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Relationship of the lung microbiome with PD-L1 expression and immunotherapy response in lung cancer.Respiratory Research Dec 2021Lung cancer is the primary cause of cancer-related deaths worldwide. The human lung serves as a niche to a unique and dynamic bacterial community that is related to the...
BACKGROUND
Lung cancer is the primary cause of cancer-related deaths worldwide. The human lung serves as a niche to a unique and dynamic bacterial community that is related to the development of multiple diseases. Here, we investigated the differences in the lung microbiomes of patients with lung cancer.
METHODS
16S rRNA sequencing was performed to evaluate the respiratory tract microbiome present in the bronchoalveolar lavage fluid. Patients were stratified based on programmed death-ligand 1 (PD-L1) expression levels and immunotherapy responses.
RESULTS
In total, 84 patients were prospectively analyzed, of which 59 showed low (< 10%), and 25 showed high (≥ 10%) PD-L1 expression levels. The alpha and beta diversities did not significantly differ between the two groups. Veillonella dispar was dominant in the high-PD-L1 group; the population of Neisseria was significantly higher in the low-PD-L1 group than in the high-PD-L1 group. In the immunotherapy responder group, V. dispar was dominant, while Haemophilus influenzae and Neisseria perflava were dominant in the non-responder group.
CONCLUSION
The abundances of Neisseria and V. dispar differed significantly in relation to PD-L1 expression levels and immunotherapy responses.
Topics: Aged; Antineoplastic Agents, Immunological; B7-H1 Antigen; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Female; Gene Expression Regulation, Neoplastic; Humans; Immunotherapy; Lung; Lung Neoplasms; Male; Microbiota; Middle Aged; Prospective Studies
PubMed: 34963470
DOI: 10.1186/s12931-021-01919-1 -
Lupus Science & Medicine Oct 2021The risk factors associated with urinary tract infections (UTIs) in patients with SLE remain uncertain. We evaluated the vaginal microbiota pattern and its potential...
OBJECTIVE
The risk factors associated with urinary tract infections (UTIs) in patients with SLE remain uncertain. We evaluated the vaginal microbiota pattern and its potential UTI-associated risk factors.
METHODS
A pilot cross-sectional study of patients with SLE was conducted at Ramathibodi Hospital, Bangkok, Thailand, during 2019-2020. Patients' demographic data and relevant information were collected. Vaginal microbiota was assessed in all patients and in 10 healthy volunteers.
RESULTS
Fifty-two patients were enrolled (mean age: 46.1 years). All patients had SLE that was in low disease activity. As per the Simpson_e index, the within-group alpha diversity of the vaginal microbiota was low in the SLE with UTI and SLE receiving trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis groups. Multivariate logistic regression analysis revealed that TMP-SMX prophylaxis (adjusted OR (AOR), 30.96; 95% CI 3.63 to 264.11; p=0.002), elevated C3 levels (AOR, 35.33; 95% CI 1.33 to 936.67; p=0.033) and presence of in the vaginal microbiota (AOR, 6.68; 95% CI 1.27 to 35.07; p=0.025) were associated with UTI.
CONCLUSIONS
The vaginal microbiota diversity differed between patients with lupus with and without UTI, and unnecessary administration of TMP-SMX prophylaxis may affect the alpha diversity of the vaginal microbiota.
Topics: Cross-Sectional Studies; Female; Humans; Lupus Erythematosus, Systemic; Microbiota; Middle Aged; Thailand; Urinary Tract Infections; Veillonella
PubMed: 34706864
DOI: 10.1136/lupus-2021-000551 -
Cureus Sep 2021We present the case of a 50-year-old man presenting with fever, back pain, persistent bacteremia with , echocardiographic evidence of a tricuspid valve vegetation...
We present the case of a 50-year-old man presenting with fever, back pain, persistent bacteremia with , echocardiographic evidence of a tricuspid valve vegetation increasing in size, and magnetic resonance imaging suggesting new vertebral osteomyelitis. He was successfully treated with intravenous ceftriaxone for six weeks. Deep-seated infections secondary to species are rare, but cases of endocarditis, osteomyelitis, and meningitis have been reported in the literature. Given species are normal human commensals present in the oropharyngeal flora, we suspect our patient developed native tricuspid valve endocarditis and vertebral osteomyelitis as a complication of either poor dentition or contaminated injection drug use paraphernalia and subsequent hematogenous seeding.
PubMed: 34667667
DOI: 10.7759/cureus.17989 -
Frontiers in Microbiology 2021The self-produced matrix of biofilms, consisting of extracellular polymeric substances, plays an important role in biofilm adhesion to surfaces and the structural...
