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Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction
Torsten P M Scheithauer1,2, Hilde Herrema1, Hongbing Yu3
1Department of (Experimental) Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Gut Microbes
|August 19, 2022
Summary
Bacterial flagellin, more abundant in type 2 diabetes (T2D) patients, triggers inflammation in pancreatic islets. This leads to beta-cell dysfunction, suggesting flagellin as a novel therapeutic target for T2D.
Area of Science:
- Endocrinology
- Microbiology
- Immunology
Background:
- Type 2 diabetes (T2D) is linked to pancreatic beta-cell failure, with the gut microbiota's role unclear.
- Obesity is a significant risk factor for T2D and beta-cell dysfunction.
Purpose of the Study:
- To investigate the causal link between gut microbiota composition and beta-cell dysfunction in T2D.
- To explore the role of flagellin, a bacterial component, in T2D pathogenesis.
Main Methods:
- Analysis of gut microbiota in obese individuals with and without T2D from Dutch cohorts.
- In vitro and in vivo studies using mouse pancreatic islets and obese mice.
- Investigation of flagellin's effect on pancreatic islets via Toll-like receptor 5 (TLR-5) signaling.
Main Results:
- Enterobacteriaceae, a source of flagellin, were more abundant in individuals with T2D.
- Flagellin induced a pro-inflammatory response in pancreatic islets via TLR-5.
- This inflammation impaired beta-cell function, reducing insulin gene expression and affecting insulin processing.
Conclusions:
- Increased systemic flagellin in T2D contributes to beta-cell failure.
- Flagellin-induced islet inflammation represents a novel therapeutic target for T2D.
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