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Journal of Oral Science 2017In this brief review, we discuss our previous research on the relationship between the bacterial composition of salivary microbiota and periodontal disease. Analysis... (Review)
Review
In this brief review, we discuss our previous research on the relationship between the bacterial composition of salivary microbiota and periodontal disease. Analysis using a terminal restriction fragment length polymorphism method and an international comparison suggest that the predominance of the genera Prevotella and Veillonella in the salivary microbiota is attributable to periodontal disease conditions, and that the predominance of the genus Neisseria indicates healthy periodontal conditions. Furthermore, we recently used next-generation sequencing technology to perform a detailed large-scale analysis of the salivary microbiota. An important finding of that study was that high bacterial richness in the salivary microbiota was significantly associated with poor oral health, as indicated by decayed teeth, periodontitis, and poor oral hygiene. Another important result was that relative abundance of predominant bacteria in saliva was significantly associated with oral health-related conditions. Of the two different cohabiting groups of bacteria found in the salivary microbiota, a greater relative abundance of group I bacteria, which include Prevotella and Veillonella species, was associated with poor oral health, high body mass index, and old age. These findings suggest that the salivary microbiota reflects oral and systemic conditions.
Topics: Bacteria; Humans; Microbiota; Mouth; Periodontal Diseases; RNA, Ribosomal, 16S; Saliva
PubMed: 28637979
DOI: 10.2334/josnusd.16-0856 -
Nature Medicine Jul 2019The human gut microbiome is linked to many states of human health and disease. The metabolic repertoire of the gut microbiome is vast, but the health implications of...
The human gut microbiome is linked to many states of human health and disease. The metabolic repertoire of the gut microbiome is vast, but the health implications of these bacterial pathways are poorly understood. In this study, we identify a link between members of the genus Veillonella and exercise performance. We observed an increase in Veillonella relative abundance in marathon runners postmarathon and isolated a strain of Veillonella atypica from stool samples. Inoculation of this strain into mice significantly increased exhaustive treadmill run time. Veillonella utilize lactate as their sole carbon source, which prompted us to perform a shotgun metagenomic analysis in a cohort of elite athletes, finding that every gene in a major pathway metabolizing lactate to propionate is at higher relative abundance postexercise. Using C-labeled lactate in mice, we demonstrate that serum lactate crosses the epithelial barrier into the lumen of the gut. We also show that intrarectal instillation of propionate is sufficient to reproduce the increased treadmill run time performance observed with V. atypica gavage. Taken together, these studies reveal that V. atypica improves run time via its metabolic conversion of exercise-induced lactate into propionate, thereby identifying a natural, microbiome-encoded enzymatic process that enhances athletic performance.
Topics: Animals; Athletes; Exercise; Gastrointestinal Microbiome; Humans; Lactic Acid; Metagenomics; Mice; Mice, Inbred C57BL; Propionates; Running; Veillonella
PubMed: 31235964
DOI: 10.1038/s41591-019-0485-4 -
Gut Mar 2020Pre-eclampsia (PE) is one of the malignant metabolic diseases that complicate pregnancy. Gut dysbiosis has been identified for causing metabolic diseases, but the role...
OBJECTIVE
Pre-eclampsia (PE) is one of the malignant metabolic diseases that complicate pregnancy. Gut dysbiosis has been identified for causing metabolic diseases, but the role of gut microbiome in the pathogenesis of PE remains unknown.
DESIGN
We performed a case-control study to compare the faecal microbiome of PE and normotensive pregnant women by 16S ribosomal RNA (rRNA) sequencing. To address the causative relationship between gut dysbiosis and PE, we used faecal microbiota transplantation (FMT) in an antibiotic-treated mouse model. Finally, we determined the microbiome translocation and immune responses in human and mouse placental samples by 16S rRNA sequencing, quantitative PCR and in situ hybridisation.
RESULTS
Patients with PE showed reduced bacterial diversity with obvious dysbiosis. Opportunistic pathogens, particularly and , were enriched, whereas beneficial bacteria, including and , were markedly depleted in the PE group. The abundances of these discriminative bacteria were correlated with blood pressure (BP), proteinuria, aminotransferase and creatinine levels. On successful colonisation, the gut microbiome from patients with PE triggered a dramatic, increased pregestational BP of recipient mice, which further increased after gestation. In addition, the PE-transplanted group showed increased proteinuria, embryonic resorption and lower fetal and placental weights. Their T regulatory/helper-17 balance in the small intestine and spleen was disturbed with more severe intestinal leakage. In the placenta of both patients with PE and PE-FMT mice, the total bacteria, , and inflammatory cytokine levels were significantly increased.