The self-produced matrix of biofilms, consisting of extracellular polymeric substances, plays an important role in biofilm adhesion to surfaces and the structural integrity of biofilms. In dentistry, biofilms cause multiple diseases such as caries, periodontitis, and pulpitis. Disruption of these biofilms adhering to dental hard tissues may pose a major challenge since biofilms show higher tolerance to antimicrobials and antibiotics than planktonic cells. In this study, the effect of low concentrations of chlorhexidine (CHX) on enzyme-treated multispecies oral biofilm was investigated in an model. Six-species biofilms were enzymatically treated by anaerobic growth in a medium containing DNase I and proteinase K. Biofilms were exposed to a low concentration of CHX at defined time points. After 64h, biofilms were either harvested and quantified by cultural analyses or stained for confocal laser scanning microscopy (CLSM) analyses using either Live/Dead kit or different fluorescent dyes. A mixture of YoPro1 and SYTOX Green, Fluorescent Brightener 28 (Calcofluor), and SYPRO Ruby Protein Gel Stain was used to stain total DNA, exopolysaccharides, and extracellular proteins, respectively. Extracellular DNA (eDNA) was visualized an indirect immunofluorescence assay (Mouse anti-DNA IgG, Goat anti-Mouse IgG, Streptavidin-Cy3). Overall, the total colony-forming units significantly decreased after combined treatment with a low concentration of CHX and enzymes compared to the group treated with CHX alone (<0.001). These findings also apply to five species individually ( and ) occurring in the biofilms, with being the only exception. Furthermore, CLSM images showed less dense biofilms and a reduction in cell numbers after combined treatment compared to the group without enzymes. The combination of enzymes capable of disturbing the matrix integrity with antimicrobial agents thus appears to be a promising approach for biofilm disruption and killing.
PubMed: 34650542
DOI: 10.3389/fmicb.2021.741863 -
BMC Oral Health Jun 2021Supragingival plaque and saliva are commonly used for microbiome analysis. Many epidemiological studies have identified deciduous teeth caries as a risk factor for...
BACKGROUND
Supragingival plaque and saliva are commonly used for microbiome analysis. Many epidemiological studies have identified deciduous teeth caries as a risk factor for caries development in first permanent molar (FPM); nevertheless, to the best of our knowledge, there are no reports on the effects of deciduous teeth caries on the microbiome of healthy FPM. Additionally, it remains unclear whether saliva can be used instead of supragingival plaque for caries microbial studies. Therefore, we aimed to elucidate this issue, and to characterize and compare the oral microbiome of healthy FPMs in children with different caries statuses and that from children with and without caries in a similar microhabitat, by PacBio sequencing. Currently, few studies have investigated the oral microbiome of children using this technique.
METHODS
Thirty children (aged 7-9 years) with mixed dentition were enrolled; 15 had dental caries, and 15 did not. Supragingival plaques of deciduous molars and maxillary FPMs, and non-stimulating saliva samples were collected. DNA was extracted and the v1-v9 regions of 16S rRNA were amplified. Subsequently, PacBio sequencing and bioinformatic analyses were performed for microbiome identification.
RESULTS
The microbial alpha diversity of the saliva samples was lower than that of the supragingival plaque (p < 0.05); however, no differences were detected between deciduous teeth and FPMs (p > 0.05). In addition, the alpha and beta diversity of children with and without caries was also similar (p > 0.05). Nonmetric multidimensional scaling and Adonis analyses indicated that the microbial structure of salivary and supragingival plaque samples differ (p < 0.05). Further analysis of deciduous teeth plaque showed that Streptococcus mutans, Propionibacterium acidifaciens, and Veillonella dispar were more abundant in children with caries than in those without (p < 0.05); while in FPMs plaque, Selenomonas noxia was more abundant in healthy children (p < 0.05). No differences in microorganisms abundance were found in the saliva subgroups (p > 0.05).
CONCLUSION
We have determined that supragingival plaque was the best candidate for studying carious microbiome. Furthermore, S. mutans, V. dispar, and P. acidifaciens were highly associated with deciduous teeth caries. S. noxia may be associated with the abiding health of FPM; however, this requires additional studies.
