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Nature Medicine May 2024Despite substantial progress in cancer microbiome research, recognized confounders and advances in absolute microbiome quantification remain underused; this raises...
Despite substantial progress in cancer microbiome research, recognized confounders and advances in absolute microbiome quantification remain underused; this raises concerns regarding potential spurious associations. Here we study the fecal microbiota of 589 patients at different colorectal cancer (CRC) stages and compare observations with up to 15 published studies (4,439 patients and controls total). Using quantitative microbiome profiling based on 16S ribosomal RNA amplicon sequencing, combined with rigorous confounder control, we identified transit time, fecal calprotectin (intestinal inflammation) and body mass index as primary microbial covariates, superseding variance explained by CRC diagnostic groups. Well-established microbiome CRC targets, such as Fusobacterium nucleatum, did not significantly associate with CRC diagnostic groups (healthy, adenoma and carcinoma) when controlling for these covariates. In contrast, the associations of Anaerococcus vaginalis, Dialister pneumosintes, Parvimonas micra, Peptostreptococcus anaerobius, Porphyromonas asaccharolytica and Prevotella intermedia remained robust, highlighting their future target potential. Finally, control individuals (age 22-80 years, mean 57.7 years, standard deviation 11.3) meeting criteria for colonoscopy (for example, through a positive fecal immunochemical test) but without colonic lesions are enriched for the dysbiotic Bacteroides2 enterotype, emphasizing uncertainties in defining healthy controls in cancer microbiome research. Together, these results indicate the importance of quantitative microbiome profiling and covariate control for biomarker identification in CRC microbiome studies.
Topics: Humans; Colorectal Neoplasms; Middle Aged; Feces; Female; Aged; Male; RNA, Ribosomal, 16S; Adult; Gastrointestinal Microbiome; Aged, 80 and over; Young Adult; Microbiota; Leukocyte L1 Antigen Complex
PubMed: 38689063
DOI: 10.1038/s41591-024-02963-2 -
Clinical Oral Investigations Mar 2016The objective of this study was to compare the periodontopathogen prevalence and tetracycline resistance genes in Dominican patients with different periodontal...
OBJECTIVE
The objective of this study was to compare the periodontopathogen prevalence and tetracycline resistance genes in Dominican patients with different periodontal conditions.
METHODS
Seventy-seven samples were collected from healthy, gingivitis, chronic (CP) and aggressive (AgP) periodontitis patients. Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Prevotella intermedia, Parvimonas micra, Eikenella corrodens and Dialister pneumosintes and 11 resistance genes were studied by PCR. P. gingivalis fimA genotype was determined.
RESULTS
In healthy patients, P. micra and P. intermedia were the most and least frequently detected, respectively. T. forsythia and E. corrodens appeared in 100% of gingivitis patients. Red complex, D. pneumosintes and E. corrodens were significantly more prevalent in CP compared to healthy patients. F. nucleatum and T. denticola were detected more frequently in AgP. A. actinomycetemcomitans was the most rarely observed in all groups. The fimA II genotype was the most prevalent in periodontitis patients. Seven tetracycline-resistant genes were detected. tet(Q), tet(32) and tet(W) showed the greatest prevalence. tet(32) was significantly more prevalent in CP than in healthy patients.
CONCLUSIONS
Red complex bacteria and D. pneumosintes were significantly the most prevalent species among periodontitis patients. T. forsythia was the most frequently detected in this population. To our knowledge, this is the first study describing the tet(32) gene in subgingival biofilm from healthy and periodontally diseased subjects.
CLINICAL RELEVANCE
This study contributes to the knowledge on the subgingival microbiota and its resistance genes of a scarcely studied world region. Knowing the prevalence of resistance genes could impact on their clinical prescription and could raise awareness to the appropriate use of antibiotics.
