Dysbiosis in salivary bacterial diversity of postpartum females and its association with oral health problems and APOs.
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ABSTRACT:
SUBMITTER: Khadija B
PROVIDER: S-EPMC8610344 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The gut microbiota has recently been recognized to play a role in the pathogenesis of autoimmune liver disease (AILD), mainly primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). This study aimed to analyze and compare the composition of the oral microbiota of 56 patients with AILD and 15 healthy controls (HCs) and to evaluate its association with salivary immunological biomarkers and gut microbiota. The subjects included 39 patients with PBC and 17 patients with AIH diagnosed at our hospital. The control population comprised 15 matched HCs. Salivary and fecal samples were collected for analysis of the microbiome by terminal restriction fragment length polymorphism of 16S rDNA. Correlations between immunological biomarkers measured by Bio-Plex assay (Bio-Rad) and the oral microbiomes of patients with PBC and AIH were assessed. Patients with AIH showed a significant increase in Veillonella with a concurrent decrease in Streptococcus in the oral microbiota compared with the HCs. Patients with PBC showed significant increases in Eubacterium and Veillonella and a significant decrease in Fusobacterium in the oral microbiota compared with the HCs. Immunological biomarker analysis showed elevated levels of inflammatory cytokines (IL-1β, IFN-γ, TNF-α, IL-8) and immunoglobulin A in the saliva of patients with AILD. The relative abundance of Veillonella was positively correlated with the levels of IL-1β, IL-8 and immunoglobulin A in saliva and the relative abundance of Lactobacillales in feces. Dysbiosis of the oral microbiota is associated with inflammatory responses and reflects changes in the gut microbiota of patients with AILD. Dysbiosis may play an important role in the pathogenesis of AILD.
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Project description:Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity and the fourth leading malignancy and cause of cancer-related death in the male population of Taiwan. Most cases are detected at advanced stages, resulting in poor prognosis. Therefore, improved detection of early oral health disorders is indispensable. The involvement of oral bacteria in inflammation and their association with OSCC progression provide a feasible target for diagnosis. Due to the nature of oral neoplasms, the diagnosis of epithelial precursor lesions is relatively easy compared with that of other types of cancer. However, the transition from an epithelial precursor lesion to cancer is slow and requires further and continuous follow-up. In this study, we investigated microbiota differences between normal individuals, epithelial precursor lesion patients, and cancer patients with different lifestyle habits, such as betel chewing and smoking, using next-generation sequencing. Overall, the oral microbiome compositions of five genera, Bacillus, Enterococcus, Parvimonas, Peptostreptococcus, and Slackia, revealed significant differences between epithelial precursor lesion and cancer patients and correlated with their classification into two clusters. These composition changes might have the potential to constitute a biomarker to help in monitoring the oral carcinogenesis transition from epithelial precursor lesion to cancer.
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Project description:Oral squamous cell carcinoma (OSCC) is the leading cause of mortality for oral cancer. Numerous risk factors mainly related to unhealthy habits and responsible for chronic inflammation and infections have been recognized as predisposing factors for oral carcinogenesis. Recently, even microbiota alterations have been associated with the development of human cancers. In particular, some specific bacterial strains have been recognized and strongly associated with oral cancer development (Capnocytophaga gingivalis, Fusobacterium spp., Streptococcus spp., Peptostreptococcus spp., Porphyromonas gingivalis and Prevotella spp.). Several hypotheses have been proposed to explain how the oral microbiota could be involved in cancer pathogenesis by mainly paying attention to chronic inflammation, microbial synthesis of cancerogenic substances, and alteration of epithelial barrier integrity. Based on knowledge of the carcinogenic effects of dysbiosis, it was recently suggested that probiotics may have anti-tumoral activity. Nevertheless, few data exist with regard to probiotic effects on oral cancer. On this basis, the association between the development of oral cancer and oral dysbiosis is discussed focusing attention on the potential benefits of probiotics administration in cancer prevention.
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Project description:Spatial and temporal patterns in microbial communities provide insights into the forces that shape them, their functions and roles in health and disease. Here, we used spatial and ecological statistics to analyze the role that saliva plays in structuring bacterial communities of the human mouth using >9000 dental and mucosal samples. We show that regardless of tissue type (teeth, alveolar mucosa, keratinized gingiva, or buccal mucosa), surface-associated bacterial communities vary along an ecological gradient from the front to the back of the mouth, and that on exposed tooth surfaces, the gradient is pronounced on lingual compared to buccal surfaces. Furthermore, our data suggest that this gradient is attenuated in individuals with low salivary flow due to Sjögren's syndrome. Taken together, our findings imply that salivary flow influences the spatial organization of microbial communities and that biogeographical patterns may be useful for understanding host physiological processes and for predicting disease.
