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Local immune response to food antigens drives meal-induced abdominal pain
Nature ( IF 42.778 ) Pub Date : 2021-01-13 , DOI: 10.1038/s41586-020-03118-2
Javier Aguilera-Lizarraga; Morgane V. Florens; Maria Francesca Viola; Piyush Jain; Lisse Decraecker; Iris Appeltans; Maria Cuende-Estevez; Naomi Fabre; Kim Van Beek; Eluisa Perna; Dafne Balemans; Nathalie Stakenborg; Stavroula Theofanous; Goele Bosmans; Stéphanie U. Mondelaers; Gianluca Matteoli; Sales Ibiza Martínez; Cintya Lopez-Lopez; Josue Jaramillo-Polanco; Karel Talavera; Yeranddy A. Alpizar; Thorsten B. Feyerabend; Hans-Reimer Rodewald; Ricard Farre; Frank A. Redegeld; Jiyeon Si; Jeroen Raes; Christine Breynaert; Rik Schrijvers; Cédric Bosteels; Bart N. Lambrecht; Scott D. Boyd; Ramona A. Hoh; Deirdre Cabooter; Maxim Nelis; Patrick Augustijns; Sven Hendrix; Jessica Strid; Raf Bisschops; David E. Reed; Stephen J. Vanner; Alexandre Denadai-Souza; Mira M. Wouters; Guy E. Boeckxstaens

Up to 20% of people worldwide develop gastrointestinal symptoms following a meal1, leading to decreased quality of life, substantial morbidity and high medical costs. Although the interest of both the scientific and lay communities in this issue has increased markedly in recent years, with the worldwide introduction of gluten-free and other diets, the underlying mechanisms of food-induced abdominal complaints remain largely unknown. Here we show that a bacterial infection and bacterial toxins can trigger an immune response that leads to the production of dietary-antigen-specific IgE antibodies in mice, which are limited to the intestine. Following subsequent oral ingestion of the respective dietary antigen, an IgE- and mast-cell-dependent mechanism induced increased visceral pain. This aberrant pain signalling resulted from histamine receptor H1-mediated sensitization of visceral afferents. Moreover, injection of food antigens (gluten, wheat, soy and milk) into the rectosigmoid mucosa of patients with irritable bowel syndrome induced local oedema and mast cell activation. Our results identify and characterize a peripheral mechanism that underlies food-induced abdominal pain, thereby creating new possibilities for the treatment of irritable bowel syndrome and related abdominal pain disorders.



中文翻译:

对食物抗原的局部免疫反应导致进餐引起的腹痛

饭后全球多达20%的人出现胃肠道症状1,导致生活质量下降,高发病率和高昂的医疗费用。尽管近年来,科学界和外行社区对这一问题的兴趣明显增加,但随着世界范围内引入无麸质饮食和其他饮食,引起食物引起的腹部不适的潜在机制仍然未知。在这里,我们显示细菌感染和细菌毒素可以触发免疫反应,导致小鼠中饮食抗原特异性IgE抗体的产生,而这种抗体仅限于肠道。在随后口服各自的饮食抗原后,IgE和肥大细胞依赖性机制引起内脏痛加剧。这种异常的疼痛信号是由组胺受体H 1引起的介导的内脏传入过敏。此外,向肠易激综合症患者的直肠乙状结肠粘膜注射食物抗原(面筋,小麦,大豆和牛奶)会引起局部水肿和肥大细胞活化。我们的研究结果确定并表征了食物诱发性腹痛的基础周围机制,从而为肠易激综合征和相关的腹痛疾病的治疗创造了新的可能性。

更新日期:2021-01-13
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