Microbial Networks and Immunometabolic Dysfunction in Diabetes: A Narrative Review

Abstract

Diabetes mellitus is a polyetiological disease with genetic predisposition and environmental factors, lifestyle, immune dysfunction and tissue specific metabolic disturbance playing a role. While hyperglycaemia and insulin resistance are hallmarks of diabetes, there is increased evidence that the microbial ecosystem plays a role in disease development and progression by interacting with host metabolism and immunity. Oral cavity, gastrointestinal tract and the interconnection of oral, gut and metabolic axes are important microbial interfaces between environmental factors and systemic metabolic regulation. This review addresses the emerging concept of microbial dysbiosis, epithelial barrier dysfunction, microbial metabolites, and immune activation in diabetics. Changes in oral and gut microbial communities can both lead to increased systemic inflammatory burden via periodontal inflammation and microbial component release, or by changes to intestinal permeability, endotoxin exposure, production of short-chain fatty acids, and bile acid metabolism. These processes may include, among many others, the impact on insulin sensitivity and β-cell function, as well as on the integrity of the vessels and on chronic inflammatory signalling. We will talk about evidence associating alterations in microbes with diabetes-associated metabolic dysfunction, and differentiate between known mechanisms from emerging hypotheses. We also discuss therapeutic potential related to diet manipulation, probiotics, prebiotics, and microbiome targeting, along with current challenges and the necessity for mechanistic validation. A holistic perspective of the oral–gut–metabolic axis may help to better understand diabetes as an environmentally triggered immunometabolic disease and could guide future prevention, risk stratification and targeted intervention.