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Thoracic Cancer Apr 2024The causal relationship between breast cancer (BC) and the oral microbiome remains unclear. In this case-control study, using two-sample Mendelian randomization (MR), we...
BACKGROUND
The causal relationship between breast cancer (BC) and the oral microbiome remains unclear. In this case-control study, using two-sample Mendelian randomization (MR), we thoroughly explored the relationship between the oral microbiome and BC in the East Asian population.
METHODS
Genetic summary data related to oral microbiota and BC were collected from genome-wide association studies involving participants of East Asian descent. MR estimates were generated by conducting various analyses. Sequencing data from a case-control study were used to verify the validity of these findings.
RESULTS
MR analysis revealed that 30 tongue and 37 salivary bacterial species were significantly associated with BC. Interestingly, in both tongue and salivary microbiomes, we observed the causal effect of six genera, namely, Aggregatibacter, Streptococcus, Prevotella, Haemophilus, Lachnospiraceae, Oribacterium, and Solobacterium, on BC. Our case-control study findings suggest differences in specific bacteria between patients with BC and healthy controls. Moreover, sequencing data confirmed the MR analysis results, demonstrating that compared with the healthy control group, the BC group had a higher relative abundance of Pasteurellaceae and Streptococcaceae but a lower relative abundance of Bacteroidaceae.
CONCLUSIONS
Our MR analysis suggests that the oral microbiome exerts a causative effect on BC risk, supported by the sequencing data of a case-control study. In the future, studies should be undertaken to comprehensively understand the complex interaction mechanisms between the oral microbiota and BC.
Topics: Female; Humans; Breast Neoplasms; Case-Control Studies; East Asian People; Genome-Wide Association Study; Mendelian Randomization Analysis; Microbiota; Mouth
PubMed: 38485288
DOI: 10.1111/1759-7714.15280 -
BMC Microbiology Jul 2023Non-typeable Haemophilus influenzae (NTHi) has become the major cause of invasive H. influenzae diseases in the post-H. influenzae type b vaccine era. The emergence of...
Molecular characterization of multidrug-resistant non-typeable Haemophilus influenzae with high-level resistance to cefuroxime, levofloxacin, and trimethoprim-sulfamethoxazole.
BACKGROUND
Non-typeable Haemophilus influenzae (NTHi) has become the major cause of invasive H. influenzae diseases in the post-H. influenzae type b vaccine era. The emergence of multidrug-resistant (MDR) NTHi is a growing public health problem. Herein, we investigated the molecular basis of MDR in NTHi. The isolated NTHi were subjected to antimicrobial susceptibility testing for 12 agents. Whole genome and plasmid sequencing were conducted and analyzed to identify significant genetic variations and plasmid-encoded genes conferred antibiotic resistance.
RESULTS
Thirteen (50%) MDR NTHi isolates were obtained; of these, 92.3% were non-susceptible to ampicillin, 30.8% to amoxicillin-clavulanate, 61.5% to cefuroxime, 61.5% to ciprofloxacin/levofloxacin, 92.3% to trimethoprim-sulfamethoxazole, 30.8% to tetracycline, and 7.7% to azithromycin. Eight ampicillin-resistant isolates were β-lactamase positive; of these, 6 carried bla and 2 carried bla, whereas 4 were β-lactamase negative. Genetic variations in mrdA, mepA, and pbpG were correlated with amoxicillin-clavulanate non-susceptibility, whereas variations in ftsI and lpoA conferred cefuroxime resistance. Five variations in gyrA, 2 in gyrB, 3 in parC, 1 in parE, and 1 in the parC-parE intergenic region were associated with levofloxacin/ciprofloxacin non-susceptibility. Among these genes, 8 variations were linked to high-level levofloxacin resistance. Six variations in folA were associated with trimethoprim-sulfamethoxazole resistance. Plasmid-bearing tet(B) and mef(A) genes were responsible for tetracycline and azithromycin resistance in 4 and 1 MDR isolates, respectively.
