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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 -
Gut Microbes 2022Frequently, patients with functional gastrointestinal disorders (FGIDs) report intolerance of wheat products. We compared gastrointestinal symptoms, sensory function,...
The duodenal mucosa associated microbiome, visceral sensory function, immune activation and psychological comorbidities in functional gastrointestinal disorders with and without self-reported non-celiac wheat sensitivity.
Frequently, patients with functional gastrointestinal disorders (FGIDs) report intolerance of wheat products. We compared gastrointestinal symptoms, sensory function, psychiatric comorbidities, gut-homing immune cells, and duodenal mucosa-associated microbiome (d-MAM) in FGID patients and controls with and without self-reported wheat sensitivity (SR-NCWS). We recruited 40 FGID patients and 20 controls referred by GPs for treatment. Gastrointestinal/extraintestinal symptoms, visceral sensory function, psychological comorbidities, and SR-NCWS were assessed in a standardized approach. Peripheral gut homing T-cells (CD4α4β7CCR9/CD8α4β7CCR9) were quantified, and the d-MAM was assessed by DNA sequencing for 46 subjects. Factors of bacterial genera were extracted utilizing factor analysis with varimax rotation and factors univariately associated with FGID or SR-NCWS included in a subsequent multivariate analysis of variance to identify statistically independent discriminators. Anxiety scores (p < .05) and increased symptom responses to a nutrient challenge (p < .05) were univariately associated with FGID. Gut homing T-cells were increased in FGID patients with SR-NCWS compared to other groups (p all <0.05). MANOVA revealed that anxiety (p = .03), visceral sensory function (p = 0.007), and a d-MAM factor comprise members of the , and lineages were significantly (p = .001) associated with FGID, while gut homing CD4α4 β7CCR9 T-cells were associated (p = .002) with SR-NCWS. Compared to controls, patients with and without SR-NCWS show that there are shifts in the amplicon sequence variants within specific bacterial genera between the FGID subgroups (particularly and ) as well as distinct bacterial taxa discriminatory for the two different FGID subtypes. Compared to controls, both FGID patients with and without SR-NCWS have an increased symptom response to a standardized nutrient challenge and increased anxiety scores. The FGID patients with SR-NCWS - as compared to FGID without SR-NCWS (and controls without SR-NCWS) - have increased gut homing T-cells. The d-MAM profiles suggest species and strain-based variations between the two FGID subtypes and in comparison to controls.
Topics: Humans; Wheat Hypersensitivity; Self Report; Gastrointestinal Microbiome; Gastrointestinal Diseases; Intestinal Mucosa; Sensation
PubMed: 36303431
DOI: 10.1080/19490976.2022.2132078 -
Microbiology Spectrum Feb 2022Numerous studies have examined the composition of and factors shaping the oral bacterial microbiota in healthy adults; however, similar studies on the less dominant yet...
Numerous studies have examined the composition of and factors shaping the oral bacterial microbiota in healthy adults; however, similar studies on the less dominant yet ecologically and clinically important fungal microbiota are scarce. In this study, we characterized simultaneously the oral bacterial and fungal microbiomes in a large cohort of systemically healthy Chinese adults by sequencing the bacterial 16S rRNA gene and fungal internal transcribed spacer. We showed that different factors shaped the oral bacterial and fungal microbiomes in healthy adults. Sex and age were associated with the alpha diversity of the healthy oral bacterial microbiome but not that of the fungal microbiome. Age was also a major factor affecting the beta diversity of the oral bacterial microbiome; however, it only exerted a small effect on the oral fungal microbiome when compared with other variables. After controlling for age and sex, the bacterial microbiota structure was most affected by marital status, recent oral conditions and oral hygiene-related factors, whereas the fungal microbiota structure was most affected by education level, fruits and vegetables, and bleeding gums. Bacterial-fungal interactions were limited in the healthy oral microbiota, with the strongest association existing between Pseudomonas sp. and . Several bacterial amplicon sequence variants (ASVs) belonging to Veillonella atypica and the genera , Streptococcus and and fungal ASVs belonging to Candida albicans and the genus were revealed as putative pivotal members of the healthy oral microbiota. Overall, our study has facilitated understanding of the determining factors and cross-kingdom interactions of the healthy human oral microbiome. Numerous studies have examined the bacterial community residing in our oral cavity; however, information on the less dominant yet ecologically and clinically important fungal members is limited. In this study, we characterized simultaneously the oral bacterial and fungal microbial communities in a large cohort of healthy Chinese adults, examined their associations with an array of host factors, and explored potential interactions between the two microbial groups. We showed that different factors shape the diversity and structure of the oral bacterial and fungal microbial communities in healthy adults, with, for instance, sex and age only associated with the diversity of the bacterial community but not that of the fungal community. Besides, we found that bacterial-fungal interactions are limited in the healthy oral cavity. Overall, our study has facilitated understanding of the determining factors and bacterial-fungal interactions of the healthy human oral microbial community.