Topics: Adult; Aged; Bacterial Infections; Biofilms; Case-Control Studies; Dominican Republic; Female; Genotype; Humans; Male; Microbiota; Middle Aged; Periodontitis; Polymerase Chain Reaction; Prevalence; Tetracycline Resistance
PubMed: 26121972
DOI: 10.1007/s00784-015-1516-2 -
Journal of Oral Microbiology 2014We recently reported that large amounts of oral bacterial DNA can be found in thrombus aspirates of myocardial infarction patients. Some case reports describe bacterial...
BACKGROUND
We recently reported that large amounts of oral bacterial DNA can be found in thrombus aspirates of myocardial infarction patients. Some case reports describe bacterial findings in pericardial fluid, mostly done with conventional culturing and a few with PCR; in purulent pericarditis, nevertheless, bacterial PCR has not been used as a diagnostic method before.
OBJECTIVE
To find out whether bacterial DNA can be measured in the pericardial fluid and if it correlates with pathologic-anatomic findings linked to cardiovascular diseases.
METHODS
Twenty-two pericardial aspirates were collected aseptically prior to forensic autopsy at Tampere University Hospital during 2009-2010. Of the autopsies, 10 (45.5%) were free of coronary artery disease (CAD), 7 (31.8%) had mild and 5 (22.7%) had severe CAD. Bacterial DNA amounts were determined using real-time quantitative PCR with specific primers and probes for all bacterial strains associated with endodontic disease (Streptococcus mitis group, Streptococcus anginosus group, Staphylococcus aureus/Staphylococcus epidermidis, Prevotella intermedia, Parvimonas micra) and periodontal disease (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Fusobacterium nucleatus, and Dialister pneumosintes).
RESULTS
Of 22 cases, 14 (63.6%) were positive for endodontic and 8 (36.4%) for periodontal-disease-associated bacteria. Only one case was positive for bacterial culturing. There was a statistically significant association between the relative amount of bacterial DNA in the pericardial fluid and the severity of CAD (p=0.035).
CONCLUSIONS
Oral bacterial DNA was detectable in pericardial fluid and an association between the severity of CAD and the total amount of bacterial DNA in pericardial fluid was found, suggesting that this kind of measurement might be useful for clinical purposes.
PubMed: 25412607
DOI: 10.3402/jom.v6.25835 -
World Journal of Gastrointestinal... Sep 2019Impaired anastomotic healing is one of the major complications resulting from radical resection in colorectal cancer (CRC). Accumulating evidence suggests that...
BACKGROUND
Impaired anastomotic healing is one of the major complications resulting from radical resection in colorectal cancer (CRC). Accumulating evidence suggests that intestinal microbiota is correlated with anastomotic healing.
AIM
To explore the microbiota structural shift in margin-surrounding mucosa and evaluate the predictive ability of selected bacterial taxa for impaired anastomotic healing.
METHODS
Margin-surrounding mucosa samples derived from 37 patients were collected to characterize the microbial community structure by 16s rRNA gene sequencing. The patients were divided into two groups according to the healing status of anastomoses: well-healing group ( = 30) and impaired-healing group ( = 7). Statistic differences in bacteria taxa were compared by Wilcoxon test and chi-squared test. The predictive ability of the selected bacterial taxa for the healing status of anastomoses was evaluated by the area under the receiver operator characteristic curve.
RESULTS
Community structure shifts were observed in the impaired-healing group and well-healing group. Six bacterial species were found to be significantly correlated with anastomotic healing, and among these species, , , and were considered as the predictive factors. Taking the known risk factor age into consideration, , , and improved predictive ability for the healing status of anastomoses.
CONCLUSION
These data show that , , and could be considered as supplementary factors in the prediction of anastomosis healing status in patients after CRC radical resection.
