"Envbiotics" -- a novel framework for microbiota-targeted therapeutic strategies in type 2 diabetes mellitus.

Imbalance of the gut microbiota is an important trigger for insulin resistance in type 2 diabetes mellitus(T2DM). Microbiota-targeted therapies have gradually become an emerging research direction for treating T2DM. However, exogenous strain interventions (supplementing probiotics and fecal microbiota transplantation), endogenous optimization of the gut microbiota (supplementing prebiotics, synbiotics, and postbiotics), and phage therapy focus on "directly introducing microorganisms," "feeding microorganisms," or "directly utilizing microbial components." These approaches cannot cover active substances that target the host as the core and regulate the intestinal microenvironment in a non-nutritional manner, presenting conceptual limitations. In this context, this paper proposes the concept of "Envbiotics, " defined as substances that target the host as the core, optimize the intestinal microenvironment through their own or host metabolites, and directly or indirectly regulate the structure and function of the microbiota in a non-nutritional manner, thereby improving host metabolism and health. Typical evidence, including berberine, urolithin A, plant exosomes, and special targeted delivery technologies, is used to elucidate its mechanism of action. Envbiotics not only fill the gaps in the existing classification system but also provide novel insights for the development of new drugs targeting microbial intervention in T2DM.