Microbiota-derived imidazole propionate inhibits type 2 diabetic skin wound healing by targeting SPNS2-mediated S1P transport

Imidazole propionate (ImP) is a recently discovered metabolite of T2DM-related gut microbiota. The effect of ImP on T2DM wound healing has not been studied yet. In this research, the changes of ImP-producing bacteria on the skin are firstly evaluated. 16sRNA sequencing results showed that the abundance of ImP-producing bacteria-Streptococcus in the intestine and skin of T2DM mice is significantly increased. Animal experiments show that ImP can inhibit the process of wound healing and inhibit the formation of blood vessels in the process of wound healing. Molecular mechanism research results show that ImP can inhibit S1P secretion mediated by SPNS2, and inhibit the activation of Rho signaling pathway, thereby affecting the angiogenesis process of HUVEC cells. This work also provides a potential drug HMPA that promotes T2DM wound healing.