CONCLUSIONS
This study suggests that the gut microbiome of patients with PE is dysbiotic and contributes to disease pathogenesis.
Topics: Animals; Bacterial Translocation; Blood Pressure; CD4 Lymphocyte Count; Case-Control Studies; Chemokines; Creatinine; Cytokines; Disease Models, Animal; Dysbiosis; Faecalibacterium; Feces; Female; Fetal Resorption; Fusobacteria; Gastrointestinal Microbiome; Humans; Intestine, Small; Mice; Placenta; Pre-Eclampsia; Pregnancy; Proteinuria; RNA, Messenger; T-Lymphocytes, Regulatory; Th17 Cells; Veillonella
PubMed: 31900289
DOI: 10.1136/gutjnl-2019-319101 -
Frontiers in Cellular and Infection... 2021Graves' disease (GD) is a clinical syndrome with an enlarged and overactive thyroid gland, an accelerated heart rate, Graves' orbitopathy (GO), and pretibial myxedema... (Review)
Review
Graves' disease (GD) is a clinical syndrome with an enlarged and overactive thyroid gland, an accelerated heart rate, Graves' orbitopathy (GO), and pretibial myxedema (PTM). GO is the most common extrathyroidal complication of GD. GD/GO has a significant negative impact on the quality of life. GD is the most common systemic autoimmune disorder, mediated by autoantibodies to the thyroid-stimulating hormone receptor (TSHR). It is generally accepted that GD/GO results from complex interactions between genetic and environmental factors that lead to the loss of immune tolerance to thyroid antigens. However, the exact mechanism is still elusive. Systematic investigations into GD/GO animal models and clinical patients have provided important new insight into these disorders during the past 4 years. These studies suggested that gut microbiota may play an essential role in the pathogenesis of GD/GO. Antibiotic vancomycin can reduce disease severity, but fecal material transfer (FMT) from GD/GO patients exaggerates the disease in GD/GO mouse models. There are significant differences in microbiota composition between GD/GO patients and healthy controls. , , and often increase in GD patients. The commonly used therapeutic agents for GD/GO can also affect the gut microbiota. Antigenic mimicry and the imbalance of T helper 17 cells (Th17)/regulatory T cells (Tregs) are the primary mechanisms proposed for dysbiosis in GD/GO. Interventions including antibiotics, probiotics, and diet modification that modulate the gut microbiota have been actively investigated in preclinical models and, to some extent, in clinical settings, such as probiotics () and selenium supplements. Future studies will reveal molecular pathways linking gut and thyroid functions and how they impact orbital autoimmunity. Microbiota-targeting therapeutics will likely be an essential strategy in managing GD/GO in the coming years.
Topics: Animals; Gastrointestinal Microbiome; Graves Disease; Graves Ophthalmopathy; Humans; Mice; Quality of Life; Receptors, Thyrotropin
PubMed: 35004341
DOI: 10.3389/fcimb.2021.739707 -
Journal of Advanced Research Jan 2023Considerable evidence has linked periodontitis (PD) to hypertension (HTN), but the nature behind this connection is unclear. Dysbiosis of oral microbiota leading to PD...
INTRODUCTION
Considerable evidence has linked periodontitis (PD) to hypertension (HTN), but the nature behind this connection is unclear. Dysbiosis of oral microbiota leading to PD is known to aggravate different systematic diseases, but the alteration of oral microbiota in HTN and their impacts on blood pressure (BP) remains to be discovered.
OBJECTIVES
To characterize the alterations of oral and gut microbiota and their roles in HTN.
METHODS
We performed a cross-sectional (95 HTN participants and 39 controls) and a 6-month follow-up study (52 HTN participants and 26 controls) to analyze the roles of oral and gut microbiota in HTN. Saliva, subgingival plaques, and feces were collected for 16S rRNA gene sequencing or metagenomic analysis. C57BL/6J mice were pretreated with antibiotics to deplete gut microbiota, and then transplanted with human saliva by gavage to test the impacts of abnormal oral-gut microbial transmission on HTN.
RESULTS
BP in participants with PD was higher than no PD in both cross-sectional and follow-up cohort. Relative abundances of 14 salivary genera, 15 subgingival genera and 10 gut genera significantly altered in HTN and those of 7 salivary genera, 12 subgingival genera and 6 gut genera significantly correlated with BP. Sixteen species under 5 genera were identified as oral-gut transmitters, illustrating the presence of oral-gut microbial transmission in HTN. Veillonella was a frequent oral-gut transmitter stably enriched in HTN participants of both cross-sectional and follow-up cohorts. Saliva from HTN participants increased BP in hypertensive mice. Human saliva-derived Veillonella successfully colonized in mouse gut, more abundantly under HTN condition.
