The genus Roseburia consists of obligate Gram-positive anaerobic bacteria that are slightly curved, rod-shaped and motile by means of multiple subterminal flagella. It includes five species: Roseburia intestinalis, R. hominis, R. inulinivorans, R. faecis and R. cecicola. Gut Roseburia spp. metabolize dietary components that stimulate their proliferation and metabolic activities. They are part of commensal bacteria producing short-chain fatty acids, especially butyrate, affecting colonic motility, immunity maintenance and anti-inflammatory properties. Modification in Roseburia spp. representation may affect various metabolic pathways and is associated with several diseases (including irritable bowel syndrome, obesity, Type 2 diabetes, nervous system conditions and allergies). Roseburia spp. could also serve as biomarkers for symptomatic pathologies (e.g., gallstone formation) or as probiotics for restoration of beneficial flora.

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ObjectiveTo identify a causal mechanism responsible for the enhancement of insulin resistance and hyperglycaemia following periodontitis in mice fed a fat-enriched diet.DesignWe set-up a unique animal model of periodontitis in C57Bl/6 female mice by infecting the periodontal tissue with specific and alive pathogens like Porphyromonas gingivalis (Pg), Fusobacterium nucleatum and Prevotella intermedia. The mice were then fed with a diabetogenic/non-obesogenic fat-enriched diet for up to 3 months. Alveolar bone loss, periodontal microbiota dysbiosis and features of glucose metabolism were quantified. Eventually, adoptive transfer of cervical (regional) and systemic immune cells was performed to demonstrate the causal role of the cervical immune system.ResultsPeriodontitis induced a periodontal microbiota dysbiosis without mainly affecting gut microbiota. The disease concomitantly impacted on the regional and systemic immune response impairing glucose metabolism. The transfer of cervical lymph-node cells from infected mice to naive recipients guarded against periodontitis-aggravated metabolic disease. A treatment with inactivated Pg prior to the periodontal infection induced specific antibodies against Pg and protected the mouse from periodontitis-induced dysmetabolism. Finally, a 1-month subcutaneous chronic infusion of low rates of lipopolysaccharides from Pg mimicked the impact of periodontitis on immune and metabolic parameters.ConclusionsWe identified that insulin resistance in the high-fat fed mouse is enhanced by pathogen-induced periodontitis. This is caused by an adaptive immune response specifically directed against pathogens and associated with a periodontal dysbiosis.

BackgroundAbdominal Aortic Aneurysms (AAAs) represent a particular form of atherothrombosis where neutrophil proteolytic activity plays a major role. We postulated that neutrophil recruitment and activation participating in AAA growth may originate in part from repeated episodes of periodontal bacteremia.Methods and FindingsOur results show that neutrophil activation in human AAA was associated with Neutrophil Extracellular Trap (NET) formation in the IntraLuminal Thrombus, leading to the release of cell-free DNA. Human AAA samples were shown to contain bacterial DNA with high frequency (11/16), and in particular that of Porphyromonas gingivalis (Pg), the most prevalent pathogen involved in chronic periodontitis, a common form of periodontal disease. Both DNA reflecting the presence of NETs and antibodies to Pg were found to be increased in plasma of patients with AAA. Using a rat model of AAA, we demonstrated that repeated injection of Pg fostered aneurysm development, associated with pathological characteristics similar to those observed in humans, such as the persistence of a neutrophil-rich luminal thrombus, not observed in saline-injected rats in which a healing process was observed.ConclusionsThus, the control of periodontal disease may represent a therapeutic target to limit human AAA progression.

