Alterations in the human oral microbiome in cholangiocarcinoma

Dear Editor,Alterations in the human microbiome are closely related to various hepatobiliary diseases.Gut microbial dysbiosis has been found in patients with cholangiocarcinoma(CCA)[1].However,the characteristics of oral microbiome in patients with CCA have not been studied.

Oral microbiome and risk of malignant esophageal lesions in a high-risk area of China:A nested case-control study

Objective:We aimed to prospectively evaluate the association of oral microbiome with malignant esophageal lesions and its predictive potential as a biomarker of risk.Methods:We conducted a case-control study nested within a population-based cohort with up to 8 visits of oral swab collection for each subject over an 11-year period in a high-risk area for esophageal cancer in China.The oral microbiome was evaluated with 16 S ribosomal RNA(rRNA)gene sequencing in 428 pre-diagnostic oral specimens from 84 cases with esophageal lesions of severe squamous dysplasia and above(SDA)and 168 matched healthy controls.DESeq analysis was performed to identify taxa of differential abundance.Differential oral species together with subject characteristics were evaluated for their potential in predicting SDA risk by constructing conditional logistic regression models.Results:A total of 125 taxa including 37 named species showed significantly different abundance between SDA cases and controls(all P<0.05&false discovery rate-adjusted Q<0.10).A multivariate logistic model including 11 SDA lesion-related species and family history of esophageal cancer provided an area under the receiver operating characteristic curve(AUC)of 0.89(95%CI,0.84-0.93).Cross-validation and sensitivity analysis,excluding cases diagnosed within 1 year of collection of the baseline specimen and their matched controls,or restriction to screenendoscopic-detected or clinically diagnosed case-control triads,or using only bacterial data measured at the baseline,yielded AUCs>0.84.Conclusions:The oral microbiome may play an etiological and predictive role in esophageal cancer,and it holds promise as a non-invasive early warning biomarker for risk stratification for esophageal cancer screening programs.

Characterization of oral and gut microbiome and plasma metabolomics in COVID-19 patients after 1-year follow-up

Background:Due to the outbreak and rapid spread of coronavirus disease 2019(COVID-19),more than 160 million patients have become convalescents worldwide to date.Significant alterations have occurred in the gut and oral microbiome and metabonomics of patients with COVID-19.However,it is unknown whether their characteristics return to normal after the 1-year recovery.Methods:We recruited 35 confirmed patients to provide specimens at discharge and 1 year later,as well as 160healthy controls.A total of 497 samples were prospectively collected,including 219 tongue-coating,129 stool and 149 plasma samples.Tongue-coating and stool samples were subjected to 16S rRNA sequencing,and plasma samples were subjected to untargeted metabolomics testing.Results:The oral and gut microbiome and metabolomics characteristics of the 1-year convalescents were restored to a large extent but did not completely return to normal.In the recovery process,the microbial diversity gradually increased.Butyric acid-producing microbes and Bifidobacterium gradually increased,whereas lipopolysaccharideproducing microbes gradually decreased.In addition,sphingosine-1-phosphate,which is closely related to the inflammatory factor storm of COVID-19,increased significantly during the recovery process.Moreover,the predictive models established based on the microbiome and metabolites of patients at the time of discharge reached high efficacy in predicting their neutralizing antibody levels one year later.Conclusions:This study is the first to characterize the oral and gut microbiome and metabonomics in 1-year convalescents of COVID-19.The key microbiome and metabolites in the process of recovery were identified,and provided new treatment ideas for accelerating recovery.And the predictive models based on the microbiome and metabolomics afford new insights for predicting the recovery situation which benefited affected individuals and healthcare.

Oral microbiome: a doubtful predictor butpotential target of cardiovascular diseases

Our oral cavity houses various types of microbesincluding bacteria, protozoa, fungi and viruses, harboringover 700 bacterial species. Oral dysbiosis refers to theimbalance between symbionts and pathobionts in the oralcavity, posing potential threats to host cardiovascularhealth. Importantly, oral dysbiosis promotes cardiovascular pathophysiology through different mechanisms.Although overgrowth of certain pathogenic bacteria havebeen indicated in some cardiometabolic diseases, it is stillpremature to consider oral microbiome as a suitable predictor for non-invasive diagnostic purpose. However, targeting oral microbiome might still provide preventive andtherapeutic insights on cardiovascular diseases. Furtherextensive efforts are needed to deepen our understandingon oral-cardiovascular connection in the context of diagnostic and therapeutic perspectives.