CONCLUSIONS
PD and oral microbiota are strongly associated with HTN, likely through oral-gut transmission of microbes. Ectopic colonization of saliva-derived Veillonella in the gut may aggravate HTN. Therefore, precise manipulations of oral microbiota and/or oral-gut microbial transmission may be useful strategies for better prevention and treatment of HTN.
Topics: Humans; Animals; Mice; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Cross-Sectional Studies; Follow-Up Studies; Mice, Inbred C57BL; Microbiota; Hypertension; Periodontitis
PubMed: 36585105
DOI: 10.1016/j.jare.2022.03.007 -
Nature Microbiology Oct 2022Colonization of the intestine by oral microbes has been linked to multiple diseases such as inflammatory bowel disease and colon cancer, yet mechanisms allowing...
Colonization of the intestine by oral microbes has been linked to multiple diseases such as inflammatory bowel disease and colon cancer, yet mechanisms allowing expansion in this niche remain largely unknown. Veillonella parvula, an asaccharolytic, anaerobic, oral microbe that derives energy from organic acids, increases in abundance in the intestine of patients with inflammatory bowel disease. Here we show that nitrate, a signature metabolite of inflammation, allows V. parvula to transition from fermentation to anaerobic respiration. Nitrate respiration, through the narGHJI operon, boosted Veillonella growth on organic acids and also modulated its metabolic repertoire, allowing it to use amino acids and peptides as carbon sources. This metabolic shift was accompanied by changes in carbon metabolism and ATP production pathways. Nitrate respiration was fundamental for ectopic colonization in a mouse model of colitis, because a V. parvula narG deletion mutant colonized significantly less than a wild-type strain during inflammation. These results suggest that V. parvula harness conditions present during inflammation to colonize in the intestine.
Topics: Adenosine Triphosphate; Amino Acids; Animals; Carbon; Inflammation; Inflammatory Bowel Diseases; Intestines; Mice; Nitrates; Veillonella
PubMed: 36138166
DOI: 10.1038/s41564-022-01224-7 -
Gut Aug 2020Recent evidence points to the gut microbiome's involvement in postoperative outcomes, including after gastrectomy. Here, we investigated the influence of gastrectomy for...
OBJECTIVE
Recent evidence points to the gut microbiome's involvement in postoperative outcomes, including after gastrectomy. Here, we investigated the influence of gastrectomy for gastric cancer on the gut microbiome and metabolome, and how it related to postgastrectomy conditions.
DESIGN
We performed shotgun metagenomics sequencing and capillary electrophoresis time-of-flight mass spectrometry-based metabolomics analyses on faecal samples collected from participants with a history of gastrectomy for gastric cancer (n=50) and compared them with control participants (n=56).
RESULTS
The gut microbiota in the gastrectomy group showed higher species diversity and richness (p<0.05), together with greater abundance of aerobes, facultative anaerobes and oral microbes. Moreover, bile acids such as genotoxic deoxycholic acid and branched-chain amino acids were differentially abundant between the two groups (linear discriminant analysis (LDA) effect size (LEfSe): p<0.05, q<0.1, LDA>2.0), as were also Kyoto Encyclopedia of Genes and Genomes modules involved in nutrient transport and organic compounds biosynthesis (LEfSe: p<0.05, q<0.1, LDA>2.0).
CONCLUSION
Our results reveal alterations of gut microbiota after gastrectomy, suggesting its association with postoperative comorbidities. The multi-omic approach applied in this study could complement the follow-up of patients after gastrectomy.