PubMed: 31558976
DOI: 10.4251/wjgo.v11.i9.717 -
Journal of Dental Research Nov 2010The subgingival microbiome is largely uncultivated, and therefore, cultivation-based and targeted molecular approaches have limited value in examining the effect of... (Comparative Study)
Comparative Study
The subgingival microbiome is largely uncultivated, and therefore, cultivation-based and targeted molecular approaches have limited value in examining the effect of smoking on this community. We tested the hypothesis that the subgingival biofilm is compositionally different in current and never-smokers by using an open-ended molecular approach for bacterial identification. Subgingival plaque from deep sites of current and never-smokers matched for disease was analyzed by 16S sequencing. Smokers demonstrated greater abundance of Parvimonas, Fusobacterium, Campylobacter, Bacteroides, and Treponema and lower levels of Veillonella, Neisseria, and Streptococcus. Several uncultivated Peptostreptococci, Parvimonas micra, Campylobacter gracilis, Treponema socranskii, Dialister pneumosintes, and Tannerella forsythia were elevated in this group, while Veillonella sp. oral clone B2, Neisseria sp. oral clone 2.24, Streptococcus sanguinis, and Capnocytophaga sp. clone AH015 were at lower levels. The microbial profile of smoking-associated periodontitis is distinct from that of non-smokers, with significant differences in the prevalence and abundance of disease-associated and health-compatible organisms.
Topics: Alveolar Bone Loss; Bacteria; Bacteroides; Biofilms; Campylobacter; Capnocytophaga; Case-Control Studies; Chronic Periodontitis; Dental Plaque; Female; Fusobacterium; Gingiva; Gram-Negative Anaerobic Straight, Curved, and Helical Rods; Humans; Male; Middle Aged; Neisseria; Peptostreptococcus; Periodontal Attachment Loss; Periodontal Pocket; Smoking; Streptococcus; Treponema; Veillonella
PubMed: 20739702
DOI: 10.1177/0022034510377203 -
World Journal of Gastroenterology Nov 2021Immunotherapy has revolutionized the clinical outcomes of intractable cancer patients. Little is known about the intestinal nonpathogenic bacterial composition of...
BACKGROUND
Immunotherapy has revolutionized the clinical outcomes of intractable cancer patients. Little is known about the intestinal nonpathogenic bacterial composition of hepatocellular carcinoma (HCC) patients treated by immunotherapy.
AIM
To determine whether there is a correlation between gut bacterial composition and prognosis in HCC patients.
METHODS
From September 2019 to March 2020, we prospectively collected fecal samples and examined the gut microbiome of 8 advanced HCC patients treated with nivolumab as a second- or third-line systemic treatment. Fecal samples were collected before the start of immunotherapy. Fecal samples of patients with progression during treatment were collected at the time of progression, and fecal samples of patients who showed good response to nivolumab were collected after 5-7 mo as follow-up. Metagenomic data from 16S ribosomal RNA sequencing were analyzed using CLC Genomics Workbench. Microbiome data were analyzed according to therapeutic response.
RESULTS
All 8 patients were male, of which 6 had underlying chronic hepatitis B. A higher Shannon index was found in the responders than in the non-responders after nivolumab therapy ( = 0.036). The unweighted beta diversity analysis also showed that the overall bacterial community structure and phylogenetic diversity were clearly distinguished according to therapeutic response. There was no significant difference in the diversity or composition of the patient gut microbiome according to the immunotherapy used. Several taxa specific to therapeutic response were designated as follows: sp., and for the non-responders; sp. and for the responders. Of note, a skewed ratio and a low ratio can serve as predictive markers of non-response, whereas the presence of species predicts a good response.
CONCLUSION
The current presumptive study suggests a potential role for the gut microbiome as a prognostic marker for the response to nivolumab in treatment of HCC patients.
Topics: Carcinoma, Hepatocellular; Feces; Gastrointestinal Microbiome; Humans; Liver Neoplasms; Male; Nivolumab; Phylogeny; RNA, Ribosomal, 16S
PubMed: 34876793
DOI: 10.3748/wjg.v27.i42.7340 -
Oral Diseases Sep 2012To compare the microbiota of endodontic infections in necrotic pulp from HIV-negative and HIV-positive subjects. (Comparative Study)
Comparative Study
OBJECTIVE
To compare the microbiota of endodontic infections in necrotic pulp from HIV-negative and HIV-positive subjects.
