Abstract
Mounting evidence suggested that the gut microbiota has a significant role in the metabolism and disease status of the host. In particular, Type 2 Diabetes (T2D), which has a complex etiology that includes obesity and chronic low-grade inflammation, is modulated by the gut microbiota and microbial metabolites. Current literature supports that unbalanced gut microbial composition (dysbiosis) is a risk factor for T2D. In this review, we critically summarize the recent findings regarding the role of gut microbiota in T2D. Beyond these associative studies, we focus on the causal relationship between microbiota and T2D established using fecal microbiota transplantation (FMT) or probiotic supplementation, and the potential underlying mechanisms such as byproducts of microbial metabolism. These microbial metabolites are small molecules that establish communication between microbiota and host cells. We critically summarize the associations between T2D and microbial metabolites such as short-chain fatty acids (SCFAs) and trimethylamine N-Oxide (TMAO). Additionally, we comment on how host genetic architecture and the epigenome influence the microbial composition and thus how the gut microbiota may explain part of the missing heritability of T2D found by GWAS analysis. We also discuss future directions in this field and how approaches such as FMT, prebiotics, and probiotics supplementation are being considered as potential therapeutics for T2D.
Highlights
Diabetes is a metabolic disorder characterized by elevated blood glucose levels
We critically summarize the recent developments describing the role of microbiota on Type 2 Diabetes (T2D) susceptibility, development, and severity
Liraglutide increased the abundance of A. muciniphila, Allobaculum, Anaerostipes, Blautia, Butyricimonas, Desulfovibrio, Lactobacillus, Turicibacter, and short-chain fatty acids (SCFAs) producing bacteria and decreased the abundance of Bacteroidales, Clostridiales, Proteobacteria [132, 133]. These data suggest that the beneficial effect on hyperglycemia these drugs have, may in part be through the gut microbiota, further clinical studies are needed
Summary
Diabetes is a metabolic disorder characterized by elevated blood glucose levels. The incidence of diabetes is widespread and the International Diabetes Federation (IDF) reports that 463 million people in the world are suffering from diabetes, which is estimated to reach 700 million by the year 2045 [1]. Landmark studies in the 2000s [27,28,29] demonstrated that the microbiota contributes to digestion, carbohydrate metabolism, obesity, and plasma glucose levels. Those studies established a causal relationship by showing that the susceptibility to obesity could be transferred between mice when the fecal microbiota of obese mice was transplanted into non-obese animals. Several studies have demonstrated associations between gut microbiota, or microbial components, and low-grade inflammation in T2D [34]. Induction of interleukin (IL)-10 and IL-22 by species of TABLE 1 | T2D-related gut microbiota found in human studies
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