Probiotics as modulators of the gut-derived incretin peptide axis in type 2 diabetes: GLP-1, GLP-2, and microbial metabolite signaling.

Abstract

This review aims to examine the role of probiotics in modulating the gut-derived incretin peptide axis in type 2 diabetes (T2D), with emphasis on GLP-1, related gut peptides such as GLP-2, microbial metabolite signaling, and both conventional and engineered probiotic approaches. Narrative synthesis of literature from PubMed, Scopus, and Google Scholar, using search terms such as 'probiotics', 'GLP-1', 'type 2 diabetes', and 'gut microbiota'. Recent literature from 2015 to 2025 was prioritized, including randomized controlled trials, meta-analyses, systematic reviews, and relevant preclinical studies. Earlier landmark studies were included only when they established foundational mechanisms related to incretin biology, SCFA-FFAR signaling, or GLP-1 secretion physiology. Probiotics promote GLP-1 secretion via SCFAs binding to FFAR2/3 receptors, leading to improved glycemic control in meta-analyses, though with heterogeneity. Engineered probiotics like LgsGPA show superior preclinical efficacy in alleviating hyperglycemia and restoring β-cell function. While conventional probiotics offer benefits, engineered systems represent a promising advancement, requiring further clinical and regulatory development for personalized T2D therapy.