Ding Yang,1 Rulan Bai,1 Chengzhong Li,2 Yan Sun,2 Hongyu Jing,1 Zixu Wang,1 Yaoxing Chen,1 Yulan Dong1 

1College of Veterinary Medicine, China Agricultural University, Beijing, People’s Republic of China; 2Department of Horticulture and Landscape Architecture, Jiangsu Agri-Animal Husbandry Vocational College, Taizhou, People’s Republic of China

Correspondence: Yulan Dong, Email ylbcdong@cau.edu.cn

Background: The early childhood period is a critical development stage, and experiencing stress during this time may increase the risk of gastrointestinal disorders, including irritable bowel syndrome (IBS). Neonatal maternal separation (NMS) in rodent models has been shown to cause bowel dysfunctions similar to IBS, and 5-HT is considered to be a key regulator regulating intestinal function, but the precise underlying mechanisms remain unclear.
Results: We established a maternal separation stress mouse model to simulate early-life stress, exploring the expression patterns of 5-HT under chronic stress and its mechanisms affecting gut function. We observed a significant increase in 5-HT expression due to NMS, leading to disruptions in intestinal structure and function. However, inhibiting 5-HT reversed these effects, suggesting its potential as a therapeutic target. Furthermore, our research revealed that excess 5-HT in mice with early life stress increased intestinal neural network density and promoted excitatory motor neuron expression. Mechanistically, 5-HT activated the Wnt signaling pathway through the 5-HT4 receptor, promoting neurogenesis within the intestinal nervous system.
Conclusion: These findings shed light on the intricate changes induced by early life stress in the intestines, confirming the regulatory role of 5-HT in the enteric nervous system and providing potential insights for the development of novel therapies for gastrointestinal disorders.

Keywords: 5-HT, IBS, early-life stress, neurogenesis