Investigating the role of diet-manipulated gut bacteria in pathogenesis of type 2 diabetes mellitus—an in vitro approach

Guraka, A, Lush, M, Zouganelis, G, Waldron, J, Mekapothula, S ORCID: https://orcid.org/0000-0002-3906-842X, Masania, J, Cave, GWV ORCID: https://orcid.org/0000-0002-4167-1332, Conway, ME, Tripathi, G and Kermanizadeh, A, 2026. Investigating the role of diet-manipulated gut bacteria in pathogenesis of type 2 diabetes mellitus—an in vitro approach. Nutrients, 18 (2): 279. ISSN 2072-6643

Preview

Text 2559939_Cave.pdf - Published version Download (4MB) | Preview

Abstract

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.

Item Type:	Journal article
Publication Title:	Nutrients
Creators:	Guraka, A., Lush, M., Zouganelis, G., Waldron, J., Mekapothula, S., Masania, J., Cave, G.W.V., Conway, M.E., Tripathi, G. and Kermanizadeh, A.
Publisher:	MDPI
Date:	14 January 2026
Volume:	18
Number:	2
ISSN:	2072-6643
Identifiers:	Number Type 10.3390/nu18020279 DOI 2559939 Other
Rights:	© 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
Divisions:	Schools > School of Science and Technology
Record created by:	Melissa Cornwell
Date Added:	02 Feb 2026 11:47
Last Modified:	02 Feb 2026 11:47
URI:	https://irep.ntu.ac.uk/id/eprint/55163

Actions (login required)

Edit View

Statistics

Views

Downloads