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Frontiers in Microbiology 2023Gut microbiota plays an important role in colorectal cancer (CRC) pathogenesis through microbes and their metabolites, while oral pathogens are the major components of...
OBJECTIVE
Gut microbiota plays an important role in colorectal cancer (CRC) pathogenesis through microbes and their metabolites, while oral pathogens are the major components of CRC-associated microbes. Multiple studies have identified gut and fecal microbiome-derived biomarkers for precursors lesions of CRC detection. However, few studies have used salivary samples to predict colorectal polyps. Therefore, in order to find new noninvasive colorectal polyp biomarkers, we searched into the differences in fecal and salivary microbiota between patients with colorectal polyps and healthy controls.
METHODS
In this case-control study, we collected salivary and fecal samples from 33 patients with colorectal polyps (CP) and 22 healthy controls (HC) between May 2021 and November 2022. All samples were sequenced using full-length 16S rRNA sequencing and compared with the Nucleotide Sequence Database. The salivary and fecal microbiota signature of colorectal polyps was established by alpha and beta diversity, Linear discriminant analysis Effect Size (LEfSe) and random forest model analysis. In addition, the possibility of microbiota in identifying colorectal polyps was assessed by Receiver Operating Characteristic Curve (ROC).
RESULTS
In comparison to the HC group, the CP group's microbial diversity increased in saliva and decreased in feces ( < 0.05), but there was no significantly difference in microbiota richness ( > 0.05). The principal coordinate analysis revealed significant differences in β-diversity of salivary and fecal microbiota between the CP and HC groups. Moreover, LEfSe analysis at the species level identified and as the major contributors to the salivary microbiota, and and to the fecal microbiota of patients with polyps. Salivary and fecal bacterial biomarkers showed Area Under ROC Curve of 0.8167 and 0.8051, respectively, which determined the potential of diagnostic markers in distinguishing patients with colorectal polyps from controls, and it increased to 0.8217 when salivary and fecal biomarkers were combined.
CONCLUSION
The composition and diversity of the salivary and fecal microbiota were significantly different in colorectal polyp patients compared to healthy controls, with an increased abundance of harmful bacteria and a decreased abundance of beneficial bacteria. A promising non-invasive tool for the detection of colorectal polyps can be provided by potential biomarkers based on the microbiota of the saliva and feces.
PubMed: 37655344
DOI: 10.3389/fmicb.2023.1182346 -
Journal of Dental Research Jul 2023Dental caries lesions are a clinical manifestation of disease, preceded by microbial dysbiosis, which is poorly characterized and thought to be associated with...
Dental caries lesions are a clinical manifestation of disease, preceded by microbial dysbiosis, which is poorly characterized and thought to be associated with saccharolytic taxa. Here, we assessed the associations between the oral microbiome of children and various caries risk factors such as demographics and behavioral and clinical data across early childhood and characterized over time the salivary and dental plaque microbiome of children before clinical diagnosis of caries lesions. Children ( = 266) were examined clinically at ~1, 2.5, 4, and 6.5 y of age. The microbiome samples were collected at 1, 2.5, and 4 y. Caries groups consisted of children who remained caries free (International Caries Detection and Assessment System [ICDAS] = 0) at all time points (CFAT) ( = 50); children diagnosed with caries (ICDAS ≥ 1) at 6.5 y (C6.5), 4 y (C4), or 2.5 y of age (C2.5); and children with early caries or advanced caries lesions at specific time points. Microbial community analyses were performed on zero-radius operational taxonomic units (zOTUs) obtained from V4 of 16S ribosomal RNA gene amplicon sequences. The oral microbiome of the children was affected by various factors, including antibiotic use, demographics, and dietary habits of the children and their caregivers. At all time points, various risk factors explained more of the variation in the dental plaque microbiome than in saliva. At 1 y, composition of saliva of the C4 group differed from that of the CFAT group, while at 2.5 y, this difference was observed only in plaque. At 4 y, multiple salivary and plaque zOTUs of genera and were significantly higher in samples of the C6.5 group than those of the CFAT group. In conclusion, up to 3 y prior to clinical caries detection, the oral microbial communities were already in a state of dysbiosis that was dominated by proteolytic taxa. Plaque discriminated dysbiotic oral ecosystems from healthy ones better than saliva.
