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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.

The oral cavity is host to a complex and diverse microbiota community which plays an important role in health and disease. Major oral infections, i.e., caries and periodontal diseases, are both responsible for and induced by oral microbiota dysbiosis. This dysbiosis is known to have an impact on other chronic systemic diseases, whether triggering or aggravating them, making the oral microbiota a novel target in diagnosing, following, and treating systemic diseases. In this review, we summarize the major roles that oral microbiota can play in systemic disease development and aggravation and also how novel tools can help investigate this complex ecosystem. Finally, we describe new therapeutic approaches based on oral bacterial recolonization or host modulation therapies. Collaboration in diagnosis and treatment between oral specialists and general health specialists is of key importance in bridging oral and systemic health and disease and improving patients’ wellbeing.

The aim of this study was to analyze the link between oral microbiota and obesity in humans. We conducted a pilot study including 19 subjects with periodontitis divided into two groups: normo-weighted subjects (NWS) with a body mass index (BMI) between 20 and 25 (n = 9) and obese subjects (OS) with a BMI > 30 (n = 10). Obesity was associated with a poor oral health status characterized by an increased number of missing teeth and a higher score of periodontal-support loss associated with dysbiotic oral microbiota (39.45 ± 3.74 vs. 26.41 ± 11.21, p = 0.03 for the Chao 1 index). Oral microbiota taxonomic analysis showed that the abundance of the Capnocytophaga genus was higher (2.47% ± 3.02 vs. 0.27% ± 0.29, p = 0.04) in OS compared to NWS. Obese females (OF) were characterized by an increase in the Streptococcus genus (34.12% ± 14.29 vs. 10.55% ± 10.42, p = 0.05) compared to obese males (OM), where the Neisseria genus was increased (5.75% ± 5.03 vs. 58.05% ± 30.64, p = 0.008). These first data suggest that sex/gender is determinant in the link between oral dysbiotic microbiota and obesity in patients with periodontitis. Our results could lead to recommendations concerning therapeutic strategies for obese patients with periodontitis following the sex/gender.

Objective: To demonstrate that glycemia and insulin resistance are controlled by a mechanism involving the adaptive immune system and gut microbiota crosstalk. Methods: We triggered the immune system with microbial extracts specifically from the intestinal ileum contents of HFD-diabetic mice by the process of immunization. 35 days later, immunized mice were fed a HFD for up to two months in order to challenge the development of metabolic features. The immune responses were quantified. Eventually, adoptive transfer of immune cells from the microbiota-immunized mice to naïve mice was performed to demonstrate the causality of the microbiota-stimulated adaptive immune system on the development of metabolic disease. The gut microbiota of the immunized HFD-fed mice was characterized in order to demonstrate whether the manipulation of the microbiota to immune system interaction reverses the causal deleterious effect of gut microbiota dysbiosis on metabolic disease. Results: Subcutaneous injection (immunization procedure) of ileum microbial extracts prevented hyperglycemia and insulin resistance in a dose-dependent manner in response to a HFD. The immunization enhanced the proliferation of CD4 and CD8 T cells in lymphoid organs, also increased cytokine production and antibody secretion. As a mechanism explaining the metabolic improvement, the immunization procedure reversed gut microbiota dysbiosis. Finally, adoptive transfer of immune cells from immunized mice improved metabolic features in response to HFD. Conclusions: Glycemia and insulin sensitivity can be regulated by triggering the adaptive immunity to microbiota interaction. This reduces the gut microbiota dysbiosis induced by a fat-enriched diet. Keywords: Gut microbiota and metabolic diseases, Immunity, Insulin resistance

Abstract Background Gut microbiota is involved in the development of liver diseases such as fibrosis. We and others identified that selected sets of gut bacterial DNA and bacteria translocate to tissues, notably the liver, to establish a non-infectious tissue microbiota composed of microbial DNA and a low frequency live bacteria. However, the precise set of bacterial DNA, and thereby the corresponding taxa associated with the early stages of fibrosis need to be identified. Furthermore, to overcome the impact of different group size and patient origins we adapted innovative statistical approaches. Liver samples with low liver fibrosis scores (F0, F1, F2), to study the early stages of the disease, were collected from Romania(n = 36), Austria(n = 10), Italy(n = 19), and Spain(n = 17). The 16S rRNA gene was sequenced. We considered the frequency, sparsity, unbalanced sample size between cohorts to identify taxonomic profiles and statistical differences. Results Multivariate analyses, including adapted spectral clustering with L1-penalty fair-discriminant strategies, and predicted metagenomics were used to identify that 50% of liver taxa associated with the early stage fibrosis were Enterobacteriaceae, Pseudomonadaceae, Xanthobacteriaceae and Burkholderiaceae. The Flavobacteriaceae and Xanthobacteriaceae discriminated between F0 and F1. Predicted metagenomics analysis identified that the preQ0 biosynthesis and the potential pathways involving glucoryranose and glycogen degradation were negatively associated with liver fibrosis F1-F2 vs F0. Conclusions Without demonstrating causality, our results suggest first a role of bacterial translocation to the liver in the progression of fibrosis, notably at the earliest stages. Second, our statistical approach can identify microbial signatures and overcome issues regarding sample size differences, the impact of environment, and sets of analyses. Trial registration TirguMECCH ROLIVER Prospective Cohort for the Identification of Liver Microbiota, registration 4065/2014. Registered 01 01 2014.