CONCLUSIONS
This study clarified the molecular epidemiology of MDR in NTHi. This can benefit the monitoring of drug resistance trends in NTHi and the adequate medical management of patients with NTHi infection.
Topics: Humans; Haemophilus influenzae; Cefuroxime; Levofloxacin; Trimethoprim, Sulfamethoxazole Drug Combination; Azithromycin; Microbial Sensitivity Tests; Anti-Bacterial Agents; Ampicillin; Haemophilus Infections; Amoxicillin-Potassium Clavulanate Combination; Tetracycline; Ciprofloxacin; beta-Lactamases
PubMed: 37407940
DOI: 10.1186/s12866-023-02926-6 -
Human Vaccines & Immunotherapeutics Dec 2023A candidate AS01-adjuvanted vaccine containing four surface proteins from non-typable and (NTHi-Mcat) has been developed to help prevent exacerbations of chronic... (Randomized Controlled Trial)
Randomized Controlled Trial
Immunogenicity and safety of the non-typable - (NTHi-Mcat) vaccine administered following the recombinant zoster vaccine versus administration alone: Results from a randomized, phase 2a, non-inferiority trial.
A candidate AS01-adjuvanted vaccine containing four surface proteins from non-typable and (NTHi-Mcat) has been developed to help prevent exacerbations of chronic obstructive pulmonary disease (COPD). Sequential administration of different vaccines containing the same AS01-adjuvant system could lead to immune interference. We compared administration of NTHi-Mcat following AS01-adjuvanted recombinant zoster vaccine (RZV) versus NTHi-Mcat alone. This phase 2a, open-label trial (NCT03894969) randomized healthy current or former smokers (50-80 years) without COPD to administration of NTHi-Mcat at 1, 3 or 6 months after RZV or to NTHi-Mcat alone (2-dose for both vaccines). Primary outcome was non-inferiority of the humoral immune response to NTHi-Mcat administered 1 month after RZV versus NTHi-Mcat alone, evaluated by specific antibody geometric mean concentration (GMC) ratio with 95% confidence intervals (CIs). The per-protocol set included 411 participants. Primary objective was met; lower limit of the 95%CI for the GMC ratio above 0.667 for all four vaccine antigens, 1 month after the second NTHi-Mcat dose. NTHi-Mcat induced similar immune response regardless of whether administered alone or 1, 3 or 6 months following RZV. Safety and reactogenicity profiles were acceptable; adverse event frequency was similar among study groups. Injection site pain was the most common symptom. No new safety concerns were identified. The study demonstrated non-inferiority of the immune response elicited by NTHi-Mcat administered sequentially to RZV versus NTHi-Mcat alone, indicating no immune interference. Starting from 1 month, no specific interval is required between RZV and NTHi-Mcat containing the same AS01-adjuvant system components in different quantities.
Topics: Humans; Haemophilus influenzae; Herpes Zoster; Herpes Zoster Vaccine; Immunogenicity, Vaccine; Moraxella catarrhalis; Pulmonary Disease, Chronic Obstructive; Vaccines, Synthetic
PubMed: 36974988
DOI: 10.1080/21645515.2023.2187194 -
MSystems Dec 2023The usage of 16S rRNA gene sequencing has become the state-of-the-art method for the characterization of the microbiota in health and respiratory disease. The method is...
The usage of 16S rRNA gene sequencing has become the state-of-the-art method for the characterization of the microbiota in health and respiratory disease. The method is reliable for low biomass samples due to prior amplification of the 16S rRNA gene but has limitations as species and certainly strain identification is not possible. However, the usage of metagenomic tools for the analyses of microbiome data from low biomass samples is not straight forward, and careful optimization is needed. In this work, we show that by validating StrainPhlAn 3 results with the data from bacterial cultures, the strain-level tracking of the respiratory microbiome is feasible despite the high content of host DNA being present when parameters are carefully optimized to fit low biomass microbiomes. This work further proposes that strain retention analyses are feasible, at least for more abundant species. This will help to better understand the longitudinal dynamics of the upper respiratory microbiome during health and disease.
