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Investigating the Role of Diet-Manipulated Gut Bacteria in Pathogenesis of Type 2 Diabetes Mellitus—An In Vitro Approach

Title: Investigating the Role of Diet-Manipulated Gut Bacteria in Pathogenesis of Type 2 Diabetes Mellitus—An In Vitro Approach
Authors: Asha Guraka; Marie Lush; Georgios Zouganelis; Joe Waldron; Subbareddy Mekapothula; Jinit Masania; Gareth Wynn Vaughan Cave; Myra Elizabeth Conway; Gyanendra Tripathi; Ali Kermanizadeh
Source: Nutrients ; Volume 18 ; Issue 2 ; Pages: 279
Publisher Information: Multidisciplinary Digital Publishing Institute
Publication Year: 2026
Collection: MDPI Open Access Publishing
Subject Terms: gut microbiome; type 2 diabetes mellitus; in vitro approach; Bacteriodes thetaiotaomicron; Lactobacillus fermentum; diet; short-chain fatty acids
Subject Geographic: agris
Description: Background: The human gut microbiome is highly complex, and its composition is strongly influenced by dietary patterns. Alterations in microbiome structure have been associated with a range of diseases, including type 2 diabetes mellitus. However, the underlying mechanisms for this remain poorly understood. In this study, a novel in vitro approach was utilized to investigate the interplay between gut bacteria, dietary metabolites, and metabolic dysfunction. Methods: Two representative gut bacterial species—Bacteroides thetaiotaomicron and Lactobacillus fermentum—were isolated from human faecal samples and subjected to controlled dietary manipulation to mimic eubiotic and dysbiotic conditions. Metabolites produced under these conditions were extracted, characterized, and quantified. To assess the functional impact of these metabolites, we utilized the INS-1 832/3 insulinoma cell line, evaluating insulin sensitivity through glucose-stimulated insulin secretion and ERK1/2 activation. Results: Our findings demonstrate that metabolites derived from high-carbohydrate/high-fat diets exacerbate metabolic dysfunction, whereas those generated under high-fibre conditions significantly enhance insulin secretion and glucose-dependent ERK1/2 activation in co-culture compared to monocultures. Conclusions: This work systematically disentangles the complex interactions between gut microbiota, diet, and disease, providing mechanistic insights into how microbial metabolites contribute to the onset of metabolic disorders.
Document Type: text
File Description: application/pdf
Language: English
Relation: Nutrition and Public Health; https://dx.doi.org/10.3390/nu18020279
DOI: 10.3390/nu18020279
Availability: https://doi.org/10.3390/nu18020279
Rights: https://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.71793183
Database: BASE