Relationship of the lung microbiome with PD-L1 expression and immunotherapy response in lung cancer

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.

Relationship of The Lung Microbiome With PD-L1 Expression And Immunotherapy Response in Lung Cancer

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. Thus, these two genera may be considered targets for lung cancer immunotherapy.

Profiling of Oral Microbiota and Cytokines in COVID-19 Patients

The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been recently demonstrated in the sputum or saliva, suggesting how the shedding of viral RNA outlasts the end of symptoms. Recent data from transcriptome analysis show that the oral cavity mucosa harbors high levels of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2), highlighting its role as a double-edged sword for SARS-CoV-2 body entrance or interpersonal transmission. Here, we studied the oral microbiota structure and inflammatory profile of 26 naive severe coronavirus disease 2019 (COVID-19) patients and 15 controls by 16S rRNA V2 automated targeted sequencing and magnetic bead-based multiplex immunoassays, respectively. A significant diminution in species richness was observed in COVID-19 patients, along with a marked difference in beta-diversity. Species such as Prevotella salivae and Veillonella infantium were distinctive for COVID-19 patients, while Neisseria perflava and Rothia mucilaginosa were predominant in controls. Interestingly, these two groups of oral species oppositely clustered within the bacterial network, defining two distinct Species Interacting Groups (SIGs). COVID-19-related pro-inflammatory cytokines were found in both oral and serum samples, along with a specific bacterial consortium able to counteract them. We introduced a new parameter, named CytoCOV, able to predict COVID-19 susceptibility for an unknown subject at 71% of power with an Area Under Curve (AUC) equal to 0.995. This pilot study evidenced a distinctive oral microbiota composition in COVID-19 subjects, with a definite structural network in relation to secreted cytokines. Our results would be usable in clinics against COVID-19, using bacterial consortia as biomarkers or to reduce local inflammation.

Profiling of oral microbiota and cytokines in COVID-19 patients

ABSTRACTSARS-CoV-2 presence has been recently demonstrated in the sputum or saliva, suggesting how the shedding of viral RNA outlasts the end of symptoms. Recent data from transcriptome analysis show that oral cavity mucosa harbors high levels of ACE2 and TMPRSS2, highlighting its role as a double-edged sword for SARS-CoV-2 body entrance or interpersonal transmission. In the present study, for the first time, we demonstrate the oral microbiota structure and inflammatory profile of COVID-19 patients. Hospitalized COVID-19 patients and matched healthy controls underwent naso/oral-pharyngeal and oral swabs. Microbiota structure was analyzed by 16S rRNA V2 automated targeted sequencing, while oral and sera concentrations of 27 cytokines were assessed using magnetic bead-based multiplex immunoassays. A significant diminution in species richness was observed in COVID-19 patients, along with a marked difference in beta-diversity. Species such as Prevotella salivae and Veillonella infantium were distinctive for COVID-19 patients, while Neisseria perflava and Granulicatella elegans were predominant in controls. Interestingly, these two groups of oral species oppositely clustered within the bacterial network, defining two distinct Species Interacting Group (SIGs). Pro-inflammatory cytokines were distinctive for COVID-19 in both oral and serum samples, and we found a specific bacterial consortium able to counteract them, following a novel index called C4 firstly proposed here. We even introduced a new parameter, named CytoCOV, able to predict COVID-19 susceptibility for an unknown subject at 71% of power with an AUC equal to 0.995. This pilot study evidenced a distinctive oral microbiota composition in COVID-19 subjects, with a definite structural network in relation to secreted cytokines. Our results would pave the way for a theranostic approach in fighting COVID-19, trying to enlighten the intimate relationship among microbiota and SARS-CoV-2 infection.

Emergence of ceftriaxone-resistant Neisseria gonorrhoeae strains harbouring a novel mosaic penA gene in China

Objectives The continuous emergence of ceftriaxone-resistant Neisseria gonorrhoeae strains threatens the effectiveness of current treatment regimens for gonorrhoea. The objective of the present study was to characterize three ceftriaxone-resistant N. gonorrhoeae strains with a novel mosaic penA allele isolated in China. Methods Three ceftriaxone-resistant Neisseria gonorrhoeae strains (GC150, GC161 and GC208) isolated in 2017 were characterized by N. gonorrhoeae multiantigen sequence typing (NG-MAST), MLST and N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR). Recombination analyses were performed using the SimPlot software. Results Three strains had the same antibiotic resistance profiles, with resistance to ceftriaxone (MIC 0.5 mg/L), ciprofloxacin (MIC 8.0 mg/L), penicillin (MIC 2.0 mg/L) and tetracycline (MIC 2.0–8.0 mg/L). STs were assigned as MLST7360, NG-MAST14292 and NG-STAR1611/NG-STAR1612. The penA gene of these three strains differed from previous ceftriaxone-resistant gonococcal strains and harboured a novel mosaic allele (penA-121.001). Like N. gonorrhoeae FC428, a widely disseminated ceftriaxone-resistant strain that was initially described in Japan in 2015, all strains also possessed substitutions A311V and T483S in PBP2, which are associated with resistance to ceftriaxone. Potential recombination events were detected in penA between N. gonorrhoeae strain FC428 and commensal Neisseria species. Our results provide further evidence that the commensal Neisseria species (Neisseria cinerea and Neisseria perflava) can serve as a reservoir of ceftriaxone resistance-mediating penA sequences in clinical gonococcal strains. Conclusions The emergence of such strains may be the result of the interspecies recombination of penA genes between N. gonorrhoeae strain FC428 and commensal Neisseria species.

