Gut microbiota amplifies butyrates impact on optimal intestinal development in neonatal mice via GPR43 Nfe2l2 ABL1 TLR4 pathway_C6

Butyrate supplementation at HM physiological concentrations significantly promoted intestinal development in neonatal mice. In microbiota-depleted mice, butyrate supplementation still enhanced intestinal motor, jejunal villus height, and upregulated intestinal functional genes, indicating that butyrate retains its beneficial effects even without gut microbiota. However, the presence of an intact gut microbiota further amplified butyrates beneficial effects. Butyrate supplementation notably increased the abundance of Muribaculum, and transplantation experiments with Muribaculum gordoncarteri confirmed its critical role in mediating butyrates effects. Network pharmacology and pathway analyses identified the GPR43 Nfe2l2 ABL1 TLR4 signaling pathway as a key mediator of butyrates action.