Topics: Child; Humans; Child, Preschool; Dental Caries; Dental Plaque; Dysbiosis; Saliva; Microbiota; RNA, Ribosomal, 16S
PubMed: 37042041
DOI: 10.1177/00220345231160756 -
JDR Clinical and Translational Research Oct 2023Common oral diseases are known to be associated with dysbiotic shifts in the supragingival microbiome, yet most oral microbiome associations with clinical end points...
INTRODUCTION
Common oral diseases are known to be associated with dysbiotic shifts in the supragingival microbiome, yet most oral microbiome associations with clinical end points emanate from cross-sectional studies. Orthodontic treatment is an elective procedure that can be exploited to prospectively examine clinically relevant longitudinal changes in the composition and function of the supragingival microbiome.
METHODS
A longitudinal cohort study was conducted among 24 adolescent orthodontic patients who underwent saliva and plaque sampling and clinical examinations at time points: before fixed appliance bonding and at 1, 6, and 12 wk thereafter. Clinical indices included bleeding on probing (BOP), mean gingival index (GI), probing depths (PDs), and plaque index (PI). To study the biologically (i.e., transcriptionally) active microbial communities, RNA was extracted from plaque and saliva for RNA sequencing and microbiome bioinformatics analysis. Longitudinal changes in microbiome beta diversity were examined using PERMANOVA tests, and the relative abundance of microbial taxa was measured using Kruskal-Wallis tests, Wilcoxon rank-sum tests, and negative binomial and zero-inflated mixed models.
RESULTS
Clinical measures of oral health deteriorated over time-the proportion of sites with GI and PI ≥1 increased by over 70% between prebonding and 12 wk postbonding while the proportion of sites with PD ≥4 mm increased 2.5-fold. , a health-associated species that antagonizes cariogenic pathogens, showed a lasting decrease in relative abundance during orthodontic treatment. Contrarily, caries- and periodontal disease-associated taxa, including , , and , increased in abundance after bonding. Relative abundances of and in prebonding saliva predicted elevated BOP 12 wk postbonding, whereas was associated with lower BOP.
CONCLUSIONS
This study offers insights into longitudinal community and species-specific changes in the supragingival microbiome transcriptome during fixed orthodontic treatment, advancing our understanding of microbial dysbioses and identifying targets of future health-promoting clinical investigations.
KNOWLEDGE TRANSFER STATEMENT
Bonding braces was associated with subsequent changes in the oral microbiome characterized by increases in disease-associated species, decreases in health-associated species, and worsened clinical measures of oral health.
PubMed: 37876206
DOI: 10.1177/23800844231199393 -
Journal of Oral Pathology & Medicine :... Nov 2023Oral mucositis (OM) is a severe and common adverse effect of cancer treatment. The oral microbiome appears to play a role on the onset and severity of OM. Therefore,... (Review)
Review
BACKGROUND
Oral mucositis (OM) is a severe and common adverse effect of cancer treatment. The oral microbiome appears to play a role on the onset and severity of OM. Therefore, this systematic review aims to characterize the oral dysbiosis associated with OM.
METHODS
The PRISMA checklist was followed and PubMed, Web of Science, and Scopus were screened for clinical studies characterizing the oral microbiome alterations in patients with OM.
RESULTS
From a total of 2500 articles retrieved, we included nine articles in this systematic review. Certain types of bacteria, as Fusobacterium, were recognized as predictors of the onset of OM. In addition, it was reported that patients with severe OM presented a reduction in alpha-diversity, an increase in beta-diversity. The abundance of some taxa significantly changed with OM severity, with Bacillota phylum and genera Leptotrichia, Actinomyces, and Prevotella decreasing and Treponema increasing with disease progression. Additionally, during cancer treatment, changes in the oral microbiome have been observed in OM patients, with an increase in Candida and nosocomial pathogens, including Staphylococcus species.
