Type 2 diabetes mellitus (T2DM) is a common metabolic disorder characterized by insulin resistance and pancreatic β-cell dysfunction. Emerging evidence indicates that gut microbiota dysbiosis may contribute to the development of T2DM. Individuals with T2DM exhibit notable changes in gut microbiota composition, including shifts in the balance between Firmicutes and Bacteroidetes, a reduction in butyrate-producing bacteria, and an increase in opportunistic pathogens. Gut microbiota-derived metabolites—such as short-chain fatty acids, bile acids, and amino acids—have been implicated in the pathogenesis of T2DM, highlighting the critical role of host-microbe interactions. In this overview, we discuss the gut microbiota dysbiosis associated with T2DM and explore the molecular links between microbiota-derived metabolites and the pathogenesis of diseases. Additionally, we explore potential therapeutic strategies, including probiotics and dietary interventions, to modulate the gut microbiota and its metabolites, providing insights for future clinical research and the development of novel treatments for T2DM.

Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), imposes a significant global burden with adverse clinical outcomes and escalating healthcare expenditures. Early identification of biomarkers can facilitate better screening, earlier diagnosis, and the prevention of diabetes. However, current clinical predictors often fail to detect abnormalities during the prediabetic state. Emerging studies have identified specific amino acids as potential biomarkers for predicting the onset and progression of diabetes. Understanding the underlying pathophysiological mechanisms can offer valuable insights into disease prevention and therapeutic interventions. This review provides a comprehensive summary of evidence supporting the use of amino acids and metabolites as clinical biomarkers for insulin resistance and diabetes. We discuss promising combinations of amino acids, including branched-chain amino acids, aromatic amino acids, glycine, asparagine and aspartate, in the prediction of T2DM. Furthermore, we delve into the mechanisms involving various signaling pathways and the metabolism underlying the role of amino acids in disease development. Finally, we highlight the potential of targeting predictive amino acids for preventive and therapeutic interventions, aiming to inspire further clinical investigations and mitigate the progression of T2DM, particularly in the prediabetic stage.

Epidemiological evidence regarding the effect of omega-3 polyunsaturated fatty acid (PUFA) supplementation on inflammatory bowel disease (IBD) is conflicting. Additionally, little evidence exists regarding the effects of specific omega-3 components on IBD risk. We applied two-sample Mendelian randomization (MR) to disentangle the effects of omega-3 PUFAs (including total omega-3, α-linolenic acid, eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA)) on the risk of IBD, Crohn’s disease (CD) and ulcerative colitis (UC). Our findings indicated that genetically predicted increased EPA concentrations were associated with decreased risk of IBD (odds ratio 0.78 (95% CI 0.63–0.98)). This effect was found to be mediated through lower levels of linoleic acid and histidine metabolites. However, we found limited evidence to support the effects of total omega-3, α-linolenic acid, and DHA on the risks of IBD. In the fatty acid desaturase 2 (FADS2) region, robust colocalization evidence was observed, suggesting the primary role of the FADS2 gene in mediating the effects of omega-3 PUFAs on IBD. Therefore, the present MR study highlights EPA as the predominant active component of omega-3 fatty acids in relation to decreased risk of IBD, potentially via its interaction with linoleic acid and histidine metabolites. Additionally, the FADS2 gene likely mediates the effects of omega-3 PUFAs on IBD risk.

Background: Type 2 diabetes mellitus (T2DM), characterized by impaired glucose homeostasis, represents a significant threat to public health. Bile acids (BAs), as key metabolic regulators, play an essential role in glucose metabolism. Recent advances in high-resolution metabolomics have revealed that various BA species are closely linked to T2DM pathogenesis and play a critical role in maintaining glucose homeostasis. Understanding the underlying mechanisms by which BAs modulate glucose metabolism provides valuable insights for the prevention and treatment of T2DM. Methods/Results: This review describes the roles of diverse BA species in regulating glucose metabolism and comprehensively summarizes the relationship of unconjugated and conjugated BAs with T2DM in population studies. Furthermore, we discuss BA-targeted therapeutic approaches for T2DM, highlighting the urgent need for developing tissue-restricted modulators of BA receptors and advancing the clinical translation of novel beneficial BAs. Conclusion: Deeply understanding the role of BAs played in the pathogenesis and progression of T2DM will facilitate the development of potential therapeutic agents.