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Hirschsprung’s disease may increase the incidence of inflammatory bowel disease through alterations in CA1

Pediatric Research volume 98, pages 1580–1590 (2025)Cite this article

Abstract

Background

The role of Hirschsprung’s disease (HSCR) for the development of inflammatory bowel disease (IBD) and the common pathogenesis of the diseases remains unclear. The objective is to investigate the relationship between HSCR and IBD.

Methods

In our study, the Mendelian randomization approach was employed to analyze the causal relationships. A further search was conducted for differentially expressed genes (DEGs) between disease and control tissues in HSCR and IBD. Subsequently, the potential pathway mechanisms were subjected to an enrichment analysis. Furthermore, the molecular docking was employed to investigate the binding relationship between potential therapeutic targets and drugs.

Results

The results show HSCR have an increased risk of developing IBD (IVW: OR = 1.048, P < 0.05; weighted median: OR = 1.065, P < 0.05). A total of 111 DEGs were identified in IBD, while 471 DEGs were observed in HSCR. CA1 was identified as core gene and exhibited lower expression levels in IBD (P < 0.05). Concomitantly, CA1 exhibited reduced expression levels in inflamed tissues. And the TNF and IL17 signaling pathway were found closely related to CA1 expression.

Conclusion

In total, our study shows HSCR promote the occurrence of IBD and reveals pathogenesis. Our results suggest CA1 may provide novel insight for the treatment of HSCR complicated with IBD.

Impact

  • Individuals with HSCR are at a higher risk of developing IBD (IVW: OR = 1.048, P < 0.05; Weighted median: OR = 1.065, P < 0.05).

  • Patients with IBD exhibited lower expression levels of CA1 (P < 0.05). Furthermore, CA1 expression was found to be lower in inflamed tissues (P < 0.05).

  • CA1 may provide novel insight for the treatment of HSCR complicated with IBD.

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Fig. 1: Results of MR analysis.
Fig. 2: Results of variance analysis and enrichment analysis.
Fig. 3: Comparison of immunization between IBD and control samples.
Fig. 4: Results of variance analysis and enrichment analysis.
Fig. 5: Identification of CA1 as the core genes.
Fig. 6: Results of the analysis of the relationship between CA1 and immunity.
Fig. 7: Results of the molecular docking.

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Data availability

The raw data used in this study were obtained from publicly available data. Details of the specific data sources are described in the “MATERIALS AND METHODS” section. Relevant results are available in the supplementary material. The codes used in this analysis can be obtained by contacting the corresponding author.

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Acknowledgements

We would like to acknowledge the public databases including GEO, IEU, GO, KEGG, GEPIA, STRING, JASPAR, Cmap, Drugbank, DGIdb, ChEMBL and HPA for their contributions to human medicine in which they share vast volumes of data. We are also grateful to the majority of researchers who are willing to publicly upload their experimental data. Thanks to the authors of the R package for their contribution to the advancement of Bioinformatics.

Funding

This work was supported in part by Tianjin Municipal Education Commission Research Plan Project (Natural Science) (2023YXZD12) and Tianjin University “Medicine+” Special Fund, Tianjin Natural Science Foundation (22JCZDJC00230).

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Author notes

  1. These authors contributed equally: Enyang He, Bowen Shi, Miao Jia.

Authors and Affiliations

  1. Tianjin Medical University, Tianjin, China

    Enyang He, Miao Jia, Wenjing Sun, Kaili Chang, Hongyv Jiang, Wei Zhao, Hailan Zhao & Hualei Cui

  2. Graduate School of Tianjin Medical University, Tianjin, China

    Enyang He, Miao Jia, Wenjing Sun, Kaili Chang, Hongyv Jiang, Wei Zhao & Hailan Zhao

  3. Department of General Surgery, Tianjin Children’s Hospital, Tianjin, China

    Bowen Shi, Liang Dong & Hualei Cui

  4. Department of General & Neonatal Surgery, Children’s Hospital of Chongqing Medical University, Chongqing, China

    Xiaohong Die & Wei Feng

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  1. Enyang He
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  2. Bowen Shi
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  3. Miao Jia
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  11. Wei Feng
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Contributions

Research idea and design: Enyang He, Xiaohong Die and Hualei Cui. Data acquisition: Enyang He, Hailan Zhao and WeiZhao. Data analysis: Enyang He, Bowen Shi, Wenjin Sun, Miao Jia and Kaili Chang. Manuscript Writing: Enyang He,WeiFeng, Bowen Shi and Hongyv Jiang. Reviewing: Enyang He, Liang Dong and Hualei Cui.

Corresponding authors

Correspondence to Wei Feng or Hualei Cui.

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The study was based on open-source data from multiple databases. Ethical approval has been provided for the patients involved in these databases. Therefore, there are no ethical issues with this article.

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He, E., Shi, B., Jia, M. et al. Hirschsprung’s disease may increase the incidence of inflammatory bowel disease through alterations in CA1. Pediatr Res 98, 1580–1590 (2025). https://doi.org/10.1038/s41390-025-03938-w

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