Topics: Child; Cross-Sectional Studies; Dental Caries; Dental Caries Susceptibility; Dentition, Mixed; Humans; Microbiota; Propionibacterium; RNA, Ribosomal, 16S; Saliva; Selenomonas; Veillonella
PubMed: 34172026
DOI: 10.1186/s12903-021-01683-0 -
Synthetic and Systems Biotechnology Sep 2021SARS-CoV-2, the causative agent for COVID-19, infect human mainly via respiratory tract, which is heavily inhabited by local microbiota. However, the interaction between...
SARS-CoV-2, the causative agent for COVID-19, infect human mainly via respiratory tract, which is heavily inhabited by local microbiota. However, the interaction between SARS-CoV-2 and nasopharyngeal microbiota, and the association with metabolome has not been well characterized. Here, metabolomic analysis of blood, urine, and nasopharyngeal swabs from a group of COVID-19 and non-COVID-19 patients, and metagenomic analysis of pharyngeal samples were used to identify the key features of COVID-19. Results showed lactic acid, l-proline, and chlorogenic acid methyl ester (CME) were significantly reduced in the sera of COVID-19 patients compared with non-COVID-19 ones. Nasopharyngeal commensal bacteria including , and were notably depleted in the pharynges of COVID-19 patients, while , , and were relatively increased. The abundance of and were significantly positively associated with serum CME, which might be an anti-SARS-CoV-2 bacterial metabolite. This study provides important information to explore the linkage between nasopharyngeal microbiota and disease susceptibility. The findings were based on a very limited number of patients enrolled in this study; a larger size of cohort will be appreciated for further investigation.
PubMed: 34151035
DOI: 10.1016/j.synbio.2021.06.002 -
Frontiers in Microbiology 2021Information on the time when a stain was deposited at a crime scene can be valuable in forensic investigations. It can link a DNA-identified stain donor with a crime or...
Information on the time when a stain was deposited at a crime scene can be valuable in forensic investigations. It can link a DNA-identified stain donor with a crime or provide a post-mortem interval estimation in cases with cadavers. The available methods for estimating stain deposition time have limitations of different types and magnitudes. In this proof-of-principle study we investigated for the first time the use of microbial DNA for this purpose in human saliva stains. First, we identified the most abundant and frequent bacterial species in saliva using publicly available 16S rRNA gene next generation sequencing (NGS) data from 1,848 samples. Next, we assessed time-dependent changes in 15 identified species using de-novo 16S rRNA gene NGS in the saliva stains of two individuals exposed to indoor conditions for up to 1 year. We selected four bacterial species, i.e., , and showing significant time-dependent changes and developed a 4-plex qPCR assay for their targeted analysis. Then, we analyzed the saliva stains of 15 individuals exposed to indoor conditions for up to 1 month. Bacterial counts generally increased with time and explained 54.9% of the variation ( = <2.2E-16). Time since deposition explained ≥86.5% and ≥88.9% of the variation in each individual and species, respectively ( = <2.2E-16). Finally, based on sample duplicates we built and tested multiple linear regression models for predicting the stain deposition time at an individual level, resulting in an average mean absolute error (MAE) of 5 days (ranging 3.3-7.8 days). Overall, the deposition time of 181 (81.5%) stains was correctly predicted within 1 week. Prediction models were also assessed in stains exposed to similar conditions up to 1 month 7 months later, resulting in an average MAE of 8.8 days (ranging 3.9-16.9 days). Our proof-of-principle study suggests the potential of the DNA profiling of human commensal bacteria as a method of estimating saliva stains time since deposition in the forensic scenario, which may be expanded to other forensically relevant tissues. The study considers practical applications of this novel approach, but various forensic developmental validation and implementation criteria will need to be met in more dedicated studies in the future.
PubMed: 34149638
DOI: 10.3389/fmicb.2021.647933 -
Scientific Reports May 2021COVID-19 infection may predispose to secondary bacterial infection which is associated with poor clinical outcome especially among critically ill patients. We aimed to...
COVID-19 infection may predispose to secondary bacterial infection which is associated with poor clinical outcome especially among critically ill patients. We aimed to characterize the lower respiratory tract bacterial microbiome of COVID-19 critically ill patients in comparison to COVID-19-negative patients. We performed a 16S rRNA profiling on bronchoalveolar lavage (BAL) samples collected between April and May 2020 from 24 COVID-19 critically ill subjects and 24 patients with non-COVID-19 pneumonia. Lung microbiome of critically ill patients with COVID-19 was characterized by a different bacterial diversity (PERMANOVA on weighted and unweighted UniFrac Pr(> F) = 0.001) compared to COVID-19-negative patients with pneumonia. Pseudomonas alcaligenes, Clostridium hiranonis, Acinetobacter schindleri, Sphingobacterium spp., Acinetobacter spp. and Enterobacteriaceae, characterized lung microbiome of COVID-19 critically ill patients (LDA score > 2), while COVID-19-negative patients showed a higher abundance of lung commensal bacteria (Haemophilus influenzae, Veillonella dispar, Granulicatella spp., Porphyromonas spp., and Streptococcus spp.). The incidence rate (IR) of infections during COVID-19 pandemic showed a significant increase of carbapenem-resistant Acinetobacter baumannii (CR-Ab) infection. In conclusion, SARS-CoV-2 infection and antibiotic pressure may predispose critically ill patients to bacterial superinfection due to opportunistic multidrug resistant pathogens.
