Project description:Transcriptional profiling was utilized to define the biological pathways of gingival epithelial cells modulated by co-culture with the oral commensal S. gordonii and the opportunistic commensal F. nucleatum. We used microarrays to detail the global programme of gene expression underlying infection and identified distinct classes of up- and down-regulated genes during this process. Experiment Overall Design: Gingival epithelial HIGK cells were sham infected (CTRL) and infected with either the oral commensal S. gordonii (Sg) or the opportunistic commensal F. nucleatum (Fn). These samples were hybridized to Affymetrix microarrays. Understanding how host cells have adapted to commensals, and how barrier cells respond to limit their impact, provides a mechanistic biological basis of health in the mixed bacterial-human ecosystem of the oral cavity.
Project description:Transcriptional profiling was utilized to define the biological pathways of gingival epithelial cells modulated by mono- and complex co-culture with oral commensal S. gordonii and pathogenic P. gingivalis. We used microarrays to detail the global programme of gene expression underlying infection and identified distinct classes of up- and down-regulated genes during this process. Experiment Overall Design: Gingival epithelial HIGK cells were sham infected (CTRL) and infected with either the oral commensal S. gordonii (Sg) or the pathogenic P. gingivalis (Pg) as well as co-cultured in mixed cultures of Sg and Pg (Sg+Pg). These samples were hybridized to Affymetrix microarrays. Understanding how host cells have adapted to commensals, and how barrier cells respond to limit their impact, provides a mechanistic biological basis of health in the mixed bacterial-human ecosystem of the oral cavity and provides insight on how the degree of complexity of a microbiome influences this balance.
Project description:<p>Bacterial metabolism in oral biofilms is comprised of complex networks of nutritional chains and biochemical regulations. These processes involve both intraspecies and interspecies networks as well as interactions with components from host saliva, gingival crevicular fluid, and dietary intake. In a previous paper, a large salivary glycoprotein, mucin MUC5B, was suggested to promote a dental health-related phenotype in the oral type strain of <em>Streptococcus gordonii</em> DL1, by regulating bacterial adhesion and protein expression. In this study, nuclear magnetic resonance-based metabolomics was used to examine the effects on the metabolic output of monospecies compared to dual species early biofilms of two clinical strains of oral commensal bacteria, <em>S. gordonii</em> and <em>Actinomyces naeslundii</em>, in the presence of MUC5B. The presence of <em>S. gordonii</em> increased colonization of <em>A. naeslundii</em> on salivary MUC5B, and both commensals were able to utilize MUC5B as a sole nutrient source during early biofilm formation. The metabolomes suggested that the bacteria were able to release mucin carbohydrates from oligosaccharide side chains as well as amino acids from the protein core. Synergistic effects were also seen in the dual species biofilm metabolome compared to the monospecies, indicating that <em>A. naeslundii</em> and <em>S. gordonii</em> cooperated in the degradation of salivary MUC5B. A better understanding of bacterial interactions and salivary-mediated regulation of early dental biofilm activity is meaningful for understanding oral biofilm physiology and may contribute to the development of future prevention strategies for biofilm-induced oral disease.</p>
Project description:Opportunistic oral infections are ultimately presented in a vast majority of HIV-infected patients, often causing debilitating lesions that also contribute to deterioration in nutritional health. Although appreciation for the role that the microbiota is likely to play in the initiation and/or enhancement of oral infections has grown considerably in recent years, little is known about the impact of HIV infection on host-microbe interactions within the oral cavity. In the current study, we characterize modulations in the bacterial composition of the lingual microbiome in patients with treated and untreated HIV infection. Bacterial species profiles were elucidated by microarray assay and compared between untreated HIV infected patients, HIV infected patients receiving antiretroviral therapy, and healthy HIV negative controls. The relationship between clinical parameters (viral burden and CD4+ T cell depletion) and the loss or gain of bacterial species was evaluated in each HIV patient group. Characterization of modulations in the dorsal tongue (lingual) microbiota that are associated with chronic HIV infection.
