Early life stress induces irritable bowel syndrome from childhood to adulthood in mice

Enfu Tao; Yuhao Wu; Chenmin Hu; Zhenya Zhu; Diya Ye; Gao Long; Bo Chen; Rui Guo; Xiaoli Shu; Wei Zheng; Ting Zhang; Xinyi Jia; Xiao Du; Marong Fang; Mizu Jiang

doi:10.3389/fmicb.2023.1255525

Early life stress induces irritable bowel syndrome from childhood to adulthood in mice

Front Microbiol. 2023 Oct 2:14:1255525. doi: 10.3389/fmicb.2023.1255525. eCollection 2023.

Authors

Enfu Tao^{1

2}, Yuhao Wu¹, Chenmin Hu¹, Zhenya Zhu¹, Diya Ye¹, Gao Long¹, Bo Chen¹, Rui Guo¹, Xiaoli Shu¹, Wei Zheng^{1

3}, Ting Zhang¹, Xinyi Jia^{1

3}, Xiao Du^{1

3}, Marong Fang⁴, Mizu Jiang^{1

3}

Affiliations

¹ Pediatric Endoscopy Center and Gastrointestinal Laboratory, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, China.
² Department of Neonatology and NICU, Wenling Maternal and Child Health Care Hospital, Wenling, China.
³ Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, China.
⁴ Institute of Neuroscience and Gastrointestinal Laboratory, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Abstract

Background: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorder. Traditionally, early life stress (ELS) is predisposed to IBS in adult. However, whether ELS induces IBS in early life remains unclear.

Methods: Separated cohort studies were conducted in neonatal male pups of C57BL/6 mice by maternal separation (MS) model. MS and non-separation mice were scheduled to be evaluated for prime IBS-phenotypes, including visceral hypersensitivity, intestinal motility, intestinal permeability, and anxiety-like behavior. Ileal contents and fecal samples were collected and analyzed by 16S rRNA gene sequencing and bacterial community analyses. Subcellular structures of intestinal epithelial, such as epithelial tight junctions and mitochondria, were observed under transmission electron microscopy.

Results: MS induced visceral hypersensitivity and decreased total intestinal transit time from childhood to adulthood. In addition, MS induced intestinal hyperpermeability and anxiety-like behavior from adolescence to adulthood. Besides, MS affected intestinal microbial composition from childhood to adulthood. Moreover, MS disrupted intestinal mitochondrial structure from childhood to adulthood.

Conclusion: The study showed for the first time that MS induced IBS from early life to adulthood in mice. The disrupted intestinal mitochondrial structure and the significant dysbiosis of intestinal microbiota in early life may contribute to the initiation and progress of IBS from early life to adulthood.

Keywords: brain-gut-microbiota axis; early life stress; irritable bowel syndrome; maternal separation; visceral hypersensitivity.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by a project from the National Clinical Research Center for Child Health (G20A0008Z).