Omega-3 polyunsaturated fatty acids modulate gut microbiota-derived 18β-glycyrrhetinic acid to alleviate type 1 diabetes mellitus

ABSTRACT:

Background

Omega-3 polyunsaturated fatty acids (PUFAs) are known to protect against type 1 diabetes mellitus (T1DM), but how they act through the gut-islet axis is not fully understood. This study explored how Omega-3 PUFA-influenced gut microbiota and their metabolites help protect pancreatic islets in T1DM.

Methods

We used fecal microbiota transplantation (FMT) to test the effects of Omega-3 PUFA-derived gut microbiota in NOD mice. Immune cell changes in the islets were analyzed using transcriptomics, flow cytometry, and immunohistochemistry. Metabolomics identified key metabolites in serum related to gut microbiota changes. Co-culture experiments examined the role of specific metabolites in macrophage polarization and β-cell function.

Results

Omega-3 PUFA-treated and FMT mice showed reduced islet inflammation and an increased abundance of the Eubacterium coprostanoligenes group. Enhanced M2 macrophage polarization was observed in the islet microenvironment of FMT mice. Among gut microbiota metabolites, 18β-glycyrrhetinic acid (18β-GA) was strongly linked to E. coprostanoligenes and stood out as a key molecule. In co-culture experiments, 18β-GA shifted macrophages to an M2 phenotype, which boosted insulin production and secretion in β-cells.

Conclusions

Omega-3 PUFA-derived gut microbiota and the metabolite 18β-GA play a key role in protecting pancreatic islets in T1DM by modulating macrophage polarization and improving β-cell function. These findings suggest new ways to use gut microbiota for T1DM treatment.

INSTRUMENT(S): Liquid Chromatography MS - alternating - reverse phase

PROVIDER: MTBLS13174 | MetaboLights | 2026-06-13

REPOSITORIES: MetaboLights