Summary Streptococcus mutans regulates genetic competence through a complex network that receives inputs from a number of environmental stimuli, including two signaling peptides designated as CSP and XIP. The response of the downstream competence genes to these inputs shows evidence of stochasticity and bistability and has been difficult to interpret. We have used microfluidic, single-cell methods to study how combinations of extracellular signals shape the response of comX, an alternative sigma factor governing expression of the late competence genes. We find that the composition of the medium determines which extracellular signal (XIP or CSP) can elicit a response from comX and whether that response is unimodal or bimodal across a population of cells. In a chemically defined medium, exogenous CSP does not induce comX, whereas exogenous XIP elicits a comX response from all cells. In complex medium, exogenous XIP does not induce comX, whereas CSP elicits a bimodal comX response from the population. Interestingly, bimodal behavior required an intact copy of comS, which encodes the precursor of XIP. The comS-dependent capability for both unimodal and bimodal response suggests that a constituent – most likely peptides – of complex medium interacts with a positive feedback loop in the competence regulatory network.

Microbes colonize human oral surfaces within hours after delivery. During postnatal development, physiological changes, such as the eruption of primary teeth and replacement of the primary dentition with permanent dentition, greatly alter the microbial habitats, which, in return, may lead to community composition shifts at different phases in people's lives. By profiling saliva, supragingival and mucosal plaque samples from healthy volunteers at different ages and dentition stages, we observed that the oral cavity is a highly heterogeneous ecological system containing distinct niches with significantly different microbial communities. More importantly, the phylogenetic microbial structure varies with ageing. In addition, only a few taxa were present across the whole populations, indicating a core oral microbiome should be defined based on age and oral niches.

Postmenopausal osteoporosis (PMO) is a risk factor for periodontitis, and current therapeutics against PMO prevent the aggravated alveolar bone loss of periodontitis in estrogen-deficient women. Gut microbiota is recognized as a promising therapeutic target for PMO. Berberine extracted from Chinese medicinal plants has shown its effectiveness in the treatment of metabolic diseases such as obesity and diabetes via regulating gut microbiota. Here, we hypothesize that berberine ameliorates periodontal bone loss by improving the intestinal barriers by regulating gut microbiota under an estrogen-deficient condition. Experimental periodontitis was established in ovariectomized (OVX) rats, and the OVX-periodontitis rats were treated with berberine for 7 wk before sacrifice for analyses. Micro-computed tomography and histologic analyses showed that berberine treatment significantly reduced alveolar bone loss and improved bone metabolism of OVX-periodontitis rats as compared with the vehicle-treated OVX-periodontitis rats. In parallel, berberine-treated OVX-periodontitis rats harbored a higher abundance of butyrate-producing gut microbiota with elevated butyrate generation, as demonstrated by 16S rRNA sequencing and high-performance liquid chromatography analysis. Berberine-treated OVX-periodontitis rats consistently showed improved intestinal barrier integrity and decreased intestinal paracellular permeability with a lower level of serum endotoxin. In parallel, IL-17A-related immune responses were attenuated in berberine-treated OVX-periodontitis rats with a lower serum level of proinflammatory cytokines and reduced IL-17A cells in alveolar bone as compared with vehicle-treated OVX-periodontitis rats. Our data indicate that gut microbiota is a potential target for the treatment of estrogen deficiency-aggravated periodontal bone loss, and berberine represents a promising adjuvant therapeutic by modulating gut microbiota.

BackgroundIt is widely accepted that oral health plays an important role in overall health. Both dental and medical students are expected to possess good oral health awareness and work together for public oral health promotion especially in developing countries like China. The aim of this study was to assess the oral health knowledge, behavior and status of dental and medical undergraduate students in the first (fresh) and third year (before specialized courses) study.MethodsA self-administered structured questionnaire with 13 questions was designed based on oral health knowledge, behavior and status and a cross-sectional study was conducted among the 1st, 3rd year dental students (1DS, 3DS) and medical students (1MS, 3MS) of Sichuan University in Chengdu, China, in the period of September–December 2017. The data was analyzed by chi-square test using IBM SPSS Statistics v. 21.0.ResultsThe oral health behavior, consciousness and status of the 1st, 3rd year medical and dental students were not optimistic. Dental freshmen were slightly superior to the medical ones in terms of the brushing methods and the awareness of oral disease-systemic disease relationship. The junior dental students showed highly significant improvement than their counterparts, mainly in the items about frequency of brushing teeth, brushing methods of vertical scrub or Bass technique (66.3%), usage of floss or mouth wash (49.7%), causes of caries, periodontal diseases and system diseases (56.9–83.4%). The rates mentioned above were 36.1, 15.8%, 26.7–43.6% among 3MS, respectively. In terms of oral health status, significant differences were only observed in junior students. The prevalence rates of bad breath, gum bleeding, and tooth discoloration among 3DS were obviously lower than those of 3MS. However, only a total of 17.2% junior students had a good oral health, including 23.8% dental students and 11.4% medical students.ConclusionsOur study provided a new understanding of oral health knowledge, behavior and status among dental and medical students, which may help to promote the reform of oral health education and establish a model for clinicians and dentists to work together for improving oral health.

The development of competence by the dental caries pathogen Streptococcus mutans is mediated primarily through the alternative sigma factor ComX (SigX), which is under the control of multiple regulatory systems and activates the expression of genes involved in DNA uptake and recombination. Here we report that the induction of competence and competence gene expression by XIP (sigX-inducing peptide) and CSP (competence-stimulating peptide) is dependent on the growth phase and that environmental pH has a potent effect on the responses to XIP. A dramatic decline in comX and comS expression was observed in midand late-exponential-phase cells. XIP-mediated competence development and responses to XIP were optimal around a neutral pH, although mid-exponential-phase cells remained refractory to XIP treatment, and acidified late-exponential-phase cultures were resistant to killing by high concentrations of XIP. Changes in the expression of the genes for the oligopeptide permease (opp), which appears to be responsible for the internalization of XIP, could not entirely account for the behaviors observed. Interestingly, comS and comX expression was highly induced in response to endogenously overproduced XIP or ComS in mid-exponential-phase cells. In contrast to the effects of pH on XIP, competence induction and responses to CSP in complex medium were not affected by pH, although a decreased response to CSP in cells that had exited early-exponential phase was observed. Collectively, these results indicate that competence development may be highly sensitive to microenvironments within oral biofilms and that XIP and CSP signaling in biofilms could be spatially and temporally heterogeneous.