MATERIALS AND METHODS
Root canal samples from necrotic pulp were collected from 40 HIV- and 20 HIV+ subjects. Pulps were amplified using multiple displacement amplification (MDA). Then, checkerboard DNA-DNA hybridization was employed to assess the levels of 107 microbial taxa. The percentage of DNA probe count and the percentage of teeth colonized by each test species were investigated. Significant differences between groups regarding proportions of taxa and prevalence of the test species were sought using the Mann-Whitney test and the Chi-square analysis, respectively.
RESULTS
The most prevalent taxa detected were Dialister pneumosintes, Stenotrophomonas maltophilia, Streptococcus sobrinus, Corynebacterium diphteriae, and Helicobacter pylori among HIV- subjects and D. pneumosintes, Prevotella tannerae, Porphyromonas gingivalis, Parvimonas micra, Prevotella nigrescens, and Corynebacterium diphtheriae among HIV+ individuals. D. pneumosintes, C. diphtheria, and C. albicans were the most abundant species in the HIV- group, whereas the predominant taxa in HIV+ samples were P. tannerae, D. pneumosintes and Olsenella uli. P. tannerae, O. uli, Veilonella dispar, Bacteroides fragilis, and Actinomyces meyeri were significantly more abundant in HIV+ samples.
CONCLUSIONS
There were significant differences in the prevalence and proportions of specific microbial taxa between HIV- and HIV+ individuals. The root canal microbiota may represent a reservoir of important oral and medical pathogens, mainly in HIV+ individuals.
Topics: Actinomyces; Adolescent; Adult; Bacteria; Bacteroides fragilis; Candida albicans; Child; Corynebacterium diphtheriae; DNA Probes; Dental Pulp Cavity; Dental Pulp Necrosis; Female; Gram-Negative Anaerobic Straight, Curved, and Helical Rods; HIV Seronegativity; HIV Seropositivity; Helicobacter pylori; Humans; Male; Middle Aged; Nucleic Acid Amplification Techniques; Nucleic Acid Hybridization; Peptostreptococcus; Porphyromonas gingivalis; Prevotella; Prevotella nigrescens; Stenotrophomonas maltophilia; Streptococcus sobrinus; Veillonella; Young Adult
PubMed: 22335194
DOI: 10.1111/j.1601-0825.2012.01908.x -
Journal of Clinical Microbiology Jul 2010It has been demonstrated that smoking cessation alters the subgingival microbial profile; however, the response of individual bacteria within this ecosystem has not been...
It has been demonstrated that smoking cessation alters the subgingival microbial profile; however, the response of individual bacteria within this ecosystem has not been well studied. The aim of this investigation, therefore, was to longitudinally examine the effect of smoking cessation on the prevalence and levels of selected subgingival bacteria using molecular approaches for bacterial identification and enumeration. Subgingival plaque was collected from 22 smokers at the baseline and 12 months following periodontal nonsurgical management and smoking cessation counseling. The prevalence and abundance of selected organisms were examined using nested PCR and multiplexed bead-based flow cytometry. Eleven subjects successfully quit smoking over 12 months (quitters), while 11 continued to smoke throughout (smokers). Smoking cessation led to a decrease in the prevalence of Porphyromonas endodontalis and Dialister pneumosintes at 12 months and in the levels of Parvimonas micra, Filifactor alocis, and Treponema denticola. Smoking cessation also led to an increase in the levels of Veillonella parvula. Following nonsurgical periodontal therapy and smoking cessation, the subgingival microbiome is recolonized by a greater number of health-associated species and there are a significantly lower prevalence and abundance of putative periodontal pathogens. The results indicate a critical role for smoking cessation counseling in periodontal therapy for smokers in order to effectively alter the subgingival microbiome.
