IL-22 from enteroendocrine cells promotes early-life gut motility in zebrafish through the microbiota

• 成果类型: Article
• 署名作者: Rabahi, Soraya; Maurin, Lucie; Marachlian, Emiliano; Guendel, Fabian; Mikdache, Aya; Quintero-Castillo, Keinis; Di Donato, Vincenzo; Riou-Ramon, Jessica; Kurup, Akshai Janardhana; Salloum, Yazan; Gros, Gwendoline; Diabangouaya, Patricia; Garcia-Baudino, Camila; Medina-Yanez, Ignacio; Hersen, Pascal; Banderas, Alvaro; Levraud, Jean-Pierre; Lutfalla, Georges; Del Bene, Filippo; Feijoo, Carmen G.; Eberl, Gerard; Sumbre, German; Boekhorst, Jos; Brugman, Sylvia; Hernandez, Pedro P.
• 署名单位: Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); UNICANCER; Universite PSL; CNRS - National Institute for Biology (INSB); Institut Curie; Universite PSL; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); Ecole Normale Superieure (ENS); Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Pasteur Network; Institut Pasteur Paris; Universidad Andres Bello; Universidad Andres Bello; Universidad Andres Bello; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); UNICANCER; Sorbonne Universite; Universite PSL; CNRS - Institute of Chemistry (INC); Institut Curie; Leibniz Association; Leibniz Institut fur Neue Materialien (INM); Universite Paris Cite; Pasteur Network; Universite Paris Saclay; Institut Pasteur Paris; Universite de Montpellier; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); Animal Sciences Group of Wageningen UR; Wageningen University & Research; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris-Est-Creteil-Val-de-Marne (UPEC)
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adr1707
• 发表日期: 2026-04-02
• 页码: 69-76
• 关键词: aryl-hydrocarbon receptor; TRYPTOPHAN CATABOLITES; innate; secretion; immunity; GROWTH; stat3

摘要

The gut microbiota, immune system, and enteric nervous system interact to regulate adult gut physiology. However, the mechanisms establishing gut physiology during development remain unknown. We report that in developing zebrafish, enteroendocrine cells produced interleukin-22 (IL-22) in response to microbial signals before lymphocytes populated the gut. In larvae, IL-22 shaped the gut microbiota, increasing Lactobacillaceae abundance and ghrelin expression to promote gut motility. Impaired motility and ghrelin expression were restored in il22-/- zebrafish by transfer of microbiota from wild-type zebrafish or by introducing only Lactobacillus plantarum. IL-22-deficient mice also had impaired gut motility and reduced ghrelin expression in early life, indicating a conserved function. Thus, before immune system maturation, enteroendocrine cells regulate early-life gut function by controlling the microbiota through IL-22.