The intestinal microbiome of inflammatory bowel disease across the pediatric age range

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.

KEYWORDS:

• Inflammatory bowel disease
• very early onset inflammatory bowel disease
• gut microbiome
• intestinal microbiome
• pediatrics
• dysbiosis
• microbial maturity

Abbreviations

BC	=	Bray Curtis
HC	=	healthy controls
IBD	=	inflammatory bowel disease
MMI	=	microbiota maturity index
PTI	=	children diagnosed with VEO-IBD but provided samples after age 7
RMMI	=	Relative microbiota maturity index
SD	=	Shannon Diversity index
VEO-IBD	=	very early onset inflammatory bowel disease

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2317932

Additional information

Funding

This work was supported by the National Institutes of Health grants K23 DK119585, R61-HL137063, R01-HL113252, the Penn Center for AIDS Research (P30 AI 045008), the PennCHOP Microbiome Program, the Crohn’s & Colitis Foundation, and a Tobacco Formula grant under the Commonwealth Universal Research Enhancement (C.U.R.E) program (grant number SAP # 4100068710).