The role of the gut microbiota and its metabolites: a new predictor in diabetes and its complications

Abstract

Type 2 diabetes (T2D) is easy to trigger many organ or system lesions, which can lead to various metabolic diseases, such as diabetic kidney disease (DKD), diabetic liver disease, diabetic cardiovascular disease, diabetic foot, etc. Due to the easy availability of stool and blood samples from patients, the study of gut microbes and their metabolites are progressing rapidly. The relationship between pathophysiological alterations of metabolic disorders and gut microbiota composition provides new approaches to precisely identify disease dynamics and refine disease treatment strategies. The aim of this review is to investigate the association between T2D with its complications and gut microbiota. Gut microbial metabolites are a new class of signaling molecules, and the mechanisms and pathways of their signal transduction have also been extensively studied. As a result, we will focus on the characteristics of gut microbiota and its metabolites in metabolic diseases as well as the relationship between gut barrier theory and the circulation of gut microbiota-derived metabolites in vivo. In addition, we elucidate the potential applicability of these characterizations and molecular mechanisms in clinical and pharmacological environment, analyzing their feasibility as predictive molecules for health management and clinically accurate predictions in daily life.

Keywords: Gut barrier; Gut microbiota; Gut microbiota metabolites; Health management; Metabolic disorder; T2D.

Fig. 1

Factors affecting gut microbiota architecture in healthy people. A Diet: incorrect diet can change the microbiome architecture. B Life style: bad habits such as sitting for long periods of time and focusing on electronic devices can change the microbiome of healthy people. C Environmental conditions and drug abuse: environmental pollution and the overuse of drugs such as antibiotics disrupt the microbiome of healthy people

Fig. 2

Gut microbiota regulates major targets/mechanisms in the human body through signaling metabolites under metabolic disorders. ➀ Membrane anchored receptors, mainly GPCR, detect the vast majority of microbial metabolites (e.g., SCFAs, bile acids, and indole derivatives) and initiate signal transduction and cellular responses. ➁ Endotoxins, lipid cholic acids and peptidoglycans activate TLR through pathogen-associated molecular patterns (PAMPs) to induce inflammation. ➂ Imidazole propionate is a propionate that impacts insulin signaling by activating p38 MAPK and phosphorylation of p62, resulting in increased mTOR activity. ➃ Certain metabolites, including as propionate, isoalloLCA, and deoxycholic acid, have the ability to alter the dynamic or energetic metabolism of the mitochondria. Created with BioRender.com

Fig. 3

Importance of the three key barriers in maintaining the ecological balance of the intestine for the flow of metabolite signaling molecules and the regulation of the body

Fig. 4

Characterization of gut microbiota and its metabolites as novel biomolecules