Stimulation of motilin secretion by bile, free fatty acids, and acidification in human duodenal organoids

•Mechanisms of motilin secretion were assessed in a new human duodenal organoid model.•RNA sequencing identified ion channels and receptors involved in M-cell activity.•M-cells fired action potentials similar to those in other enteroendocrine cell types.•Motilin release was triggered by low pH, bile, and free fatty acid receptor-1 ligands.•Low pH depolarized M-cells and increased calcium through acid-sensing ion channels (ASIC).