CONCLUSION
Our review indicates that cancer treatment can significantly alter the oral microbiome, with more pronounced changes observed in patients with severe OM in all relevant oral phyla, but more pronounced in Bacillota phylum.
Topics: Humans; Stomatitis; Microbiota; Drug-Related Side Effects and Adverse Reactions; Candida; Disease Progression
PubMed: 37839408
DOI: 10.1111/jop.13492 -
Microbiome Nov 2023Oral squamous cell carcinoma (SCC) is associated with oral microbial dysbiosis. In this unique study, we compared pre- to post-treatment salivary microbiome in patients...
BACKGROUND
Oral squamous cell carcinoma (SCC) is associated with oral microbial dysbiosis. In this unique study, we compared pre- to post-treatment salivary microbiome in patients with SCC by 16S rRNA gene sequencing and examined how microbiome changes correlated with the expression of an anti-microbial protein.
RESULTS
Treatment of SCC was associated with a reduction in overall bacterial richness and diversity. There were significant changes in the microbial community structure, including a decrease in the abundance of Porphyromonaceae and Prevotellaceae and an increase in Lactobacillaceae. There were also significant changes in the microbial community structure before and after treatment with chemoradiotherapy, but not with surgery alone. In patients treated with chemoradiotherapy alone, several bacterial populations were differentially abundant between responders and non-responders before and after therapy. Microbiome changes were associated with a change in the expression of DMBT1, an anti-microbial protein in human saliva. Additionally, we found that salivary DMBT1, which increases after treatment, could serve as a post-treatment salivary biomarker that links to microbial changes. Specifically, post-treatment increases in human salivary DMBT1 correlated with increased abundance of Gemella spp., Pasteurellaceae spp., Lactobacillus spp., and Oribacterium spp. This is the first longitudinal study to investigate treatment-associated changes (chemoradiotherapy and surgery) in the oral microbiome in patients with SCC along with changes in expression of an anti-microbial protein in saliva.
CONCLUSIONS
The composition of the oral microbiota may predict treatment responses; salivary DMBT1 may have a role in modulating the oral microbiome in patients with SCC. After completion of treatment, 6 months after diagnosis, patients had a less diverse and less rich oral microbiome. Leptotrichia was a highly prevalent bacteria genus associated with disease. Expression of DMBT1 was higher after treatment and associated with microbiome changes, the most prominent genus being Gemella Video Abstract.
Topics: Humans; Mouth Neoplasms; Longitudinal Studies; Carcinoma, Squamous Cell; RNA, Ribosomal, 16S; Microbiota; Saliva; Bacteria; Calcium-Binding Proteins; DNA-Binding Proteins; Tumor Suppressor Proteins
PubMed: 38037123
DOI: 10.1186/s40168-023-01677-w -
Frontiers in Oncology 2023Head and neck cancer (HNC) is the sixth most common type of cancer, with more than half a million new cases annually. This review focuses on the role of oral dysbiosis... (Review)
Review
Head and neck cancer (HNC) is the sixth most common type of cancer, with more than half a million new cases annually. This review focuses on the role of oral dysbiosis and HPV infection in HNCs, presenting the involved taxons, molecular effectors and pathways, as well as the HPV-associated particularities of genetic and epigenetic changes and of the tumor microenvironment occurred in different stages of tumor development. Oral dysbiosis is associated with the evolution of HNCs, through multiple mechanisms such as inflammation, genotoxins release, modulation of the innate and acquired immune response, carcinogens and anticarcinogens production, generation of oxidative stress, induction of mutations. Thus, novel microbiome-derived biomarkers and interventions could significantly contribute to achieving the desideratum of personalized management of oncologic patients, regarding both early diagnosis and treatment. The results reported by different studies are not always congruent regarding the variations in the