Links Between Insulin Resistance and Periodontal Bacteria: Insights on Molecular Players and Therapeutic Potential of Polyphenols

Type 2 diabetes is a metabolic disease mainly associated with insulin resistance during obesity and constitutes a major public health problem worldwide. A strong link has been established between type 2 diabetes and periodontitis, an infectious dental disease characterized by chronic inflammation and destruction of the tooth-supporting tissue or periodontium. However, the molecular mechanisms linking periodontal bacteria and insulin resistance remain poorly elucidated. This study aims to summarize the mechanisms possibly involved based on in vivo and in vitro studies and targets them for innovative therapies. Indeed, during periodontitis, inflammatory lesions of the periodontal tissue may allow periodontal bacteria to disseminate into the bloodstream and reach tissues, including adipose tissue and skeletal muscles that store glucose in response to insulin. Locally, periodontal bacteria and their components, such as lipopolysaccharides and gingipains, may deregulate inflammatory pathways, altering the production of pro-inflammatory cytokines/chemokines. Moreover, periodontal bacteria may promote ROS overproduction via downregulation of the enzymatic antioxidant defense system, leading to oxidative stress. Crosstalk between players of inflammation and oxidative stress contributes to disruption of the insulin signaling pathway and promotes insulin resistance. In parallel, periodontal bacteria alter glucose and lipid metabolism in the liver and deregulate insulin production by pancreatic β-cells, contributing to hyperglycemia. Interestingly, therapeutic management of periodontitis reduces systemic inflammation markers and ameliorates insulin sensitivity in type 2 diabetic patients. Of note, plant polyphenols exert anti-inflammatory and antioxidant activities as well as insulin-sensitizing and anti-bacterial actions. Thus, polyphenol-based therapies are of high interest for helping to counteract the deleterious effects of periodontal bacteria and improve insulin resistance.