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Different Fecal Microbiota in Hirschsprung's Patients With and Without Associated Enterocolitis
Alexis P Arnaud1,2, Ianis Cousin3, Françoise Schmitt4
1Institut NuMeCan, INRAE, INSERM, Univ Rennes, Rennes-Saint-Gilles, France.
Insights
Hirschsprung-associated enterocolitis (HAEC) is linked to gut dysbiosis in infants under two years old. This study found specific bacterial changes in infants with HAEC, suggesting a potential cause for the condition in this age group.
Area of Science:
- Microbiome research
- Pediatric gastroenterology
- Inflammatory bowel disease
Background:
- Hirschsprung's disease (HD) patients face a risk of developing Hirschsprung-associated enterocolitis (HAEC), particularly within the first two years of life.
- The exact cause of HAEC is unknown, but intestinal dysbiosis has been implicated.
- Understanding the fecal bacterial composition in relation to HAEC is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the association between fecal bacterial composition and HAEC in a large cohort of Hirschsprung's disease patients.
- To compare microbiota alterations in HD patients with and without HAEC across different age groups.
- To identify specific bacterial taxa linked to HAEC development.
Main Methods:
- Analysis of fecal microbiota structure in 103 Hirschsprung patients (3 months to 16 years) post-surgery.
- 16S rRNA gene sequencing to compare microbiota composition between HAEC and HD groups.
- Stratification of patients into age groups: 0-2, 2-6, 6-12, and 12-16 years.
Main Results:
- Microbiota richness and diversity increased with age but did not differ between HD and HAEC patients.
- A lower relative abundance of Actinobacteria was observed in HAEC patients under 2 years old.
- Multivariate analysis identified *Flavonifractor plautii*, *Eggerthella lenta*, and *Ruminococcus gnavus* group as positively associated with HAEC in the 0-2 years age group.
Conclusions:
- Hirschsprung-associated enterocolitis is associated with intestinal dysbiosis in infants (0-2 years), but not in older patients.
- These findings may explain the higher incidence of HAEC in infants.
- Targeted interventions focusing on gut microbiota modulation could be beneficial for infants with HD.
Background And Objectives:
Patients with Hirschsprung's disease are at risk of developing Hirschsprung-associated enterocolitis, especially in the first 2 years of life. The pathophysiology of this inflammatory disease remains unclear, and intestinal dysbiosis has been proposed in the last decade. The primary objective of this study was to evaluate in a large cohort if Hirschsprung-associated enterocolitis was associated with alterations of fecal bacterial composition compared with HD without enterocolitis in different age groups.
Methods:
We analyzed the fecal microbiota structure of 103 Hirschsprung patients from 3 months to 16 years of age, all of whom had completed definitive surgery for rectosigmoid Hirschsprung. 16S rRNA gene sequencing allowed us to compare the microbiota composition between Hirschsprung's disease patients with (HAEC group) or without enterocolitis (HD group) in different age groups (0-2, 2-6, 6-12, and 12-16 years).
Results:
Richness and diversity increased with age group but did not differ between HD and HAEC patients, irrespective of the age group. Relative abundance of Actinobacteria was lower in HAEC than in HD patients under 2 years of age (-66%, P = 0.045). Multivariate analysis by linear models (MaAsLin) considering sex, medications, birth mode, breast-feeding, and the Bristol stool scale, as well as surgery parameters, highlighted Flavonifractor plautii and Eggerthella lenta, as well as Ruminococcus gnavus group, as positively associated with Hirschsprung-associated enterocolitis in the 0-2 years age group.
Conclusion:
Hirschsprung-associated enterocolitis was associated with features of intestinal dysbiosis in infants (0-2 years) but not in older patients. This could explain the highest rate of enterocolitis in this age group.
Clinical Trial Registration:
https://clinicaltrials.gov/ct2/show/NCT02857205, MICROPRUNG, NCT02857205, 02/08/2016.
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