Targeting the gut microbiota and its metabolites for type 2 diabetes mellitus

Abstract

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.

Diabetic Rats Induced Using a High-Fat Diet and Low-Dose Streptozotocin Treatment Exhibit Gut Microbiota Dysbiosis and Osteoporotic Bone Pathologies

“…In these scenarios, signaling factors from pathways like the RAGE (receptor for advanced glycation end products)-JAK pathway, NF-κB pathway, and Wnt/β-catenin pathway have been shown to regulate bone homeostasis, making them potential markers for assessing diabetic osteopathogenesis [ 5 , 25 ]. Furthermore, recent evidence has revealed interesting changes in gut microbiota during the progression of DM or bone disease [ 45 , 46 ]. Therefore, investigating the specific gut bacteria that influence the development of diabetic bone disease could be a new approach for developing theragnostic tools or drugs.…”

Advances in fecal microbiota transplantation for the treatment of diabetes mellitus

“…Therefore, DM is associated with enteric dysbacteriosis, which damages the intestinal mucosal barrier and increases intestinal permeability. When the metabolite lipopolysaccharide (LPS) is translocated and released into the blood through a leaky intestinal mucosal barrier, a large amount of endotoxin is produced, which damages the function of islet β-cells, produces immune inflammation, activates macrophages, leads to vascular inflammation, and participates in the occurrence of DM ( Zhang et al., 2021 ; Del Chierico et al., 2022 ; Guo et al., 2022 ; Lin et al., 2022 ; Zhou et al., 2022 ; Crudele et al., 2023 ; Wang et al., 2023 ; Wu et al., 2023 ) ( Figure 3 ).…”

“…Specifically, the number of probiotic colonies, such as Bifidobacterium and Firmicutes , is decreased, and the number of pathogenic bacteria, such as Enterococcus and Enterobacter , is increased, resulting in an increase in inflammatory factors. In addition, these variations can induce the production of LPS, activate inflammatory responses, and affect the metabolism of SCFAs, bile acids, tryptophan, and trimethylamine N-oxide, thus promoting the development of DM ( Fu et al., 2023a ; Wu et al., 2023 ) ( Figures 4A, B ).…”

“…The gut microbiota is the most abundant group of antigen-presenting cells (APCs) ( Adak and Khan, 2019 ), and their imbalance disrupts immunity and homeostasis. By introducing environmental antigens into the gastrointestinal tract, the gut microbiota interferes with the reaction between antigens and the host immune system, resulting in increased intestinal permeability and the development of diabetes ( Del Chierico et al., 2022 ; Guo et al., 2022 ; Zhou et al., 2022 ; Crudele et al., 2023 ; Wu et al., 2023 ).…”

A multi-omics approach to investigate characteristics of gut microbiota and metabolites in hypertension and diabetic nephropathy SPF rat models

“…Changes to the intestinal microbiota caused by microbial species and proportions or metabolites derived from microbes are associated with increased susceptibility to diseases (Gentile and Weir, 2018 ). Intestinal microbiota disorders play important roles in DM (Wu et al, 2023 ), DN (Zhao et al, 2023 ), chronic kidney disease, ESRD (Luo et al, 2023 ), and in DM progression to DN and subsequent ESRD (Mao et al, 2023 ). However, the underlying mechanisms of how intestinal flora affects DN remain uncertain.…”