abundance of different taxons in HNCs. However, there is a consistent reporting of a higher abundance of Gram-negative species such as , which are probably responsible of chronic inflammation and modulation of tumor microenvironment. is the dominant fungi found in oral carcinoma being also associated with shorter survival rate. Specific microbial signatures (e.g., and ) have been associated with later stages and larger tumor, suggesting their potential to be used as biomarkers for tumor stratification and prognosis. On the other hand, increased abundance of is associated with a reduced risk of HNC. Microbiome could also provide biomarkers for differentiating between oropharyngeal and hypopharyngeal cancers as well as between HPV-positive and HPV-negative tumors. Ongoing clinical trials aim to validate non-invasive tests for microbiome-derived biomarkers detection in oral and throat cancers, especially within high-risk populations. Oro-pharyngeal dysbiosis could also impact the HNCs therapy and associated side-effects of radiotherapy, chemotherapy, and immunotherapy. HPV-positive tumors harbor fewer mutations, as well as different DNA methylation pattern and tumor microenvironment. Therefore, elucidation of the molecular mechanisms by which oral microbiota and HPV infection influence the HNC initiation and progression, screening for HPV infection and vaccination against HPV, adopting a good oral hygiene, and preventing oral dysbiosis are important tools for advancing in the battle with this public health global challenge.
PubMed: 38179168
DOI: 10.3389/fonc.2023.1273516 -
Journal of Clinical Periodontology Jul 2023To evaluate the microbial colonization in different dentition phases on individuals from 0 to 18 years of age belonging to families with a history of periodontitis...
AIM
To evaluate the microbial colonization in different dentition phases on individuals from 0 to 18 years of age belonging to families with a history of periodontitis compared to descendants of periodontally healthy parents.
MATERIALS AND METHODS
The offspring of subjects with periodontitis ('Perio' group) and the offspring of periodontally healthy subjects ('Healthy' group), matched for gender and age, were included in this cross-sectional study and divided according to the dentition phase: pre-dentate, primary, mixed and permanent. The patients were clinically assessed, and their saliva was collected. DNA was extracted, and V1-V3 and V4-V5 regions of the 16S rRNA gene were sequenced.
RESULTS
Fifty children of parents with periodontitis and 50 from healthy parents were included in the study and divided according to the dentition phase: pre-dentate (n = 5/group), primary dentition (n = 15/group), mixed dentition (n = 15/group) and permanent dentition (n = 15/group) in each group. The microbiome composition was different between dentitions for both groups. Children of the Perio group presented a microbial diversity different from that of the Healthy group in mixed and permanent dentitions. The more intense shift in the community occurred between primary and mixed dentition in the Perio group, while the transition between mixed and permanent dentition was the period with greater changes in the microbiome for the Healthy group. Furthermore, a pathogen-rich environment-higher prevalence and abundance of periodontitis-associated species such as Prevotella spp., Selenomonas spp., Leptotrichia spp., Filifactor alocis, Prevotella intermedia, Treponema denticola and Tannerella forsythia- was observed in the Perio group.
CONCLUSIONS
The parents' periodontal status significantly affects the microbiome composition of their offspring from an early age. The mixed dentition was the phase associated with establishing a dysbiotic and pathogen-rich microbiome in descendants of parents with periodontitis.
Topics: Child; Humans; RNA, Ribosomal, 16S; Cross-Sectional Studies; Periodontitis; Microbiota; Parents; Dysbiosis
PubMed: 37086047
DOI: 10.1111/jcpe.13815 -
International Journal of Molecular... Oct 2023The tumor microbiome, a relatively new research field, affects tumor progression through several mechanisms. The Cancer Microbiome Atlas (TCMA) database was recently...
