Bile acid profiling as an effective biomarker for staging in pediatric inflammatory bowel disease

ABSTRACT

Rapid and accurate clinical staging of pediatric patients with inflammatory bowel disease (IBD) is crucial to determine the appropriate therapeutic approach. This study aimed to identify effective, convenient biomarkers for staging IBD in pediatric patients. We recruited cohorts of pediatric patients with varying severities of IBD to compare the features of the intestinal microbiota and metabolites between the active and remitting disease stages. Metabolites with potential for staging were targeted for further assessment in both patients and colitis model mice. The performance of these markers was determined using machine learning and was validated in a separate patient cohort. Pediatric patients with IBD exhibited distinct gut microbiota structures at different stages of disease activity. The enterotypes of patients with remitting and active disease were Bacteroides-dominant and Escherichia-Shigella-dominant, respectively. The bile secretion pathway showed the most significant differences between the two stages. Fecal and serum bile acid (BA) levels were strongly related to disease activity in both children and mice. The ratio of primary BAs to secondary BAs in serum was developed as a novel comprehensive index, showing excellent diagnostic performance in stratifying IBD activity (0.84 area under the receiver operating characteristic curve in the primary cohort; 77% accuracy in the validation cohort). In conclusion, we report profound insights into the interactions between the gut microbiota and metabolites in pediatric IBD. Serum BAs have potential as biomarkers for classifying disease activity, and may facilitate the personalization of treatment for IBD.

KEYWORDS:

• Pediatric IBD
• intestinal microbiology
• bile acid
• serum biomarkers
• diagnosis and staging

Acknowledgments

We thank Michelle Kahmeyer-Gabbe, PhD, from Liwen Bianji (Edanz) (www.liwenbianji.cn) for editing the English text of a draft of this manuscript.

Disclosure statement

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

Data availability statement

The sequence dataset generated from this study has been deposited in the NCBI database under BioProject number PRJNA998101 in https://www.ncbi.nlm.nih.gov/bioproject/. The data that support the findings of this study are available from the corresponding author upon reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2323231

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (82172324, 81971993, 82002200, and 82202581).