The Role of Gut Microbiota-Derived Metabolites in Modulating Pancreatic β-Cell Senescence: Implications for Type 2 Diabetes Progression                                       

Kibibi Muthoni L.

Faculty of Science and Technology Kampala International University Uganda

ABSTRACT

Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder characterized by insulin resistance and β-cell dysfunction, with emerging evidence highlighting the role of gut microbiota-derived metabolites in modulating pancreatic β-cell senescence. Gut microbiota generates bioactive compounds, including short-chain fatty acids (SCFAs), bile acid derivatives, and amino acid metabolites, which influence β-cell fate through metabolic, inflammatory, and epigenetic pathways. SCFAs, particularly butyrate, exhibit protective effects by enhancing insulin secretion, reducing oxidative stress, and modulating inflammatory responses. Bile acids, through interactions with nuclear receptors such as FXR and TGR5, regulate glucose metabolism and β-cell function. Conversely, dysbiosis-driven shifts in microbial metabolites, including an excess of branched-chain amino acids (BCAAs) and endotoxins like lipopolysaccharides (LPS), exacerbate β-cell senescence via chronic inflammation and mitochondrial dysfunction. This review employed a narrative synthesis methodology, analyzing current literature on microbiota-derived metabolites and their role in β-cell aging. Understanding these interactions provides critical insights into microbiome-based therapeutic strategies for preserving β-cell function and mitigating T2DM progression. Targeted interventions, including probiotics, prebiotics, and dietary modifications, hold promises for modulating gut microbiota composition to enhance metabolic health. Future research should further elucidate microbial metabolite pathways to inform innovative therapeutic approaches aimed at delaying β-cell senescence and T2DM progression.

Keywords: Gut Microbiota-Derived Metabolites, Pancreatic β-Cell Senescence, Type 2 Diabetes Mellitus (T2DM), Short-Chain Fatty Acids (SCFAs), Microbiome-Based Therapeutics.

CITE AS: Kibibi Muthoni L. (2025). The Role of Gut Microbiota-Derived Metabolites in Modulating Pancreatic β-Cell Senescence: Implications for Type 2 Diabetes Progression. RESEARCH INVENTION JOURNAL OF SCIENTIFIC AND EXPERIMENTAL SCIENCES 5(2):101-104. https://doi.org/10.59298/RIJSES/2025/52101104