The tumor microbiome, a relatively new research field, affects tumor progression through several mechanisms. The Cancer Microbiome Atlas (TCMA) database was recently published. In the present study, we used TCMA and The Cancer Genome Atlas and examined microbiome profiling in head and neck squamous cell carcinoma (HNSCC), the role of the intratumoral microbiota in the prognosis of HNSCC patients, and differentially expressed genes in tumor cells in relation to specific bacterial infections. We investigated 18 microbes at the genus level that differed between solid normal tissue ( = 22) and primary tumors ( = 154). The tissue microbiome profiles of , , and at the genus level differed between the solid normal tissue and primary tumors of HNSCC patients. When the prognosis of groups with rates over and under the median for each microbe at the genus level was examined, rates for which were over the median correlated with significantly higher overall survival rates. We then extracted 35 differentially expressed genes between the over- and under-the-median-for groups based on the criteria of >1.5 fold and < 0.05 in the Mann-Whitney U-test. A pathway analysis showed that these -related genes were associated with the pathways of Alzheimer disease, neurodegeneration-multiple diseases, prion disease, MAPK signaling, and PI3K-Akt signaling, while protein-protein interaction analysis revealed that these genes formed a dense network. In conclusion, probiotics and specific antimicrobial therapy targeting may have an impact on the prognosis of HNSCC.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Phosphatidylinositol 3-Kinases; Head and Neck Neoplasms; Signal Transduction; Microbiota; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic
PubMed: 37895136
DOI: 10.3390/ijms242015456 -
Microbiology Spectrum Jun 2023Inappropriate antibiotic prescriptions are common for patients with upper respiratory tract infections (URTIs). Few data exist regarding the effects of antibiotic... (Randomized Controlled Trial)
Randomized Controlled Trial
Azithromycin Exposure Induces Transient Microbial Composition Shifts and Decreases the Airway Microbiota Resilience from Outdoor PM Stress in Healthy Adults: a Randomized, Double-Blind, Placebo-Controlled Trial.
Inappropriate antibiotic prescriptions are common for patients with upper respiratory tract infections (URTIs). Few data exist regarding the effects of antibiotic administration on airway microbiota among healthy adults. We conducted a randomized, double-blind, placebo-controlled trial to characterize the airway microbiota longitudinally in healthy adults using 16S rRNA gene sequencing and quantification. Both the induced sputum and oral wash samples were collected over a 60-day period following a 3-day intervention with 500 mg azithromycin or placebo. Environmental information, including air quality data (particulate matter [PM] and PM, air quality index [AQI] values), were also collected during the study. A total of 48 healthy volunteers were enrolled and randomly assigned into two groups. Azithromycin did not alter bacterial load but significantly reduced species richness and Shannon index. Azithromycin exposure resulted in a decrease in the detection rate and relative abundance of different genera belonging to , Leptotrichia, Fusobacterium, Neisseria, and Haemophilus. In contrast, the relative abundance of taxa belonging to Streptococcus increased immediately after azithromycin intervention. The shifts in the diversity of the microbiology composition took between 14 and 60 days to recover, depending on the measure used: either UniFrac phylogenetic distance or α-diversity. Outdoor environmental perturbations, especially the high concentration of PM, contributed to novel variability in microbial community composition of the azithromycin group at D30 (30 days after baseline). The network analysis found that azithromycin altered the microbial interactions within airway microbiota. The influence was still obvious at D14 when the relative abundance of most taxa had returned to the baseline level. Compared to the sputum microbiota, oral cavity microbiota had a different pattern of change over time. The induced sputum microbial data can represent the airway microbiota composition in healthy adults. Azithromycin may have transient effects in the airway microbiota of healthy adults and decrease the airway microbiota resilience against outdoor environmental stress. The influence of azithromycin on microbial interactions is noteworthy, although the airway microbiota has returned to a near-baseline level. The influence of antibiotic administration on the airway microbiota of healthy adults remains unknown. This study is a randomized, double-blind, placebo-controlled trial aiming to investigate the microbial shifts in airways after exposure to azithromycin among heathy adults. We find that azithromycin changes the airway microbial community composition of healthy adults and decreases the airway microbiota resilience against outdoor environmental stress. This study depicts the longitudinal recovery trajectory of airway microbiota after the antibiotic perturbation and may provide reference for appropriate antibiotic prescription.