Oral Hygiene in the Presence of Orthodontic Therapy

Orthodontic treatment offers great advantages in improving facial and smile aesthetics, self-confidence and the function of the stomatognathic apparatus. The pursuit of these advantages makes use of orthodontic appliances that could be fixed or removable. However, it’s worth stating that these appliances interfere with tooth brushing, making it more difficult to brush teeth effectively. Orthodontics appliances therefore promote the accumulation of dental plaque, which results in both quantitative and qualitative changes in the oral microbiota, hence, exposing patients to several adverse effects such as White spot lesions, dental caries, periodontal pathologies and halitosis. For this reason, oral assessment of patients before, during and after treatment is necessary as well as oral hygiene instructions and motivation. Orthodontists therefore, should educate patients on oral and periodontal hygiene in order to control dental and periodontal complications. Prescriptions of plaque control materials adapted to each patient are done in order to optimize the final result and minimize unwanted complications.

Oral microbiomes： more and more importance in oral cavity and whole body

Microbes appear in every corner of human life, and microbes affect every aspect of human life. The human oral cavity contains a number of different habitats. Synergy and interaction of variable oral microorganisms help human body against invasion of undesirable stim- ulation outside. However, imbalance of microbial flora contributes to oral diseases and systemic diseases. Oral microbiomes play an important role in the human microbial community and human health. The use of recently developed molecular methods has greatly expanded our knowledge of the composition and function of the oral microbiome in health and disease. Studies in oral microbiomes and their interactions with microbiomes in variable body sites and variable health condition are critical in our cognition of our body and how to make effect on human health improvement.

The oral microbiome of pregnant women facilitates gestational diabetes discrimination

The oral microbiota plays an important role in the development of various diseases,whereas its association with gestational diabetes mellitus (GDM) remains largely unclear.The aim of this study is to identify biomarkers from the oral microbiota of GDM patients by analyzing the microbiome of the saliva and dental plaque samples of 111 pregnant women.We find that the microbiota of both types of oral samples in GDM patients exhibits differences and significantly varies from that of patients with periodontitis or dental caries.Using bacterial biomarkers from the oral microbiota,GDM classification models based on support vector machine and random forest algorithms are constructed.The area under curve (AUC) value of the classification model constructed by combination of Lautropia and Neisseria in dental plaque and Streptococcus in saliva reaches 0.83,and the value achieves a maximum value of 0.89 by adding clinical features.These findings suggest that certain bacteria in either saliva or dental plaque can effectively distinguish women with GDM from healthy pregnant women,which provides evidence of oral microbiome as an informative source for developing noninvasive biomarkers of GDM.

Over 50,000 Metagenomically Assembled Draft Genomes for the Human Oral Microbiome Reveal New Taxa

The oral cavity of each person is home to hundreds of bacterial species.While taxa for oral diseases have been studied using culture-based characterization as well as amplicon sequencing,metagenomic and genomic information remains scarce compared to the fecal microbiome.Here,using metagenomic shotgun data for 3346 oral metagenomic samples together with 808 published samples,we obtain 56,213 metagenome-assembled genomes(MAGs),and more than 64%of the 3589 species-level genome bins(SGBs)contain no publicly available genomes.The resulting genome collection is representative of samples around the world and contains many genomes from candidate phyla radiation(CPR)that lack monoculture.Also,it enables the discovery of new taxa such as a genus Candidatus Bgiplasma within the family Acholeplasmataceae.Large-scale metagenomic data from massive samples also allow the assembly of strains from important oral taxa such as Porphyromonas and Neisseria.The oral microbes encode genes that could potentially metabolize drugs.Apart from these findings,a strongly male-enriched Campylobacter species was identified.Oral samples would be more user-friendly collected than fecal samples and have the potential for disease diagnosis.Thus,these data lay down a genomic framework for future inquiries of the human oral microbiome.

