Engineered probiotic restores GLP-1 signaling to ameliorate fiber-deficiency exacerbated colitis

TL;DR

A probiotic engineered to release a bacterial peptide can boost GLP-1 levels and improve gut health in mice with fiber-deficient diets and colitis.

Contribution

The study introduces a probiotic that modulates GLP-1 signaling to treat colitis independently of dietary fiber.

Findings

Fiber deficiency impairs GLP-1 release and increases colitis susceptibility.

A probiotic engineered to release a microbial peptide restores GLP-1 signaling and gut health in fiber-deprived mice.

GLP-1 receptor activation improves gut barrier integrity, metabolism, and antimicrobial defenses during colitis.

Abstract

Western diets reduced in fiber promote dysbiosis and exacerbate colitis, with short-chain fatty acids (SCFAs) from fiber fermentation known to regulate glucagon-like peptide 1 (GLP-1) secretion. Whether GLP-1 dysregulation directly links diet-induced dysbiosis to colitis severity, and if this pathway can be therapeutically targeted independently of dietary fiber, remains unclear. Here, we show that dextran sulfate sodium (DSS)–induced colitis severity correlates with compensatory GLP-1 increases, while receptor blockade worsens damage, confirming GLP-1’s protective role during colitis. Fiber deficiency impaired L cell function and GLP-1 release, increasing colitis susceptibility. GLP-1 receptor agonist reversed these effects, restoring barrier integrity and accelerating recovery. We engineered a probiotic, releasing a microbial peptide, that locally elevates GLP-1, which normalized gut parameters in fiber-deprived mice and alleviated colitis via GLP-1–dependent mechanisms, including improved metabolism, antimicrobial defenses , and barrier restoration. Our findings mechanistically connect fiber deficiency to colitis through GLP-1 and demonstrate that probiotic-mediated GLP-1 modulation can bypass dietary fiber requirements to maintain gut homeostasis.

Engineered probiotic delivers bacterial peptide that enhances GLP-1 and restores barrier integrity in diet-modulated colitis.

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