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Project description:Studies in patients with genetic defects can provide unique insights regarding the role of specific genes and pathways in humans. Patients with defects in the Th17/IL-17 axis, such as patients harboring loss-of-function STAT3 mutations (autosomal-dominant hyper IgE syndrome; AD-HIES) present with recurrent oral fungal infections. Our studies aimed to comprehensively evaluate consequences of STAT3 deficiency on the oral commensal microbiome. We characterized fungal and bacterial communities in AD-HIES in the presence and absence of oral fungal infection compared with healthy volunteers. Analyses of oral mucosal fungal communities in AD-HIES revealed severe dysbiosis with dominance of Candida albicans (C. albicans) in actively infected patients and minimal representation of health-associated fungi and/or opportunists. Bacterial communities also displayed dysbiosis in AD-HIES, particularly in the setting of active Candida infection. Active candidiasis was associated with decreased microbial diversity and enrichment of the streptococci Streptococcus oralis (S. oralis) and S. mutans, suggesting an interkingdom interaction of C. albicans with oral streptococci. Increased abundance of S. mutans was consistent with susceptibility to dental caries in AD-HIES. Collectively, our findings illustrate a critical role for STAT3/Th17 in the containment of C. albicans as a commensal organism and an overall contribution in the establishment of fungal and bacterial oral commensal communities.
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Project description:BackgroundGastrointestinal mucosal injury (mucositis), commonly affecting the oral cavity, is a clinically significant yet incompletely understood complication of cancer chemotherapy. Although antineoplastic cytotoxicity constitutes the primary injury trigger, the interaction of oral microbial commensals with mucosal tissues could modify the response. It is not clear, however, whether chemotherapy and its associated treatments affect oral microbial communities disrupting the homeostatic balance between resident microorganisms and the adjacent mucosa and if such alterations are associated with mucositis. To gain knowledge on the pathophysiology of oral mucositis, 49 subjects receiving 5-fluorouracil (5-FU) or doxorubicin-based chemotherapy were evaluated longitudinally during one cycle, assessing clinical outcomes, bacterial and fungal oral microbiome changes, and epithelial transcriptome responses. As a control for microbiome stability, 30 non-cancer subjects were longitudinally assessed. Through complementary in vitro assays, we also evaluated the antibacterial potential of 5-FU on oral microorganisms and the interaction of commensals with oral epithelial tissues.ResultsOral mucositis severity was associated with 5-FU, increased salivary flow, and higher oral granulocyte counts. The oral bacteriome was disrupted during chemotherapy and while antibiotic and acid inhibitor intake contributed to these changes, bacteriome disruptions were also correlated with antineoplastics and independently and strongly associated with oral mucositis severity. Mucositis-associated bacteriome shifts included depletion of common health-associated commensals from the genera Streptococcus, Actinomyces, Gemella, Granulicatella, and Veillonella and enrichment of Gram-negative bacteria such as Fusobacterium nucleatum and Prevotella oris. Shifts could not be explained by a direct antibacterial effect of 5-FU, but rather resembled the inflammation-associated dysbiotic shifts seen in other oral conditions. Epithelial transcriptional responses during chemotherapy included upregulation of genes involved in innate immunity and apoptosis. Using a multilayer epithelial construct, we show mucositis-associated dysbiotic shifts may contribute to aggravate mucosal damage since the mucositis-depleted Streptococcus salivarius was tolerated as a commensal, while the mucositis-enriched F. nucleatum displayed pro-inflammatory and pro-apoptotic capacity.ConclusionsAltogether, our work reveals that chemotherapy-induced oral mucositis is associated with bacterial dysbiosis and demonstrates the potential for dysbiotic shifts to aggravate antineoplastic-induced epithelial injury. These findings suggest that control of oral bacterial dysbiosis could represent a novel preventive approach to ameliorate oral mucositis.
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Project description:Inflammatory bowel diseases (IBDs) are chronic, idiopathic, relapsing disorders of unclear etiology affecting millions of people worldwide. Aberrant interactions between the human microbiota and immune system in genetically susceptible populations underlie IBD pathogenesis. Despite extensive studies examining the involvement of the gut microbiota in IBD using culture-independent techniques, information is lacking regarding other human microbiome components relevant to IBD. Since accumulated knowledge has underscored the role of the oral microbiota in various systemic diseases, we hypothesized that dissonant oral microbial structure, composition, and function, and different community ecotypes are associated with IBD; and we explored potentially available oral indicators for predicting diseases. We examined the 16S rRNA V3-V4 region of salivary bacterial DNA from 54 ulcerative colitis (UC), 13 Crohn's disease (CD), and 25 healthy individuals using Illumina sequencing. Distinctive sample clusters were driven by disease or health based on principal coordinate analysis (PCoA) of both the Operational Taxonomic Unit profile and Kyoto Encyclopedia of Genes and Genomes pathways. Comparisons of taxa abundances revealed enrichment of Streptococcaceae (Streptococcus) and Enterobacteriaceae in UC and Veillonellaceae (Veillonella) in CD, accompanied by depletion of Lachnospiraceae and [Prevotella] in UC and Neisseriaceae (Neisseria) and Haemophilus in CD, most of which have been demonstrated to exhibit the same variation tendencies in the gut of IBD patients. IBD-related oral microorganisms were associated with white blood cells, reduced basic metabolic processes, and increased biosynthesis and transport of substances facilitating oxidative stress and virulence. Furthermore, UC and CD communities showed robust sub-ecotypes that were not demographic or severity-specific, suggesting their value for future applications in precision medicine. Additionally, indicator species analysis revealed several genera indicative of UC and CD, which were confirmed in a longitudinal cohort. Collectively, this study demonstrates evident salivary dysbiosis and different ecotypes in IBD communities and provides an option for identifying at-risk populations, not only enhancing our understanding of the IBD microbiome apart from the gut but also offering a clinically useful strategy to track IBD as saliva can be sampled conveniently and non-invasively.
