High-Fat Diet Induces Periodontitis in Mice through Lipopolysaccharides (LPS) Receptor Signaling: Protective Action of Estrogens

Abstract

BackgroundA fat-enriched diet favors the development of gram negative bacteria in the intestine which is linked to the occurrence of type 2 diabetes (T2D). Interestingly, some pathogenic gram negative bacteria are commonly associated with the development of periodontitis which, like T2D, is characterized by a chronic low-grade inflammation. Moreover, estrogens have been shown to regulate glucose homeostasis via an LPS receptor dependent immune-modulation. In this study, we evaluated whether diet-induced metabolic disease would favor the development of periodontitis in mice. In addition, the regulatory role of estrogens in this process was assessed.MethodsFour-week-old C57BL6/J WT and CD14 (part of the TLR-4 machinery for LPS-recognition) knock-out female mice were ovariectomised and subcutaneously implanted with pellets releasing either placebo or 17β-estradiol (E2). Mice were then fed with either a normal chow or a high-fat diet for four weeks. The development of diabetes was monitored by an intraperitoneal glucose-tolerance test and plasma insulin concentration while periodontitis was assessed by identification of pathogens, quantification of periodontal soft tissue inflammation and alveolar bone loss.ResultsThe fat-enriched diet increased the prevalence of periodontal pathogenic microbiota like Fusobacterium nucleatum and Prevotella intermedia, gingival inflammation and alveolar bone loss. E2 treatment prevented this effect and CD14 knock-out mice resisted high-fat diet-induced periodontal defects.Conclusions/SignificanceOur data show that mice fed with a diabetogenic diet developed defects and microflora of tooth supporting-tissues typically associated with periodontitis. Moreover, our results suggest a causal link between the activation of the LPS pathway on innate immunity by periodontal microbiota and HFD-induced periodontitis, a pathophysiological mechanism that could be targeted by estrogens.

Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota

“…Furthermore, periodontal diseases themselves could be modulated by alteration of gut microbiota-induced systemic inflammation. In support of this hypothesis, it has been reported that high-fat diet-induced obesity increased alveolar bone resorption, a characteristic feature of periodontitis4445.…”

Estrogen protection against EAE modulates the microbiota and mucosal-associated regulatory cells

“…It was also suggested that estrogen-like compounds may be metabolized by gut microbes to produce estrogenic metabolites that could affect the immune system (Chen and Madak-Erdogan, 2016). High fat diets were shown to increase the lipopolysaccharide (LPS) producing Gram-negative bacteria, whereas estrogen was reported to reduce LPS-induced inflammation and decrease the concentration of these bacteria (Blasco-Baque et al, 2012). While further experiments are needed to determine whether the microbiota composition, which was observed in estrogen-treated mice is sufficient to induce protection against EAE, these findings point to a feedback loop between sex hormones and gut microbiota that affects the immune system.…”

Periodontal disease and percentage of calories from fat using national data

“…A review of the potential mechanisms of periodontal inflammation and nutritional factors provided advice on how to be healthy by encouraging the consumption of fruit and vegetables (which contain antioxidants) fish oil (which contains omega‐3 polyunsaturated fats), and emphasized the risk of diets that are high in refined carbohydrates . The results of an experiment performed in animals showed that a high‐fiber, low‐fat diet improves periodontal disease markers , and another study showed that a high‐fat diet was associated with worsening periodontal disease . Furthermore, serum albumin, which is considered to be an index of nutritional status, has been found to be negatively correlated with periodontal disease .…”