Wang Shan, Huang Jiahao, He Fangping, He Huiru, Lin Jiaxiao, Zhang Na, He Ying, Tao Ailin
Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Pediatrics, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Pediatr Res. 2025 Jul 25. doi: 10.1038/s41390-025-04222-7.
Functional constipation is the most common diagnosis of gastrointestinal disease in pediatric clinics. Food allergy has been shown to be associated with functional constipation in children. However, the causal relationship has not been well established.
We observed food allergy-like intestinal immune responses and decreased intestinal motility in a mouse model that mimics the atopic march. Consequently, we utilized this model to investigate the role and regulatory mechanisms of the atopic march-induced food allergy on intestinal motility. Pathological features related to weakened intestinal motility were analyzed by RNA sequencing and metabolomics analyses. The role of metabolite deficiency on atopic march-induced constipation in mice was confirmed by supplementation in vivo.
Elevated Th2/Th17 inflammation and decreased serotonin level were found in intestine of atopic march mice. Serotonin synthesis in enterochromaffin cells and enteric serotonergic neurons was found to be impaired. Clinical evidence further supports a reduction in serum serotonin in atopic dermatitis children with food allergies. Based on altered microbiota and disordered lipid metabolism, we identified insufficient isovaleric acid generation contributing to impaired serotonin synthesis in model mice. Isovaleric acid supplementation repaired serotonin synthesis in enteric serotonergic neurons and partially restored intestinal motility of atopic march-induced food allergy mouse model.
Our study provided evidence for the regulatory mechanism of constipation related to atopic march-induced food allergy and suggested targets for its diagnosis and treatment.
The atopic march murine model induces a food allergy-like intestinal immune response, characterized by diminished gastrointestinal motility. Enterogenic serotonin synthesis was impaired in atopic march model mice. Isovaleric acid supplementation repaired serotonin synthesis of enteric serotonergic neurons and restored intestinal motility of atopic march model mice.
功能性便秘是儿科门诊最常见的胃肠道疾病诊断。食物过敏已被证明与儿童功能性便秘有关。然而，因果关系尚未完全确立。
我们在一个模拟特应性进程的小鼠模型中观察到食物过敏样肠道免疫反应和肠道动力下降。因此，我们利用这个模型来研究特应性进程诱导的食物过敏对肠道动力的作用和调节机制。通过RNA测序和代谢组学分析来分析与肠道动力减弱相关的病理特征。通过体内补充来证实代谢物缺乏对小鼠特应性进程诱导的便秘的作用。
在特应性进程小鼠的肠道中发现Th2/Th17炎症升高和血清素水平降低。发现肠嗜铬细胞和肠道血清素能神经元中的血清素合成受损。临床证据进一步支持患有食物过敏的特应性皮炎儿童血清血清素减少。基于微生物群改变和脂质代谢紊乱，我们确定异戊酸生成不足导致模型小鼠血清素合成受损。补充异戊酸可修复肠道血清素能神经元中的血清素合成，并部分恢复特应性进程诱导的食物过敏小鼠模型的肠道动力。
我们的研究为特应性进程诱导的食物过敏相关便秘的调节机制提供了证据，并提出了其诊断和治疗的靶点。
特应性进程小鼠模型诱导了一种食物过敏样肠道免疫反应，其特征是胃肠动力减弱。特应性进程模型小鼠的肠源性血清素合成受损。补充异戊酸可修复肠道血清素能神经元的血清素合成，并恢复特应性进程模型小鼠的肠道动力。
