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Murine Ileocolic Bowel Resection with Primary Anastomosis
Published on: October 29, 2014
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.
Abstract:
Gastrointestinal symptoms often persist in children with Hirschsprung's disease (HD) even after "corrective" pull-through surgery. Alteration of the gut microbiota ("dysbiosis") has emerged as a potential contributing factor. Animal studies show gut ecosystem changes that are both intrinsic to HD and caused by bowel resection itself, but human studies comparing the intestinal microbiota of children with HD and healthy children are limited. We collected food frequency dietary surveys, clinical and symptom data, and stool samples from 15 post-operative children with HD and 15 healthy controls (HCs). We performed 16S rRNA gene sequencing from the stool samples and quantified faecal calprotectin as a measure of gastrointestinal inflammation. Despite no global changes in the microbiota between HD and HC cohorts and no differences between individuals with and without a history of HD-associated enterocolitis (HAEC), we identified evidence of altered microbiota development and inflammatory trajectories in HD. In HCs, alpha diversity increased with age (r = 0.83, p < 0.001), while calprotectin levels declined (Spearman's ρ = -0.53, p = 0.04). These age-related patterns were absent in HD. Across the combined cohort, lower alpha diversity was associated with higher faecal calprotectin (Spearman's ρ = -0.47, p = 0.01). In HD, Fusobacteria abundance showed a strong positive correlation with calprotectin (Spearman's ρ = 0.76, adjusted p = 0.02). Pediatric Quality of Life (PedsQL) and gastrointestinal disease-specific symptom scores were lower in HD compared to HC but were not directly linked to microbial diversity or inflammation. Overall, we observed a divergence from healthy peers in the typical developmental trajectory of gut microbial communities and inflammation in children with HD that may involve Fusobacteria. Children with HD reported reduced health-related quality of life compared with HC, consistent with ongoing gastrointestinal symptoms. No microbiota differences were associated with HAEC history, though this may reflect limited sample size.
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