Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia and insulin resistance. The incidence of T2DM is increasing globally, and a growing body of evidence suggests that gut microbiota dysbiosis may contribute to the development of this disease. Gut microbiota-derived metabolites, including bile acids, lipopolysaccharide, trimethylamine-N-oxide, tryptophan and indole derivatives, and short-chain fatty acids, have been shown to be involved in the pathogenesis of T2DM, playing a key role in the host-microbe crosstalk. This review aims to summarize the molecular links between gut microbiota-derived metabolites and the pathogenesis of T2DM. Additionally, we review the potential therapy and treatments for T2DM using probiotics, prebiotics, fecal microbiota transplantation and other methods to modulate gut microbiota and its metabolites. Clinical trials investigating the role of gut microbiota and its metabolites have been critically discussed. This review highlights that targeting the gut microbiota and its metabolites could be a potential therapeutic strategy for the prevention and treatment of T2DM.

The relationship between fibroblast growth factor 21 (FGF21) and cardiovascular disease has been well established in recent studies. This study aimed to investigate the relationship between FGF21 and left ventricular systolic dysfunction and cardiac death. Two-dimensional echocardiography was used to measure the left ventricular ejection fraction (LVEF) to estimate left ventricular systolic function. The optimal cutoff of FGF21 for identifying left ventricular systolic dysfunction at baseline was analyzed via receiver operating characteristic (ROC) curves. The identification of different serum levels of FGF21 and their association with cardiac death was analyzed via Kaplan–Meier survival curves. Serum FGF21 level was measured by an enzyme-linked immunosorbent assay kit, and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level was determined by a chemiluminescent immunoassay. A total of 253 patients were recruited for this study at baseline. Patients were excluded if they lacked echocardiography or laboratory measurement data, and there were 218 patients enrolled in the final analysis. The average age was 66.32 ± 10.10 years. The optimal cutoff values of FGF21 and NT-pro-BNP for identifying left ventricular systolic dysfunction at baseline were 321.5 pg/mL and 131.3 ng/L, respectively, determined separately via ROC analysis. The areas under the curves were non-significant among FGF21, NT-pro-BNP and FGF21 + NT-pro-BNP as determined by pairwise comparisons. Both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP were independent risk factors for left ventricular systolic dysfunction at baseline (odd ratio (OR) 3.138 [1.037–9.500], P = 0.043, OR 9.207 [2.036–41.643], P = 0.004, separately). Further Kaplan–Meier survival analysis indicated an association between both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP with cardiac death in 5 years [RR 5.000 (1.326–18.861), P = 0.026; RR 9.643 (2.596–35.825), P = 0.009, respectively]. Serum FGF21 level was significantly correlated with left ventricular systolic dysfunction at baseline. Patients with higher serum levels of FGF21 tended to suffer greater risks of cardiac death than patients with lower serum levels of FGF21. The identification of FGF21 and its relationship with left ventricular systolic function and cardiac death were non-inferior to NT-pro-BNP.

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple body systems with heterogeneous clinical manifestations. Since gene expression analyses have been accomplished on diverse types of samples to specify SLE-related genes, single-cohort transcriptomics have not produced reliable results. Using an integrated multi-cohort analysis framework, we analyzed whole blood cells from SLE patients from three transcriptomics cohorts (n=1222) and identified a five-gene signature that distinguished SLE patients from controls. We validated the diagnostic performance of this five-gene signature in six independent validation cohorts (n= 469), with an area under the receiver operating characteristic curve of 0.88 [95% CI 0.7 − 0.96]. This five-gene signature may be associated with the proportion of SLE immune cells, and generalizable across ages and sample types with real diagnostic value for clinical application.