Alterations in the oral microbiome in HIV infection:causes,effects and potential interventions

A massive depletion of CD4+T lymphocytes has been described in early and acute human immunodeficiency virus(HIV)infection,leading to an imbalance between the human microbiome and immune responses.In recent years,a growing interest in the alterations in gut microbiota in HIV infection has led to many studies;however,only few studies have been conducted to explore the importance of oral microbiome in HIV-infected individuals.Evidence has indicated the dysbiosis of oral microbiota in people living with HIV(PLWH).Potential mechanisms might be related to the immunodeficiency in the oral cavity of HIV-infected individuals,including changes in secretory components such as reduced levels of enzymes and proteins in saliva and altered cellular components involved in the reduction and dysfunction of innate and adaptive immune cells.As a result,disrupted oral immunity in HIV-infected individuals leads to an imbalance between the oral microbiome and local immune responses,which may contribute to the development of HIV-related diseases and HIV-associated non-acquired immunodeficiency syndrome comorbidities.Although the introduction of antiretroviral therapy(ART)has led to a significant decrease in occurrence of the opportunistic oral infections in HIV-infected individuals,the dysbiosis in oral microbiome persists.Furthermore,several studies with the aim to investigate the ability of probiotics to regulate the dysbiosis of oral microbiota in HIV-infected individuals are ongoing.However,the effects of ART and probiotics on oral microbiome in HIV-infected individuals remain unclear.In this article,we review the composition of the oral microbiome in healthy and HIV-infected individuals and the possible effect of oral microbiome on HIV-associated oral diseases.We also discuss how ART and probiotics influence the oral microbiome in HIV infection.We believe that a deeper understanding of composition and function of the oral microbiome is critical for the development of effective preventive and therapeutic strategies for HIV infection.

Meeting report: a close look at oral biofilms and microbiomes

The "Biofilms, Microbiomes and Oral Diseases: Challenges and Future Perspectives" symposium jointly organized by Penn Dental Medicine and West China School of Stomatology was held on 30 September 2017 at Penn Wharton China Center(PWCC) in Beijing,China. The topics included the pathogenicity of oral biofilms, novel strategies for the control of biofilm-related diseases, oral microbiome and single-cell approaches, and the link between oral diseases and overall health. Researchers from a number of disciplines, representing institutions from China and Penn Dental Medicine, gathered to discuss advances in our understanding of biofilms, as well as future directions for the control of biofilm-related oral and systemic diseases.

Marginal bone loss around non-submerged implants is associated with salivary microbiome during bone healing

Marginal bone loss during bone healing exists around non-submerged dental implants. The aim of this study was to identify the relationship between different degrees of marginal bone loss during bone healing and the salivary microbiome. One hundred patients were recruited, and marginal bone loss around their implants was measured using cone beam computed tomography during a 3-month healing period. The patients were divided into three groups according to the severity of marginal bone loss.Saliva samples were collected from all subjected and were analysed using 16 SMiSeq sequencing. Although the overall structure of the microbial community was not dramatically altered, the relative abundance of several taxonomic groups noticeably changed. The abundance of species in the phyla Spirochaeta and Synergistetes increased significantly as the bone loss became more severe. Species within the genus Treponema also exhibited increased abundance, whereas Veillonella, Haemophilus and Leptotrichia exhibited reduced abundances, in groups with more bone loss. Porphyromonasgingivalis, Treponemadenticola and Streptococcus intermedius were significantly more abundant in the moderate group and/or severe group. The severity of marginal bone loss around the non-submerged implant was associated with dissimilar taxonomic compositions. An increased severity of marginal bone loss was related to increased proportions of periodontal pathogenic species. These data suggest a potential role of microbes in the progression of marginal bone loss during bone healing.

Microbiome and colorectal carcinogenesis:Linked mechanisms and racial differences