Topics: Actinobacteria; Aged; Amino Acids, Branched-Chain; Bacillus; Bacteroidetes; Bifidobacterium; Bile Acids and Salts; Case-Control Studies; Clostridiales; Deoxycholic Acid; Feces; Female; Firmicutes; Gastrectomy; Gastrointestinal Microbiome; Humans; Lactobacillus; Male; Metabolome; Metagenomics; Middle Aged; Prevotella; Sequence Analysis, DNA; Stomach Neoplasms; Streptococcus; Veillonella
PubMed: 31953253
DOI: 10.1136/gutjnl-2019-319188 -
Mediators of Inflammation 2021A very low percentage of lung cancer (LC) cases are discovered at an early and treatable stage of the disease, leading to an abysmally low 5-year survival rate. This... (Review)
Review
A very low percentage of lung cancer (LC) cases are discovered at an early and treatable stage of the disease, leading to an abysmally low 5-year survival rate. This underscores the immediate necessity for improved diagnostic, prognostic, and predictive biomarkers for LC. Biopsied lung tissue, blood, and plasma are common sources used for LC diagnosis and monitoring of the disease. A growing number of studies have reported saliva to be a useful biological sample for early and noninvasive detection of oral and systemic diseases. Nevertheless, salivary biomarker discovery remains underresearched. Here, we have compiled the available literature to provide an overview of the current understanding of salivary markers for LC detection and provided perspectives for future clinical significance. Valuable markers with diagnostic and prognostic potentials in LC have been discovered in saliva, including metabolic (catalase activity, triene conjugates, and Schiff bases), inflammatory (interleukin 10, C-X-C motif chemokine ligand 10), proteomic (haptoglobin, zinc--2-glycoprotein, and calprotectin), genomic (epidermal growth factor receptor), and microbial candidates ( and ). In combination, with each other and with other established screening methods, these salivary markers could be useful for improving early detection of the disease and ultimately improve the survival odds of LC patients. The existing literature suggests that saliva is a promising biological sample for identification and validation of biomarkers in LC, but how saliva can be utilized most effectively in a clinical setting for LC management is still under investigation.
Topics: Biomarkers, Tumor; Gastrointestinal Microbiome; Genomics; Humans; Lung Neoplasms; Proteomics; Saliva
PubMed: 34690552
DOI: 10.1155/2021/6019791 -
Microorganisms Nov 2022Billions of microbes sculpt the gut ecosystem, affecting physiology. Since endurance athletes' performance is often physiology-limited, understanding the composition and...
Billions of microbes sculpt the gut ecosystem, affecting physiology. Since endurance athletes' performance is often physiology-limited, understanding the composition and interactions within athletes' gut microbiota could improve performance. Individual studies describe differences in the relative abundance of bacterial taxa in endurance athletes, suggesting the existence of an "endurance microbiota", yet the taxa identified are mostly non-overlapping. To narrow down the source of this variation, we created a bioinformatics workflow and reanalyzed fecal microbiota from four 16S rRNA gene sequence datasets associated with endurance athletes and controls, examining diversity, relative abundance, correlations, and association networks. There were no significant differences in alpha diversity among all datasets and only one out of four datasets showed a significant overall difference in bacterial community abundance. When bacteria were examined individually, there were no genera with significantly different relative abundance in all four datasets. Two genera were significantly different in two datasets ( and ). No changes in correlated abundances were consistent across datasets. A power analysis using the variance in relative abundance detected in each dataset indicated that much larger sample sizes will be necessary to detect a modest difference in relative abundance especially given the multitude of covariates. Our analysis confirms several challenges when comparing microbiota in general, and indicates that microbes consistently or universally associated with human endurance remain elusive.
PubMed: 36363806
DOI: 10.3390/microorganisms10112213 -
Frontiers in Oral Health 2021The genus comprises 16 characterized species, among which eight are commonly found in the human oral cavity. The high abundance of species in the microbiome of both... (Review)
Review
The genus comprises 16 characterized species, among which eight are commonly found in the human oral cavity. The high abundance of species in the microbiome of both supra- and sub-gingival biofilms, and their interdependent relationship with a multitude of other bacterial species, suggest veillonellae to play an important role in oral biofilm ecology. Development of oral biofilms relies on an incremental coaggregation process between early, bridging and later bacterial colonizers, ultimately forming multispecies communities. As early colonizer and bridging species, veillonellae are critical in guiding the development of multispecies communities in the human oral microenvironment. Their ability to establish mutualistic relationships with other members of the oral microbiome has emerged as a crucial factor that may contribute to health equilibrium. Here, we review the general characteristics, taxonomy, physiology, genomic and genetics of veillonellae, as well as their bridging role in the development of oral biofilms. We further discuss the role of spp. as potential "accessory pathogens" in the human oral cavity, capable of supporting colonization by other, more pathogenic species. The relationship between spp. and dental caries, periodontitis, and peri-implantitis is also recapitulated in this review. We finally highlight areas of future research required to better understand the intergeneric signaling employed by veillonellae during their bridging activities and interspecies mutualism. With the recent discoveries of large species and strain-specific variation within the genus in biological and virulence characteristics, the study of as an example of highly adaptive microorganisms that indirectly participates in dysbiosis holds great promise for broadening our understanding of polymicrobial disease pathogenesis.
PubMed: 35048073
DOI: 10.3389/froh.2021.774115