Topics: Adolescent; Adult; Aged; Bacteria; China; Cohort Studies; Female; Fungi; Healthy Volunteers; Humans; Male; Microbiota; Middle Aged; Mouth; Mycobiome; Phylogeny; Young Adult
PubMed: 35107355
DOI: 10.1128/spectrum.02410-21 -
Journal of Clinical Medicine Aug 2020Halitosis is a common ailment concerning 15% to 60% of the human population. Halitosis can be divided into extra-oral halitosis (EOH) and intra-oral halitosis (IOH). The... (Review)
Review
Halitosis is a common ailment concerning 15% to 60% of the human population. Halitosis can be divided into extra-oral halitosis (EOH) and intra-oral halitosis (IOH). The IOH is formed by volatile compounds, which are produced mainly by anaerobic bacteria. To these odorous substances belong volatile sulfur compounds (VSCs), aromatic compounds, amines, short-chain fatty or organic acids, alcohols, aliphatic compounds, aldehydes, and ketones. The most important VSCs are hydrogen sulfide, dimethyl sulfide, dimethyl disulfide, and methyl mercaptan. VSCs can be toxic for human cells even at low concentrations. The oral bacteria most related to halitosis are spp., spp., spp., spp., spp., spp., spp., spp., spp., spp., spp., , and spp. Most bacteria that cause halitosis are responsible for periodontitis, but they can also affect the development of oral and digestive tract cancers. Malodorous agents responsible for carcinogenesis are hydrogen sulfide and acetaldehyde.
PubMed: 32748883
DOI: 10.3390/jcm9082484 -
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 -
Scientific Reports Jan 2021The effect of oral microbial composition on periodontal health and on systemic health has been, and is being established. The oral microbiome, in turn, can be altered by...
The effect of oral microbial composition on periodontal health and on systemic health has been, and is being established. The oral microbiome, in turn, can be altered by local and systemic diseases and conditions. Gastroesophageal reflux disease (GERD), has been associated with increased acidity in the oral cavity resulting in dental erosion, and controversially a reduced risk of periodontal disease. We hypothesized that presence of GERD was linked to a modified microbial profile in untreated GERD patients and that the use of proton pump inhibitor (PPI) drugs: potent disruptors of gut microbiome, in GERD patients might result in a salivary microbiome that is further distinct. Untreated GERD patients showed multiple differences in salivary microbiome as compared to healthy controls. Taxa found at lower levels related to the presence of GERD not treated by PPI included: Prevotella melaninogenica, Prevotella pallens, Leptotrichia, and Solobacterium moorei and thirteen others. In contrast, GERD patients chronically using PPI showed minimal differences in salivary taxa compared to healthy controls not using PPI.
Topics: Female; Gastroesophageal Reflux; Humans; Male; Microbiota; Middle Aged; Proton Pump Inhibitors; Saliva
PubMed: 33420219
DOI: 10.1038/s41598-020-80170-y -
Frontiers in Cellular and Infection... 2021Autoimmune hepatitis (AIH) is a common cause of liver cirrhosis. To identify the characteristics of the oral microbiome in patients with AIH, we collected 204 saliva... (Randomized Controlled Trial)
Randomized Controlled Trial
Autoimmune hepatitis (AIH) is a common cause of liver cirrhosis. To identify the characteristics of the oral microbiome in patients with AIH, we collected 204 saliva samples including 68 AIH patients and 136 healthy controls and performed microbial MiSeq sequencing after screening. All samples were randomly divided into discovery cohorts (46 AIH and 92 HCs) and validation cohorts (22 AIH and 44 HCs). Moreover, we collected samples of 12 AIH patients from Hangzhou for cross-regional validation. We described the oral microbiome characteristics of AIH patients and established a diagnostic model. In the AIH group, the oral microbiome diversity was significantly increased. The microbial communities remarkably differed between the two groups. Seven genera, mainly and , were dominant in the HC group, while 51 genera, and , were enriched in the AIH group. Notably, we found 23 gene functions, including Membrane Transport, Carbohydrate Metabolism, and Glycerolipid metabolism that were dominant in AIH and 31 gene functions that prevailed in HCs. We further investigated the correlation between the oral microbiome and clinical parameters. The optimal 5 microbial markers were figured out through a random forest model, and the distinguishing potential achieved 99.88% between 46 AIH and 92 HCs in the discovery cohort and 100% in the validation cohort. Importantly, the distinguishing potential reached 95.55% in the cross-regional validation cohort. In conclusion, this study is the first to characterize the oral microbiome in AIH patients and to report the successful establishment of a diagnostic model and the cross-regional validation of microbial markers for AIH. Importantly, oral microbiota-targeted biomarkers may be able to serve as powerful and noninvasive diagnostic tools for AIH.
Topics: Cohort Studies; Hepatitis, Autoimmune; Humans; Microbiota; Saliva; Veillonella
PubMed: 34094998
DOI: 10.3389/fcimb.2021.656674 -
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