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Periodontitis is driven by disproportionate host inflammatory immune responses induced by an imbalance in the composition of oral bacteria; this instigates microbial dysbiosis, along with failed resolution of the chronic destructive inflammation. The objectives of this study were to identify microbial signatures for health and chronic periodontitis at the genus level and to propose a model of dysbiosis, including the calculation of bacterial ratios. Published sequencing data obtained from several different studies (196 subgingival samples from patients with chronic periodontitis and 422 subgingival samples from healthy subjects) were pooled and subjected to a new microbiota analysis using the same Visualization and Analysis of Microbial Population Structures (VAMPS) pipeline, to identify microbiota specific to health and disease. Microbiota were visualized using CoNet and Cytoscape. Dysbiosis ratios, defined as the percentage of genera associated with disease relative to the percentage of genera associated with health, were calculated to distinguish disease from health. Correlations between the proposed dysbiosis ratio and the periodontal pocket depth were tested with a different set of data obtained from a recent study, to confirm the relevance of the ratio as a potential indicator of dysbiosis. Beta diversity showed significant clustering of periodontitis-associated microbiota, at the genus level, according to the clinical status and independent of the methods used. Specific genera (Veillonella, Neisseria, Rothia, Corynebacterium, and Actinomyces) were highly prevalent (Ͼ95%) in health, while other genera (Eubacterium, Campylobacter, Treponema, and Tannerella) were associated with chronic periodontitis. The calculation of dysbiosis ratios based on the relative abundance of the genera found in health versus periodontitis was tested. Nonperiodontitis samples were significantly identifiable by low ratios, compared to chronic periodontitis samples. When applied to a subgingival sample set with well-defined clinical data, the method showed a strong correlation between the dysbiosis ratio, as well as a simplified ratio (Porphyromonas, Treponema, and Tannerella to Rothia and Corynebacterium), and pocket depth. Microbial analysis of chronic periodontitis can be correlated with the pocket depth through specific signatures for microbial dysbiosis.IMPORTANCE Defining microbiota typical of oral health or chronic periodontitis is difficult. The evaluation of periodontal disease is currently based on probing of the periodontal pocket. However, the status of pockets "on the mend" or sulci at risk of periodontitis cannot be addressed solely through pocket depth measurements or current microbiological tests available for practitioners. Thus, a more specific microbiological measure of dysbiosis could help in future diagnoses of periodontitis. In this work, data from different studies were pooled, to improve the accuracy of the results. However, analysis of multiple species from different studies intensified the bacteri...

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Heritable hypermutation in bacteria is mainly due to alterations in the methyl-directed mismatch repair (MMR) system. MMR-deficient strains have been described from several bacterial species, and all of the strains exhibit increased mutation frequency and recombination, which are important mechanisms for acquired drug resistance in bacteria. Antibiotics select for drug-resistant strains and refine resistance determinants on plasmids, thus stimulating DNA recombination via the MMR system. Antibiotics can also act as indirect promoters of antibiotic resistance by inducing the SOS system and certain error-prone DNA polymerases. These alterations have clinical consequences in that efficacious treatment of bacterial infections requires high doses of antibiotics and/or a combination of different classes of antimicrobial agents. There are currently few new drugs with low endogenous resistance potential, and the development of such drugs merits further research. IntroductionEradication of infectious diseases is constantly challenged by micro-organisms that develop new survival strategies. Previous studies suggest that mutational events play a predominant role in bacterial adaptation and confer a selective advantage (Chou et al., 2009;Cooper, 2007). Early experiments aimed at detecting mutators used mutagenized laboratory strains of bacteria, sometimes coupled with different selection strategies. LeClerc et al. (1996) reported high mutation frequency among Escherichia coli and Salmonella pathogens, challenging the theory that mutators were rare among bacterial populations. Taken together, these findings demonstrated that natural populations could respond to environmental selection in two ways, i.e. by enhanced mutation frequencies and by recombination. Transient mutator status, which involves reversion or recombination within the mutator alleles or depletion of the methyl-directed mismatch repair (MMR) system proteins, allows the organism to temporarily benefit from the elevated mutation frequency for adaptation while reducing the risk of accumulating deleterious mutations. Using a mathematical model, Rosche & Foster (1999) showed that transient hypermutators play a role in adaptive mutation in E. coli. Molecular mechanisms of hypermutationProteins involved in the DNA mismatch repair pathway help replace nucleotides introduced erroneously into the replicated DNA and also hinder recombination between non-identical DNA sequences. Deficiencies in any of the DNA mismatch repair pathway mechanisms can lead to a hypermutator phenotype. DNA repairSiegel & Bryson (1967) discovered the mutS gene in an azaserine-resistant derivative of E. coli that had a mutator phenotype and carried a deletion in the mutS gene. The majority of naturally occurring strong mutators have defects in the MMR system; the mutations are mainly in mutS (Oliver et al., 2002), but deletions in genes encoding beta-clamp proteins and in mutH, mutL and mutU (uvrD) have also been described (Fig. 1). Inactivation of basal excision repair genes, e.g. mutY, mutM, ...