Is ACOS an independent nosology? Clinical signs and diagnosis of ACOS

The aim of this study was to analyze inflammation features and possible causes of asthma-COPD overlap syndrome (ACOS). Methods. Clinical examination was performed for all patients included in the study. Blood levels of alpha-1-antitripsin (AAT), immunoglobulin (Ig) G and E antibodies against four bacterial antigens (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria perflava, and Staphylococcus aureus), and lung function were measured in all the patients. Results. The study involved 175 patients including 78 patients with bronchial asthma, 39 patients with ACOS, 38 patients with COPD, and 20 healthy individuals. AAT blood level was reversely related to lung function and to increased IgG-antibody levels against bacterial antigens. Conclusion. Due to this fact, the authors suppose that the ACOS should be considered as an independent nosology distinct from asthma and COPD, and related to microbial inflammation and AAT level.

About the role of bacteria in patients with bronchial asthma, chronic obstructive pulmonary disease and ACOS

The article deals with bacterial lung microbiota in patients with bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD), bacterial inflammation of the bronchopulmonary system which can be manifested by sensitization and allergy. Also they can be a trigger with the development of bacterial inflammation. Bacteria can colonize the lungs without severe clinical, laboratory and instrumental changes. High levels of IgG to Str. pneumoniae, Neisseria perflava, Haemophilus influenza in ACOS patients can be evidence of their etiological significance. Taking into account the etiological significance of microbiota, methods of treatment of patients with COPD and BA with the use of antibiotics, vaccines and probiotics have been developed.

THE FUNCTIONAL STATUS OF NEUTROPHILS IN PATIENTS WITH BRONCHIAL ASTHMA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, BRONCHIAL ASTHMA IN COMBINATION WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND COMMUNITY-ACOUIRED PNEUMONIA

217 people were examined including BA patients (n=78), patients with COPD (n=38), patients with combined asthma and COPD (n=39), and community-acquired pneumonia patients (n=17). The control group represented patients with essential hypertension and coronary heart disease (n=25) and 20 healthy persons. NE, AAT, phagocytic activity of neutrophils (FGC), oxygen blast, respiratory function and FeNO, serum IgE and IgG antibodies to Strept. pneumoniae, Neisseria perflava, Haemofil. influenzae and Staph. aigai were determined in all patients. The indicators of the functional state of neutrophils reflected the degree and severity of bronchopulmonary inflammation. Patients with bronchial asthma in combination with COPD had bacterial inflammation, manifested by bronchial obstruction with increasing level of AAT. These features were absent in patients with BA and COPD.

Infectious and noninfectious sensibilization of patients with bronchial asthma and chronic obstructive pulmonary disease

The study included 169 patients, particulary 33 healthy people, 69 patients with asthma, 24 patients with asthma combined with chronic obstructive pulmonary disease, 35 patients with chronic obstructive pulmonary disease and 8 patients with community-acquired pneumonia. IgE was determined to mite allergens, house dust, combined pollen meadow grasses, trees and weeds. IgE and IgG were determined to allergens of Strept. pneumonia, Haemofil. influenzae, Neisseria perflava, Staph. aureus. Presence, multiplicity, severity and combination of sensibilization were detected by the presence of specific IgE to infectious and atopic allergens. We revealed sensibilization of all studied groups, including healthy people and patients with chronic obstructive pulmonary disease and community-acquired pneumonia without clinical signs of allergies. There is a statistically significant direct correlation between IgE and IgG reaction to Strept. рneumonia and Haemofil. influenzae of healthy people and patients. There is no correlation between the IgE and IgG reaction of healthy people and patients to Neisseria perflava and Staph. aureus.

Emergence and Spread of Neisseria gonorrhoeae Clinical Isolates Harboring Mosaic-Like Structure of Penicillin-Binding Protein 2 in Central Japan

ABSTRACT Of 150 clinical isolates of Neisseria gonorrhoeae recovered in 2001, we examined 55 clinical isolates of N. gonorrhoeae for which cefixime MICs were ≥0.125 μg/ml and randomly selected 15 isolates for which cefixime MICs were ≤0.06 μg/ml for analysis of alterations in the penicillin-binding protein 2 (PBP 2) gene. We found insertion of an extra codon (Asp-345a) in the transpeptidase domain of PBP 2, and this insertion occurred alone or in conjunction with other amino acid substitutions. We also found a mosaic PBP 2 that was composed of fragments of the PBP 2 proteins from Neisseria cinera and Neisseria perflava. This mosaic PBP 2 was significantly associated with decreased susceptibilities to penicillin and cephalosporins, especially oral cephalosporins. For most of the isolates with a mosaic PBP 2, the cefixime MICs were ≥0.5 μg/ml and the cefdinir MICs were ≥1 μg/ml. Analysis of chromosomal DNA restriction patterns by pulsed-field gel electrophoresis revealed that most isolates with the mosaic PBP 2 were genetically similar. The recombination events that generated the mosaic PBP 2 would likely have contributed to the decreased sensitivities to cephalosporins. Isolates with the mosaic PBP 2 appear to threaten the efficacy of the currently recommended regimen with cefixime. The emergence of such strains may be the result of the in vivo generation of clones in which interspecies recombination occurred between the penA genes of N. gonorrhoeae and commensal Neisseria species.