Project description:Background. Hematopoietic cell transplantation (HCT) is a potentially curative therapy for a wide range of pediatric malignant and nonmalignant diseases. However, complications, including blood stream infection (BSI) remain a major cause of morbidity and mortality. While certain bacteria that are abundant in the oral microbiome, such as S. mitis, can cause BSI, the role of the oral microbial community in the etiology of BSI is not well understood. The finding that the use of xylitol wipes, which specifically targets the cariogenic bacteria S. mutans is associated with reduced BSI in pediatric patients, lead us to investigate dental caries as a risk factor for BSI. Methods. A total of 41 pediatric patients admitted for allogenic or autologous HCT, age 8 months to 25 years, were enrolled. Subjects with high dental caries risk were identified as those who had dental restorations completed within 2 months of admission for transplant, or who had untreated decay. Fisher’s exact test was used to determine if there was a significant association between caries risk and BSI. Dental plaque and saliva were collected on a cotton swab from a subset of 4 high caries risk (HCR) and 4 low caries risk (LCR) children following pretransplant conditioning. 16SrRNA sequencing was used to compare the microbiome of HCR and LCR subjects and to identify microbes that were significantly different between the 2 groups. Results. There was a statistically significant association between caries risk and BSI (p<0.035) (Fisher’s exact test). Multivariate logistic regression analysis showed children in the high dental caries risk group were 21.39 times more likely to have BSI, with no significant effect of age or mucositis severity. HCR subjects showed significantly reduced microbial alpha diversity as compared to LCR subjects. LEfse metagenomic analyses, showed the oral microbiome in HCR children enriched in order Lactobacillales. This order includes Streptococcus and Lactobacillus, both which contain bacteria primarily associated with dental caries. Discussion. These findings support the possibility that the cariogenic microbiome can enhance the risk of BSI in pediatric populations. Future metagenomic analyses to measure microbial differences at, before, and after conditioning related to caries risk, may further unravel the complex relationship between the oral microbiome, and whether it affects health outcomes such as BSI.
Project description:The study aims to assess gene expression in plaque samples collected from twin pairs that are both concordant and discordant with respect to dental Caries diagnosis. File Naming Conventions are as follows: Patient ID : 4 digit identifier Diagnosis : Caries Negative(CN) or Caries Positive(CP) Type of Twin: Monozygotic(MZ)or Dizygotic(DZ) Pair to xxxx: 4 digit twin identifier maps to the Patient ID E.g: 2126_CP_MZ_PairTo_2125_fastqc - 2126 is a caries positive patient and pairs to monozygotic twin pair 2125. Plaque samples from twin pairs that are both concordant and discordant with respect to dental Caries diagnosis are enriched for bacterial messenger RNA to study the gene expression differences in the samples. RNA was extracted from RNAprotect (Qiagen, In c.) treated dental plaque scrapings from 38 patients. Amplified cDNA was created and rRNA sequence was removed by subtractive hybridization. Individual patient samples were run on a single lane of an Illumina Genome Analyzer.
Project description:The study aims to assess gene expression in plaque samples collected from twin pairs that are both concordant and discordant with respect to dental Caries diagnosis. File Naming Conventions are as follows: Patient ID : 4 digit identifier Diagnosis : Caries Negative(CN) or Caries Positive(CP) Type of Twin: Monozygotic(MZ)or Dizygotic(DZ) Pair to xxxx: 4 digit twin identifier maps to the Patient ID E.g: 2126_CP_MZ_PairTo_2125_fastqc - 2126 is a caries positive patient and pairs to monozygotic twin pair 2125. Plaque samples from twin pairs that are both concordant and discordant with respect to dental Caries diagnosis are enriched for bacterial messenger RNA to study the gene expression differences in the samples.
Project description:Streptococcus mutans is a common constituent of oral biofilms and a primary etiologic agent of human dental caries. The bacteria associated with dental caries have a potent ability to produce organic acids from dietary carbohydrates and to grow and metabolize in acidic conditions. In this study, we observed supplementation with 1.5% arginine (final concentration) had inhibitory effects on the growth of S. mutans in complex and chemically defined media, particularly when cells were exposed to acid or oxidative stress. Deep-sequencing of RNA (RNA-Seq) comparing the transcriptomes of S. mutans growing in a chemically defined medium with and without 1.5% arginine in neutral and acidic pH conditions and under oxidative stress conditions revealed interesting results. The results provide new insights into the mechanisms of action by which arginine inhibits dental caries through direct adverse effects on multiple virulence-related properties of the most common human dental caries pathogen. The findings significantly enhance our understanding of the genetics and physiology of this cariogenic pathogen.
Project description:We present a collection of single-cell transcriptomic profiles of 6,810 pulpal cells isolated from a sound human maxillary third molars and carious teeth at different stages. We showed that the presence of deep, but not enamel caries, altered the immune cell compositions of the dental pulp. Differential expression analysis further revealed that the pro-inflammatory, anti-inflammatory and mineralization-related genes were upregulated in immune and stromal cells in deep dental caries. Cell-cell interaction prediction showed potential interactions between immune and stromal cells during homeostasis, and enhanced interactions between different cell types with macrophage during deep dental caries. Taken together, our study serves as a comprehensive survey of human pulpal cell heterogeneity, as well as provides novel molecular insights into dental pulps in health and disease.
Project description:Human saliva microbiota is phylogenetically divergent among host individuals yet their roles in health and disease are poorly appreciated. We employed a microbial functional gene microarray, HuMiChip 1.0, to reconstruct the global functional profiles of human saliva microbiota from ten healthy and ten caries-active adults. Saliva microbiota in the pilot population featured a vast diversity of functional genes. No significant distinction in gene number or diversity indices was observed between healthy and caries-active microbiota. However, co-presence network analysis of functional genes revealed that caries-active microbiota was more divergent in non-core genes than healthy microbiota, despite both groups exhibited a similar degree of conservation at their respective core genes. Furthermore, functional gene structure of saliva microbiota could potentially distinguish caries-active patients from healthy hosts. Microbial functions such as Diaminopimelate epimerase, Prephenate dehydrogenase, Pyruvate-formate lyase and N-acetylmuramoyl-L-alanine amidase were significantly linked to caries. Therefore, saliva microbiota carried disease-associated functional signatures, which could be potentially exploited for caries diagnosis. The DMFT INDEX (Decayed, Missing, Filled [DMF] teeth index used in dental epidemiology) values are provided for each sample
Project description:In a prior report, we observed two distinct lung microbiomes in healthy subjects that we termed â??pneumotypesâ??: pneumotypeSPT, characterized by high bacterial load and supraglottic predominant taxa (SPT) such as the anaerobes Prevotella and Veillonella; and pneumotypeBPT, with low bacterial burden and background predominant taxa (BPT) found in the saline lavage and bronchoscope. Here, we determined the prevalence of these two contrasting lung microbiome types, in a multi-center study of healthy subjects. We confirmed that a lower airway microbiome enriched with upper airway microbes (pneumotypeSPT) was present in ~45% of healthy individuals. Cross-sectional Multicenter cohort. BAL of 49 healthy subjects from three cohort had their lower airway microbiome assessed by 16S rDNA sequencing and microbial gene content (metagenome) was computationally inferred from taxonomic assignments. The amplicons from total 100 samples are barcoded; the barcode and other clinical characteristics (e.g. inflammatory biomarkers and metabolome data) for each sample are provided in the 'Pneumotype.sep.Map.A1.txt' file.