Gut microbe-derived metabolites may influence key factors in type II diabetes mellitus (T2DM) progression.
The gut microbiome plays a significant role in T2DM pathogenesis by producing metabolites from the host diet.
These metabolites can affect host processes such as fat storage, insulin sensitivity, and hormone release.
Diverse metabolites, including and secondary , interact with host receptors in an endocrine-like manner.
There is potential for these microbe-host interactions to become new therapeutic targets for T2DM.
Understanding the safety and efficacy of drugs that target these interactions is a crucial area for future research.
Simplified
Historically, the focus of type II diabetes mellitus (T2DM) research has been on host metabolism and hormone action. However, emerging evidence suggests that the gut microbiome, commensal microbes that colonize the gastrointestinal tract, also play a significant role in T2DM pathogenesis. Specifically, gut microbes metabolize what is available to them through the host diet to produce small molecule metabolites that can have endocrine-like effects on human cells. In fact, the meta-organismal crosstalk between gut microbe-generated metabolites and host receptor systems may represent an untapped therapeutic target for those at risk for or suffering from T2DM. Recent evidence suggests that gut microbe-derived metabolites can impact host adiposity, insulin resistance, and hormone secretion to collectively impact T2DM progression. Here we review the current evidence that structurally diverse gut microbe-derived metabolites, including , secondary , aromatic metabolites, trimethylamine-N-oxide, polyamines, and N-acyl amides, that can engage with host receptors in an endocrine-like manner to promote host metabolic disturbance associated with T2DM. Although these microbe-host signaling circuits are not as well understood as host hormonal signaling, they hold untapped potential as new druggable targets to improve T2DM complications. Whether drugs that selectively target meta-organismal endocrinology will be safe and efficacious in treating T2DM is a key new question in the field of endocrinology. Here we discuss the opportunities and challenges in targeting the gut microbial endocrine organ for the treatment of diabetes and potentially many other diseases where diet-microbe-host interactions play a contributory role.
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