Topics: Humans; Adult; Azithromycin; Phylogeny; RNA, Ribosomal, 16S; Anti-Bacterial Agents; Microbiota; Particulate Matter
PubMed: 37093053
DOI: 10.1128/spectrum.02066-22 -
Sleep & Breathing = Schlaf & Atmung Aug 2023The oral microbiota is closely associated with systemic health, but few studies have investigated the oral microbiota in patients with obstructive sleep apnea (OSA)....
PURPOSE
The oral microbiota is closely associated with systemic health, but few studies have investigated the oral microbiota in patients with obstructive sleep apnea (OSA). This study aimed to identify the variation of oral microbiota among patients with severe OSA, and the change of oral microbiota after treatment with continuous positive airway pressure (CPAP).
METHODS
Participants were enrolled in the study from November 2020 to August 2021. Sleep parameters using full nocturnal polysomnography (PSG) were collected on healthy controls, patients with severe OSA, and patients with severe OSA after CPAP treatment for 3 months. Oral samples were also collected by rubbing disposable medical sterile swabs on the buccal mucosa. Routine blood tests and biochemical indicators were measured using the fully automated biochemical analyzer. Oral microbial composition of oral samples were determined using whole-genome metagenomic analysis in all participants. Correlations were analyzed between the oral microbiota and blood lipids.
RESULTS
Study enrollment included 14 participants, 7 healthy controls and 7 patients with severe OSA. At the species level, the relative abundances of Prevotella, Alloprevotella, Bacteroides, Veillonella_tobetsuensis, Candidatus saccharimonas, and Leptotrichia in the groups with severe OSA were significantly lower than those in the healthy controls (P both < 0.05). The abundances of Capnocytophaga, Veillonella, Bacillus_anthracis, Eikenella, and Kingella were significantly higher whereas the abundances of Gordonia and Streptococcus were significantly lower in the group with severe OSA compared to the severe OSA-CPAP group (P < 0.05 for both). According to the Kyoto Encyclopedia of Genes and Genomes (KEGG), 4 pathways changed in the group with severe OSA compared with healthy controls (P both < 0.05). Pathways related to Novobiocin biosynthesis, 2-Oxocarboxylic acid metabolism, and Histidine metabolism were enriched in the patients with severe OSA. Nine pathways showed significant differences with regard to the relative abundances of phenylalanine metabolism; alanine, aspartate, and glutamate metabolism; one carbon pool by folate; monobactam biosynthesis; 2-oxocarboxylic acid metabolism; arginine biosynthesis and vitamin B6 metabolism; novobiocin biosynthesis; and arginine and proline metabolism, which were significantly higher in the group with severe OSA compared to the severe OSA-CPAP group (P both < 0.05). The Spearman correlation analysis between blood lipid parameters and oral microbiota components showed that negative correlations were observed between total cholesterol and Streptomyces (r = - 0.893, P = 0.007), and high-density lipoprotein cholesterol (HDL-C) and Gordonia (r = - 0.821, P = 0.023); positive correlations were observed between HDL-C and Candidatus saccharimonas (r = 0.929, P = 0.003), and low-density lipoprotein cholesterol (LDL-C) and Capnocytophaga (r = 0.893, P = 0.007).
CONCLUSION
There was an apparent discrepancy of the oral microbiota and metabolic pathways between the group with severe OSA and controls, and CPAP significantly changed oral microbial abundance and metabolic pathways in patients with severe OSA. Correlation analysis showed that these oral bacteria were strongly correlated with the blood lipids level.
Topics: Humans; Novobiocin; Sleep Apnea, Obstructive; Cholesterol, LDL; Lipids; Continuous Positive Airway Pressure; Microbiota
PubMed: 36401059
DOI: 10.1007/s11325-022-02732-w