Various studies have shown the interplay between the intestinal microbiome,environmental factors,and genetic changes in colorectal cancer(CRC)development.In this review,we highlight the various gut and oral microbiota associated with CRC and colorectal adenomas,and their proposed molecular mechanisms in relation to the processes of“the hallmarks of cancer”,and differences in microbial diversity and abundance between race/ethnicity.Patients with CRC showed increased levels of Bacteroides,Prevotella,Escherichia coli,enterotoxigenic Bacteroides fragilis,Streptococcus gallolyticus,Enterococcus faecalis,Fusobacterium nucleatum(F.nucleatum)and Clostridium difficile.Higher levels of Bacteroides have been found in African American(AA)compared to Caucasian American(CA)patients.Pro-inflammatory bacteria such as F.nucleatum and Enterobacter species were significantly higher in AAs.Also,AA patients have been shown to have decreased microbial diversity compared to CA patients.Some studies have shown that using microbiome profiles in conjunction with certain risk factors such as age,race and body mass index may help predict healthy colon vs one with adenomas or carcinomas.Periodontitis is one of the most common bacterial infections in humans and is more prevalent in Non-Hispanic-Blacks as compared to Non-Hispanic Whites.This condition causes increased systemic inflammation,immune dysregulation,gut microbiota dysbiosis and thereby possibly influencing colorectal carcinogenesis.Periodontal-associated bacteria such as Fusobacterium,Prevotella,Bacteroides and Porphyromonas have been found in CRC tissues and in feces of CRC patients.Therefore,a deeper understanding of the association between oral and gastrointestinal bacterial profile,in addition to identifying prevalent bacteria in patients with CRC and the differences observed in ethnicity/race,may play a pivotal role in predicting incidence,prognosis,and lead to the development of new treatments.

Correlation of Oral Microbiota With Different Immune Responses to Antiretroviral Therapy in People Living With HIV

Both HIV infection and antiretroviral therapy(ART)affect the oral microbiome.Whether successful treatment with ART in people living with HIV(PLWH),which leads to a significant decline in viral loads and immune reconstitution,is associated with changes in or recovery of the oral microbiome remains unknown.Therefore,we performed a cross-sectional study of 118 PLWH receiving regular ART and 40 healthy controls(HCs).Among the 118 PLWH,18 immunological nonresponders(INRs;<200 CD4^(+)T cells/μL)and 30 immunological responders(IRs;≥500 CD4^(+)T cells/μL)were identified.The oral microbiota composition of all participants was analyzed using 16S rRNA gene sequencing of throat swab samples.Relative abundance of bacterial genera was compared between IRs and INRs,and Pearson correlations between bacterial abundance and peripheral blood immune cell counts were evaluated.The INR group showed lower alpha diversity than the IR and HC groups,which displayed similar alpha diversity.The genera Alloprevotella,Prevotella and Neisseria were more abundant in PLWH than in HCs,whereas the genera Rothia,Streptococcus and Fusobacterium were more abundant in HCs than in PLWH.The genus Rothia was more abundant in the INR group,whereas Prevotella,Alloprevotella,Porphyromonas and Haemophilus were more abundant in the IR group.The genera Rothia and Alloprevotella were negatively and positively associated with CD4^(+)T cell counts,respectively.Thus,an increased abundance of Rothia in the oral microbiome is associated with unfavorable outcomes regarding immune reconstitution in PLWH receiving regular ART,whereas Prevotella,Alloprevotella,Porphyromonas and Haemophilus are associated with favorable outcomes.

Commensal microbiota in the digestive tract:a review of its roles in carcinogenesis and radiotherapy

The human microflora is a complex ecosystem composed of diverse microorganisms mainly distributed in the epidermal and mucosal habitats of the entire body,including the mouth,lung,intestines,skin,and vagina.These microbial communities are involved in many essential functions,such as metabolism,immunity,host nutrition,and diseases.Recent studies have focused on the microbiota associated with cancers,particularly the oral and intestinal microbiota.Radiotherapy,the most effective cytotoxic modality available for solid tumors,contributes to the treatment of cancer patients.Mounting evidence supports that the microbiota plays pivotal roles in the efficacy and prognosis of tumor radiotherapy.Here,we review current research on the microbiota and cancer development,and describe knowledge gaps in the study of radiotherapy and the microbiota.Better understanding of the effects of the microbiome in tumorigenesis and radiotherapy will shed light on future novel prevention and treatment strategies based on modulating the microbiome in cancer patients.