Project description:To understand what molecular mechanisms determine the unique interspecies interactions between two predominant oral commensals Streptococcus sanguinis and Corynebacterium durum in the healthy oral cavity. We further investigated the regulatory connection between lipid metabolism and chain elongation based on the global gene expression profiling of the dual species cultures, as well as characterized S. sanguinis glycerol kinase (glpK) as a key gene involved in the interspecies interactions.
Project description:Although oral antibiotics can predispose to joint inflammation, this phenomenon remains poorly understood. Here, we leverage mouse models of alphavirus arthritis to investigate the gut commensals, metabolites, and host mechanisms that promote musculoskeletal inflammation. Mice treated with a short course of oral antibiotics exhibited worsened arthritis after chikungunya virus (CHIKV) infection. This phenotype was associated with loss of short chain fatty acids (SCFA) and greater intestinal permeability, and required TLR4 signaling, MyD88 expression, monocytes, antigen-specific and bystander CD4+ T cells, and pro-inflammatory cytokines. Administration of exogenous SCFA or colonization of mice with bacterial species that generate SCFA mitigated CHIKV-induced joint inflammation. Single cell RNA sequencing revealed that gut-derived SCFA restrain the inflammatory phenotype of synovial CD4+ T cells and limit activation of monocytes and osteoclast-like cells. Thus, antibiotic-triggered gut dysbiosis exacerbates alphavirus arthritis by shaping the inflammatory profile of both infiltrating and resident immune cells in joint tissues.
Project description:The initial exposure to pathogens and commensals confers innate immune cells the capacity to respond distinctively upon a second stimulus. This training capacity might play key functions in developing an adequate innate immune response to the continuous exposure to bacteria. However, the mechanisms involved in induction of trained immunity by commensals remain mostly unexplored. A. muciniphila represents an attractive candidate to study the promotion of these long-term responses. Here, we show that priming of macrophages with live A. muciniphila enhances bacterial intracellular survival and decreases the release of pro- and anti-inflammatory signals, lowering the production of TNF and IL-10. Global transcriptional analysis of macrophages after a secondary exposure to the bacteria showed the transcriptional rearrangement underpinning the phenotype observed compared to acutely exposed cells, with the increased expression of genes related to phagocytic capacity and those involved in the metabolic adjustment conducing to innate immune training. Accordingly, key genes related to bacterial killing and pro-inflammatory pathways were downregulated. These data demonstrate the importance of specific bacterial members in the modulation of local long-term innate immune responses, broadening our knowledge of the association between gut microbiome commensals and trained immunity as well as the anti-inflammatory probiotic potential of A. muciniphila.
Project description:Transcriptional profiling was utilized to define the biological pathways of gingival epithelial cells modulated by co-culture with the oral pathogenic Porphyromonas gingivalis and Aggregatibacter (formerly actinobacillus) actinomycetemcomitans. We used microarrays to detail the global programme of gene expression underlying infection and identified distinct classes of up- and down-regulated genes during this process. Experiment Overall Design: Gingival epithelial HIGK cells were sham infected (CTRL) and infected with either the oral pathogenic P. gingivalis (Pg) or A. actinomycetemcomitans (Aa). These samples were hybridized to Affymetrix microarrays. Understanding how host cells have adapted to pathogens, and how barrier cells respond to limit their impact, provides a mechanistic biological basis of microbial disease in the mixed bacterial-human ecosystem of the oral cavity.
Project description:Periodontitis patients often develop bacteremia, but there has been little evidence showing that oral bacteria translocate into other organs. We found that bacterial colony formation occurs in a culture of liver and spleen cells of periodontitis-induced mice, and the bacterial species detected in the liver and spleen were found in the oral cavity as well, but not in fecal samples, indicating systemic dissemination of oral bacteria during the breakdown of the oral barrier.
2018-01-26 | GSE109664 | GEO
Project description:The pulmonary commensals enhance resistance against bacterial infections