Topics: Analysis of Variance; Bacteria; Cross-Sectional Studies; DNA, Bacterial; Gingiva; Humans; Polymerase Chain Reaction; Smoking; Smoking Cessation; Statistics, Nonparametric
PubMed: 20410352
DOI: 10.1128/JCM.01821-09 -
NPJ Biofilms and Microbiomes 2017We have previously reported that oral biofilms in clinically healthy smokers are pathogen-rich, and that this enrichment occurs within 24 h of biofilm formation. The...
We have previously reported that oral biofilms in clinically healthy smokers are pathogen-rich, and that this enrichment occurs within 24 h of biofilm formation. The present investigation aimed to identify a mechanism by which smoking creates this altered community structure. By combining in vitro microbial-mucosal interface models of commensal (consisting of and and pathogen-rich (comprising and , and communities with metatranscriptomics, targeted proteomics and fluorescent microscopy, we demonstrate that smoke exposure significantly downregulates essential metabolic functions within commensal biofilms, while significantly increasing expression of virulence genes, notably lipopolysaccharide (LPS), flagella and capsule synthesis. By contrast, in pathogen-rich biofilms several metabolic pathways were over-expressed in response to smoke exposure. Under smoke-rich conditions, epithelial cells mounted an early and amplified pro-inflammatory and oxidative stress response to these virulence-enhanced commensal biofilms, and a muted early response to pathogen-rich biofilms. Commensal biofilms also demonstrated early and widespread cell death. Similar results were observed when smoke-free epithelial cells were challenged with smoke-conditioned biofilms, but not vice versa. In conclusion, our data suggest that smoke-induced transcriptional shifts in commensal biofilms triggers a florid pro-inflammatory response, leading to early commensal death, which may preclude niche saturation by these beneficial organisms. The cytokine-rich, pro-oxidant, anaerobic environment sustains inflammophilic bacteria, and, in the absence of commensal antagonism, may promote the creation of pathogen-rich biofilms in smokers.
PubMed: 29081982
DOI: 10.1038/s41522-017-0033-2 -
BMJ Case Reports Mar 2022A man in his twenties with a history of recurrent sinusitis was urgently referred to the emergency department (ED) by an out-of-hours general practitioner following a...
A man in his twenties with a history of recurrent sinusitis was urgently referred to the emergency department (ED) by an out-of-hours general practitioner following a 2-day history of increasing right eye pain, redness and swelling after a week of coryzal symptoms. He denied visual impairment and any history of recent dental pain or procedures. Initial assessment in ED noted fever, tachycardia and hypotension. Video consultation with ophthalmologist in the ED identified proptosis, periorbital erythema and chemosis with full eye movement solely affecting the right eye. Visual acuity of 6/6 was confirmed in both eyes. After review by the ear, nose and throat (ENT) team, a diagnosis of sinogenic right orbital cellulitis was made, empirical antibiotics started and care transferred to the ENT team for immediate surgical intervention. 48 hours postoperatively, the patient acutely deteriorated, developing ophthalmoplegia and visual acuity of 6/95 in the right eye. Repeat imaging demonstrated a deteriorating picture and urgent surgery was organised at a neighbouring hospital's specialist ENT unit combined with a change to his antibiotics. On day 4, 1 day following transfer, an anaerobic bacterium, was isolated from blood cultures collected on admission. The patient improved clinically following the second surgery and targeted antimicrobial therapy, eventually being discharged 10 days after initial presentation. In addition to , the Anaerobic Reference Unit (Cardiff) identified two further anaerobic bacteria, and This paper presents the first documented case of polymicrobial anaerobic orbital cellulitis secondary to acute bacterial sinusitis. Moreover, this case underpins the importance of broad empirical antibiotics coupled with surgical source control to effectively manage a rare but sight-threatening and life-threatening disease.
Topics: Anaerobiosis; Anti-Bacterial Agents; Base Composition; Humans; Male; Orbital Cellulitis; Phylogeny; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Tomography, X-Ray Computed
PubMed: 35351758
DOI: 10.1136/bcr-2021-248473