Comparative oral metagenome insight into acute and chronic root canal infections

Background:In the dynamic progression of root canal infections,the resultant change in environmental conditions directs the adaptation of the microbiome in terms of richness,evenness,and diversity.Objective:The goal of this study is to contrast the interradicular bacterial community structures of teeth in acute and chronic stages and investigate potential microorganisms associated with persistent apical periapical infections.Methods:Interradicular samples were collected from 10 teeth in the apical periodontitis group and 10 teeth in the chronic apical periodontitis group.High-throughput next-generation sequencing(NGS)–based microbial identification through the Illumina platform was used to characterize the complex intraradicular microbial communities in acute and chronic root canal infections.Results:Bacteria were the major domain,with a prevalence of>97%(acute cases:98.11%and chronic cases:97.6%)compared to eukaryotes and archaea.Bacterial diversity was relatively higher in acute compared to chronic conditions under 10 and 9 phyla,79 and 64 genera,and 172 and 135 species,respectively.These endodontically infecting bacteria belonged to Firmicutes(47.21%),Bacteroidetes(20.07%),and Proteobacteria(10.72%)in acute conditions,while in the chronic stage,Firmicutes(40.85%),Proteobacteria(27.80%),and Actinobacteria(14.79%)were abundant.The phylum Candidatus Saccharibacteria was exclusively found in acute samples.Spirochaetes and Synergistetes were found predominantly in acute infections compared to chronic infections.Bacillus and Lactobacillus were found in equal and highest abundance under the phylum Firmicutes in both conditions.Conclusion:This study provides information on the differential microbial community present in the apical root canal system of teeth with acute and chronic apical periodontitis and contributes to new approaches or channels for future research on preventive measures and therapeutic protocols during disease progression and treatment.However,functional characterization and detection of antimicrobial resistance in these two clinical conditions can supplement these findings for deciding routine drug treatment for periodontal infections.

Novel biomarkers for hepatocellular carcinoma detection and treatment

Hepatocellular carcinoma(HCC)ranks as the sixth most prevalent malignant tumor globally and is the third leading cause of cancer-related mortality,with its incidence and mortality rates demonstrating a consistent annual increase(1).The primary reason for this occurrence lies in the insidious onset of the disease,leading to late-stage diagnosis in a majority of patients,resulting in limited treatment options and poor efficacy.Consequently,emphasis on prevention and early detection is imperative for enhancing the prognosis of HCC patients.Furthermore,the identification of biomarkers with heightened sensitivity and specificity holds particular significance(2).

Effect of Salivary Antimicrobial Factors on Microbial Composition of Tongue Coating in Patients with Coronary Heart Disease with Phlegm-Stasis Syndrome

Objective: Phlegm-stasis syndrome is one of the most common traditional Chinese medicine(TCM) syndromes and found in 59% of patients with coronary heart disease(CHD) in routine TCM clinical practice in China. One of the diagnostic criteria of phlegm-stasis syndrome is its characteristic white-greasy and thin tongue coating. We have previously reported that different types of tongue coating have different microbiome characteristics that can be used as diagnostic markers. However, the microbial characteristics of tongue coating of CHD patients with phlegm-stasis syndrome, including coating feature and underlying reason of formation, have rarely been reported. Herein, we examined the characteristic microbiome of tongue coating, and discussed the cause of tongue coating formation via salivary proteins in patients with phlegm-stasis syndrome. Methods: We examined white-greasy and thin tongue coatings obtained from 10 patients with CHD having phlegm-stasis syndrome(n = 10), and compared with those of patients with almost no coating – patients with Qi-Yin deficiency syndrome(n = 10) – and healthy controls(n = 10). 16S r RNA sequencing of tongue coating microbiome and isobaric tags for relative and absolute quantitation(i TRAQ)-based quantitative analysis of salivary proteins were used to detect tongue coating and salivary protein separately. Salivary levels of s Ig A, lysozyme, and amylase were detected by ELISA. Results: We identified Candidatus_Saccharimonas and Candidate_division_TM7_norank as the prominent members of tongue coating in patients with CHD having phlegm-stasis syndrome. Salivary proteins involved in biological processes, pentose phosphate pathway, and complement and coagulation cascades were among the differentially expressed proteins identified in patients with CHD having phlegm-stasis syndrome on i TRAQ analysis. Moreover, the formation of microbiota in tongue coating was associated with salivary s Ig A, lysozyme, and saliva flow rate. Conclusions: We explored the characteristics of microbial composition of tongue coating patients with CHD having phlegm-stasis syndrome and identified correlations between salivary proteins and microbiome formation, providing a theoretical and mechanistic basis for tongue coating formation.