Porphyromonas gingivalis-induced glucose intolerance during periapical lesions requires its LPS throught a Th17 immune response

TL;DR

This study shows that Porphyromonas gingivalis lipopolysaccharides worsen glucose intolerance and bone damage through a Th17 immune response, suggesting IL-17 could be a treatment target.

Contribution

The study identifies IL-17 as a key mediator linking Pg-induced periapical lesions to metabolic dysfunction and glucose intolerance.

Findings

Pg LPS significantly worsened bone lysis and Th17 cell recruitment in wild-type mice.

IL-17 knockout mice showed reduced bone loss and glucose intolerance despite dysbiosis.

Targeting IL-17 could improve glycemic control in periapical disease.

Abstract

This study investigates the role of Interleukin 17 (IL-17) in exacerbating periapical lesions caused by Porphyromonas gingivalis (Pg) lipopolysaccharides (LPS) in the context of metabolic disease and its potential impact on glucose tolerance. Researchers developed a unique mouse model where mice were monocolonized with Pg to induce periapical lesions. After 1 month, they were fed a high-fat diet (HFD) for 2 months to simulate metabolic disease and oral microbiota dysbiosis. To explore the role of LPS from Pg, wild-type (WT) mice were challenged with purified LPS from Porphyromonas gingivalis, as well as with LPS-depleted and non-depleted Pg bacteria; IL-17 knockout (KO) mice were also included to assess the role of IL-17 signaling. The impact on bone lysis, periapical injury, glucose intolerance, and immune response was assessed. Results showed that in WT mice, the presence of LPS significantly worsened bone lysis, Th17 cell recruitment, and periapical injury. IL-17 KO mice exhibited reduced bone loss, glucose intolerance, and immune cell infiltration. Additionally, inflammatory markers in adipose tissue were lower in IL-17 KO mice, despite increased dysbiosis. The findings suggest that IL-17 plays a critical role in amplifying Pg-induced periapical lesions and systemic metabolic disturbances. Targeting IL-17 recruitment could offer a novel approach to improving glycemic control and reducing type 2 diabetes (T2D) risk in individuals with periapical disease.

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