IL-22 from enteroendocrine cells promotes early-life gut motility in zebrafish through the microbiota
- Soraya Rabahi
- Lucie Maurin
- Emiliano Marachlian
- Fabian Guendel
- Aya Mikdache
- Keinis Quintero-Castillo
- Vincenzo Di Donato
- Jessica Riou-Ramon
- Akshai Janardhana Kurup
- Yazan Salloum
- Gwendoline Gros
- Patricia Diabangouaya
- Camila Garcia-Baudino
- Ignacio Medina-Yáñez
- Pascal Hersen
- Alvaro Banderas
- Jean-Pierre Levraud
- Georges Lutfalla
- Filippo Del Bene
- Carmen G. Feijoo
- Gerard Eberl
- German Sumbre
- Jos Boekhorst
- Sylvia Brugman
- Pedro P. Hernández
2026-04-02
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.