Science:

  • Microbiome Research
  • Pediatric Gastroenterology
  • Inflammation Biology

Background:

  • Persistent gastrointestinal symptoms in Hirschsprung's disease (HD) post-surgery suggest contributing factors beyond surgical correction.
  • Gut dysbiosis is a potential factor, but human studies comparing intestinal microbiota in pediatric HD patients and healthy controls are limited.
  • Animal models indicate both intrinsic HD-related and post-resection gut ecosystem changes.

Purpose of the Study:

  • To compare the intestinal microbiota and inflammatory profiles between post-operative children with HD and healthy children (HCs).
  • To investigate the relationship between gut microbiota development, inflammation, and clinical outcomes in pediatric HD.
  • To explore potential microbial factors, such as Fusobacteria, associated with altered gut function in HD.

Main Methods:

  • Collected dietary surveys, clinical data, and stool samples from 15 post-operative HD children and 15 HCs.
  • Performed 16S rRNA gene sequencing on stool samples to analyze microbiota composition.
  • Quantified fecal calprotectin as a marker of gastrointestinal inflammation and assessed Pediatric Quality of Life (PedsQL) scores.

Main Results:

  • No global microbiota differences were found between HD and HC cohorts, nor between those with or without HD-associated enterocolitis (HAEC).
  • Healthy controls exhibited age-related increases in alpha diversity and decreases in calprotectin, patterns absent in HD patients.
  • Lower alpha diversity correlated with higher fecal calprotectin across the combined cohort. In HD, Fusobacteria abundance positively correlated with calprotectin.

Conclusions:

  • Children with HD exhibit a divergence from healthy developmental trajectories in gut microbial communities and inflammation, potentially involving Fusobacteria.
  • Reduced health-related quality of life in HD patients aligns with ongoing gastrointestinal symptoms, though not directly linked to observed microbial or inflammatory markers.
  • The study highlights altered microbial and inflammatory development in pediatric HD, underscoring the need for further investigation into gut dysbiosis.

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