(A) In the direct model certain microbes (such as some strains of Aeromonas, a rod-shaped bacterium shown here in orange) in the lumen of the intestine secrete BefA (orange circles), which then circulates in the blood and stimulates the proliferation of β cells and/or β cell progenitors (P_β) in the pancreas. (B) In the indirect model BefA promotes the differentiation of the intestine or stimulates the cells lining the intestine to release an undefined ‘Factor X’ (black squares), which then circulates in the blood and promotes β cell expansion in the pancreas. The α- and δ-cells in the pancreas are not affected by BefA.