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Introduction: The impaired host defense system in HIV infection impacts the oral and gastrointestinal microbiota and associated opportunistic infections. Antiretroviral treatment is predicted to partially restore host defenses and decrease the oral manifestation of HIV/AIDS. Well-designed longitudinal studies are needed to better understand the interactions of soluble host defense proteins with bacteria and virus in HIV/AIDS. “Crosstalk” was designed as a longitudinal study of host responses along the gastrointestinal (GI) tract and interactions between defense molecules and bacteria in HIV infection and subsequent therapy. Purpose: The clinical core formed the infrastructure for the study of the interactions between the proteome, microbiome and innate immune system. The core recruited and retained study subjects, scheduled visits, obtained demographic and medical data, assessed oral health status, collected samples, and guided analysis of the hypotheses. This manuscript presents a well-designed clinical core that may serve as a model for studies that combine clinical and laboratory data. Methods: Crosstalk was a case-control longitudinal clinical study an initial planned enrollment of 170 subjects. HIV+ antiretroviral naïve subjects were followed for 9 visits over 96 weeks and HIV uninfected subjects for 3 visits over 24 weeks. Clinical prevalence of oral mucosal lesions, dental caries and periodontal disease were assessed. Results: During the study, 116 subjects (47 HIV+, 69 HIV-) were enrolled. Cohorts of HIV+ and HIV- were demographically similar except for a larger proportion of women in the HIV- group. The most prevalent oral mucosal lesions were oral candidiasis and hairy leukoplakia in the HIV+ group. Discussion: The clinical core was essential to enable the links between clinical and laboratory data. The study aims to determine specific differences between oral and GI tissues that account for unique patterns of opportunistic infections and to delineate the differences in their susceptibility to infection by HIV and their responses post-HAART. [ABSTRACT FROM AUTHOR]

Individual bacteria and shifts in the composition of the microbiome have been associated with human diseases including cancer. To investigate changes in the microbiome associated with oral cancers, we profiled cancers and anatomically matched contralateral normal tissue from the same patient by sequencing 16S rDNA hypervariable region amplicons. In cancer samples from both a discovery and a subsequent confirmation cohort, abundance of Firmicutes (especially Streptococcus) and Actinobacteria (especially Rothia) was significantly decreased relative to contralateral normal samples from the same patient. Significant decreases in abundance of these phyla were observed for pre-cancers, but not when comparing samples from contralateral sites (tongue and floor of mouth) from healthy individuals. Weighted UniFrac principal coordinates analysis based on 12 taxa separated most cancers from other samples with greatest separation of node positive cases. These studies begin to develop a framework for exploiting the oral microbiome for monitoring oral cancer development, progression and recurrence. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to assess the effects of dental flossing on the microbial composition of interproximal plaque samples in matched twins. Methods: The study was a two-treatment, examiner-masked, randomized, parallel-group, controlled study. Fifty-one twin pairs between 12 and 21 years of age were randomized to a 2-week supervised and unsupervised treatment regimen consisting of tongue brushing and toothbrushing or tongue brushing and toothbrushing plus flossing. The reversecapture checkerboard hybridization assay was used to assess levels (abundance) of 26 microbial species in interproximal plaque samples collected from six sites per subject. An integrative computational predictive model estimated average changes in microbial abundance patterns of selected bacterial species from baseline to 2 weeks by comparing treatment groups. Results: After the 2-week study period, putative periodontal pathogens and cariogenic bacteria were overabundant in the group that did not floss compared to the group that performed flossing. Those included Treponema denticola, Porphyromonas gingivalis, Tannerella torsythia (previously T. forsythensis), Prevotella intermedia, Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), and Streptococcus mutans. Microbial species that are not consistent with the development of periodontal disease or dental caries were overabundant in the group that did floss compared to the non-flossing group. Conclusion: In a well-matched twin cohort, tooth and tongue brushing plus flossing significantly decreased the abundance of microbial species associated with periodontal disease and dental caries after a 2-week program. [ABSTRACT FROM AUTHOR]

Oral microbes that colonize in the mouths of humans contribute to disease susceptibility, but it is unclear if host genetic factors mediate colonization. We therefore tested the hypothesis that the levels at which oral microbes colonize in the mouth are heritable. Dental plaque biofilms were sampled from intact tooth surfaces of 118 caries-free twins. An additional 86 caries-active twins were sampled for plaque from carious lesions and intact tooth surfaces. Using a reverse capture checkerboard assay the relative abundance of 82 bacterial species was determined. An integrative computational predictive model determined microbial abundance patterns of microbial species in caries-free twins as compared to caries-active twins. Heritability estimates were calculated for the relative microbial abundance levels of the microbial species in both groups. The levels of 10 species were significantly different in healthy individuals than in caries-active individuals, including, A. defectiva, S. parasanguinis, S. mitis/oralis, S. sanguinis, S. cristatus, S. salivarius, Streptococcus sp. clone CH016, G. morbillorum and G. haemolysans. Moderate to high heritability estimates were found for these species (h(2) = 56%-80%, p < .0001). Similarity of the overall oral microbial flora was also evident in caries-free twins from multivariate distance matrix regression analysis. It appears that genetic and/or familial factors significantly contribute to the colonization of oral beneficial species in twins. [ABSTRACT FROM AUTHOR]