Topics: Aged; Bacteria; Bronchoalveolar Lavage Fluid; COVID-19; Critical Illness; Dysbiosis; Female; Humans; Lung; Male; Microbiota; Middle Aged; SARS-CoV-2
PubMed: 33980943
DOI: 10.1038/s41598-021-89516-6 -
Antibiotics (Basel, Switzerland) Apr 2021Biofilm virulence is mainly based on its bacterial cell surrounding biofilm matrix, which contains a scaffold of exopolysaccharides, carbohydrates, proteins, lipids, and...
Biofilm virulence is mainly based on its bacterial cell surrounding biofilm matrix, which contains a scaffold of exopolysaccharides, carbohydrates, proteins, lipids, and nucleic acids. Targeting these nucleid acids or proteins could enable an efficient biofilm control. Therefore, the study aimed to test the effect of deoxyribonuclease I (DNase I) and proteinase K on oral biofilms. Six-species biofilms (, , , , , and were exposed to DNase I (0.001 mg/mL, 0.002 mg/mL) or proteinase K (0.05 mg/mL, 0.1 mg/mL) for 1 h during biofilm formation. After 64 h, biofilms were harvested, quantified by culture analysis and visualized by image analysis using CLSM (confocal laser scanning microscopy). Statistical analysis was performed by ANOVA, followed by the Tukey test at a 5% significance level. The biofilm treatment with proteinase K induced a significant increase of Logs counts in and a decrease in , while biofilm thickness was reduced from 28.5 μm (control) to 9.07 μm (0.05 mg/mL) and 7.4 μm (0.1 mg/mL). Treatment with DNase I had no effect on the total bacterial growth within the biofilm. Targeting proteins of biofilms by proteinase K are promising adjunctive tool for biofilm control.
PubMed: 33917114
DOI: 10.3390/antibiotics10040400 -
BMC Oral Health Apr 2021Excessive biofilm formation on surfaces in the oral cavity is amongst the main reasons for severe infection development like periodontitis and peri-implantitis....
BACKGROUND
Excessive biofilm formation on surfaces in the oral cavity is amongst the main reasons for severe infection development like periodontitis and peri-implantitis. Mechanical biofilm removal as well as the use of adjuvant antiseptics supports the prevention of pathogenic biofilm formation. Recently, the antibacterial effect of the oral care product REPHA-OS, based on medicinal plant extracts and essential oils, has been demonstrated on oral pathogens grown on agar plates. In the present study, the effectiveness of the product on medical relevant oral biofilm development should be demonstrated for the first time.
METHODS
An established in vitro oral multispecies biofilm, composed of Streptococcus oralis, Actinomyces naeslundii, Veillonella dispar and Porphyromonas gingivalis, was used to analyze the antibacterial effect of different REPHA-OS concentrations on planktonic bacteria, biofilm formation and mature biofilms. It was quantified using metabolic activity assays and live/dead fluorescence staining combined with three-dimensional confocal laser-scanning microscopy. Additionally, effects on species distribution inside the biofilm were assessed by means of quantitative real-time PCR.
RESULTS
REPHA-OS showed statistically significant antimicrobial effects on all stages of biofilm development: a minimal inhibitory concentration of 5% could be detected for both, for planktonic bacteria and for biofilm formation. Interestingly, only a slightly higher concentration of 10% was necessary to completely kill all bacteria in mature biofilms also. In contrast, an influence on the biofilm matrix or the species distribution could not be observed. The effect could be attributed to the herbal ingredients, not to the contained ethanol.
CONCLUSION
The strong antibacterial effect of REPHA-OS on different stages of oral biofilm development strengthens its application as an alternative adjuvant in oral care therapies.
Topics: Actinomyces; Anti-Bacterial Agents; Biofilms; Veillonella
PubMed: 33794846
DOI: 10.1186/s12903-021-01504-4