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The intestinal microbiome of inflammatory bowel disease across the pediatric age range
Máire A Conrad1,2, Kyle Bittinger1,2, Yue Ren3
1Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Insights
The gut microbiome
Area of Science:
- Microbiome research
- Pediatric gastroenterology
- Inflammatory bowel disease (IBD)
Background:
- Dysbiosis is linked to pediatric and adult inflammatory bowel disease (IBD).
- The specific role of the microbiome in very early onset IBD (VEO-IBD) remains under-described.
- Understanding microbial community structure in VEO-IBD is crucial for early diagnosis and treatment.
Purpose of the Study:
- To investigate the impact of age and inflammation on gut microbial community structure in children.
- To compare the microbiome of children with VEO-IBD, pediatric-onset IBD, and healthy controls (HC).
- To analyze longitudinal changes in the microbiome over 8 weeks.
Main Methods:
- Shotgun metagenomic sequencing was employed to analyze fecal samples.
- Participants included children with VEO-IBD, pediatric-onset IBD, and age-matched HC.
- A healthy microbial maturity index was developed and applied to assess gut microbiota development.
Main Results:
- Significant differences in alpha and beta diversity were observed between HC and IBD/VEO-IBD groups.
- Children with pediatric-onset IBD and VEO-IBD exhibited lower microbial maturity compared to HC.
- VEO-IBD patients showed greater microbial heterogeneity at younger ages than pediatric IBD patients.
Conclusions:
- Young age and inflammation independently influence gut microbial community structure in children.
- The impact of age and inflammation is not simply additive in the youngest VEO-IBD patients.
- Microbial community analysis, including maturity index, reveals distinct patterns in VEO-IBD compared to pediatric IBD.
Abstract:
Dysbiosis is associated with pediatric and adult-onset inflammatory bowel disease (IBD), but the role of dysbiosis and the microbiome in very early onset IBD (VEO-IBD) has not yet been described. Here, we aimed to demonstrate the impact of age and inflammation on microbial community structure using shotgun metagenomic sequencing in children with VEO-IBD, pediatric-onset IBD, and age-matched pediatric healthy controls (HC) observed longitudinally over the course of 8 weeks. We found disease-related differences in alpha and beta diversity between HC and children with IBD or VEO-IBD. Using a healthy microbial maturity index modeled from HC across the age range to characterize their gut microbiota, we found that children with pediatric-onset IBD and VEO-IBD had lower maturity than their age-matched HC groups, suggesting a disease effect on the microbial community. In addition, patients with pediatric IBD had significantly lower maturity than those with VEO-IBD, who had more heterogeneity at the youngest ages, highlighting differences in these two cohorts that were not captured in standard comparisons of alpha and beta diversity. These results demonstrate that young age and inflammation independently impact microbial community structure. However, the effect is not additive in the youngest patients, likely because of the heterogeneous and dynamic stool microbiome in this population.
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