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Project description:Background: The differential abundance of cell-free RNAs in bodily fluids is emerging as a promising tool for the non-invasive molecular diagnosis of cancer. Human saliva is considered a promising source of non-invasive biomarkers of diagnostic value for oral cancer detection. This study aims to identify diagnostic potent salivary RNAs in oral squamous cell carcinoma (OSCC)-patients by RNA-Sequencing. Method: Unstimulated saliva was collected from 5 normal control (NC) individuals and 9 OSCC patients (PS) with prior consent and ethical committee approvals. Total RNA isolated from cell-free saliva (CFS) supernatant was used to prepare small RNA libraries and sequenced on the Ion Torrent S5 platform. The sequencing reads were aligned to the human genome (hg19) using Bowtie 2, and the differential expression analysis was performed using RUVSeq and DESeq2. Mapped reads were screened across miRBase (v22) annotations for miRNAs and Gencode (v19) annotation for other RNAs. Reads were quantified by the Featurecount (v1.4.6) module of the R-package. The microbial-RNA enrichment analysis was determined using the One Codex platform. Result: RNA-sequencing detected protein-coding transcripts (PCTs), long-intergenic RNAs (lincRNAs), microRNAs (miRNAs), small nuclear RNAs (snRNAs), transfer RNAs (tRNAs) and pseudogenes from the saliva of PS and HC samples. Transcriptome analyses revealed 89 PCTs, 18 lincRNAs and 6 miRNAs differentially expressed between PS and HC with a log2fold change ≥ 1 or ≤ -1 and p-value < 0.05. Gene ontology and pathway enrichment analyses indicated a significant correlation of the identified PCTs and miRNAs to various cancer-related pathways that may have implications in the pathogenesis of OSCC. Interestingly, unmapped non-human reads aligned to the microbial reference genomes. Further analyses of these microbial sequence reads revealed a significant microbial dysbiosis differentiating PS from HC. Metabolic pathways and functional analysis of the identified microbial phylotypes showed gene ontologies associated with inflammation, cell proliferation, ROS generation, and a range of metabolic processes. Conclusion: We report novel panels of differentially expressed PCTs, miRNAs and lincRNAs distinguishing PS from HC. Importantly, our results also provide evidence for oral microbial dysbiosis that appears to have pathological implications in OSCC. Summarily, this study provides a comprehensive landscape of salivary RNAs that can be exploited as non-invasive biomarkers for OSCC detection.
2023-01-30 | GSE176077 | GEO
Project description:Objective: While some oral carcinomas appear to arise de novo, others develop within long-standing conditions of the oral cavity that have malignant potential, now known as oral potentially malignant disorders (OPMDs). The oral bacteriome associated with OPMD has been studied to a lesser extent than that associated with oral cancer. To characterize the association in detail we compared the bacteriome in whole mouth fluid (WMF) in patients with oral leukoplakia, oral cancer and healthy controls. Methods: WMF bacteriome from 20 leukoplakia patients, 31 patients with oral cancer and 23 healthy controls were profiled using the Illumina MiSeq platform. Sequencing reads were processed using DADA2, and taxonomical classification was performed using the phylogenetic placement method. Sparse Partial Least Squares Regression Discriminant Analysis model was used to identify bacterial taxa that best discriminate the studied groups. Results: We found considerable overlap between the WMF bacteriome of leukoplakia and oral cancer while a clearer separation between healthy controls and the former two disorders was observed. Specifically, the separation was attributed to 14 taxa belonging to the genera Megaspheara, unclassified enterobacteria, Prevotella, Porphyromonas, Rothia and Salmonella, Streptococcus, and Fusobacterium. The most discriminative bacterial genera between leukoplakia and oral cancer were Megasphaera, unclassified Enterobacteriae, Salmonella and Prevotella. Conclusion: Oral bacteria may play a role in the early stages of oral carcinogenesis as a dysbiotic bacteriome is associated with oral leukoplakia and this resembles that of oral cancer more than healthy controls. Our findings may have implications for developing oral cancer prevention strategies targeting early microbial drivers of oral carcinogenesis.
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