Topics: RNA, Ribosomal, 16S; Haemophilus influenzae; Nose; Trachea; Microbiota
PubMed: 37916972
DOI: 10.1128/msystems.00724-23 -
International Journal of Molecular... Jul 2023(APP) is the causative pathogen of porcine pleuropneumonia, a highly contagious respiratory disease in the pig industry. The increasingly severe antimicrobial...
(APP) is the causative pathogen of porcine pleuropneumonia, a highly contagious respiratory disease in the pig industry. The increasingly severe antimicrobial resistance in APP urgently requires novel antibacterial alternatives for the treatment of APP infection. In this study, we investigated the effect of tea polyphenols (TP) against APP. MIC and MBC of TP showed significant inhibitory effects on bacteria growth and caused cellular damage to APP. Furthermore, TP decreased adherent activity of APP to the newborn pig tracheal epithelial cells (NPTr) and the destruction of the tight adherence junction proteins β-catenin and occludin. Moreover, TP improved the survival rate of APP infected mice but also attenuated the release of the inflammation-related cytokines IL-6, IL-8, and TNF-α. TP inhibited activation of the TLR/MAPK/PKC-MLCK signaling for down-regulated TLR-2, TLR4, p-JNK, p-p38, p-PKC-α, and MLCK in cells triggered by APP. Collectively, our data suggest that TP represents a promising therapeutic agent in the treatment of APP infection.
Topics: Animals; Swine; Mice; Pleuropneumonia; Actinobacillus pleuropneumoniae; Toll-Like Receptor 4; Actinobacillus; Tight Junctions; Lung; Actinobacillus Infections; Mycoplasma Infections; Tea; Swine Diseases
PubMed: 37511601
DOI: 10.3390/ijms241411842 -
Scientific Reports Aug 2023The COVID-19 pandemic and resulting public health directives led to many changes in families' social and material environments. Prior research suggests that these...
The COVID-19 pandemic and resulting public health directives led to many changes in families' social and material environments. Prior research suggests that these changes are likely to impact composition of the gut microbiome, particularly during early childhood when the gut microbiome is developing most rapidly. Importantly, disruption to the gut microbiome during this sensitive period can have potentially long-lasting impacts on health and development. In the current study, we compare gut microbiome composition among a socioeconomically and racially diverse group of 12-month old infants living in New York City who provided stool samples before the pandemic (N = 34) to a group who provided samples during the first 9-months of the pandemic (March-December 2020; N = 20). We found that infants sampled during the pandemic had lower alpha diversity of the microbiome, lower abundance of Pasteurellaceae and Haemophilus, and significantly different beta diversity based on unweighted Unifrac distance than infants sampled before the pandemic. Exploratory analyses suggest that gut microbiome changes due to the pandemic occurred relatively quickly after the start of the pandemic and were sustained. Our results provide evidence that pandemic-related environmental disruptions had an impact on community-level taxonomic diversity of the developing gut microbiome, as well as abundance of specific members of the gut bacterial community.
Topics: Child, Preschool; Humans; Infant; COVID-19; Gastrointestinal Microbiome; Microbiota; Pandemics
PubMed: 37587195
DOI: 10.1038/s41598-023-40102-y -
Gut Microbes 2024The multi-factorial involvement of gut microbiota with Crohn's disease (CD) necessitates robust analysis to uncover possible associations with particular microbes. CD...
The multi-factorial involvement of gut microbiota with Crohn's disease (CD) necessitates robust analysis to uncover possible associations with particular microbes. CD has been linked to specific bacteria, but reported associations vary widely across studies. This inconsistency may result from heterogeneous associations across individual patients, resulting in no apparent or only weak relationships with the means of bacterial abundances. We investigated the relationship between bacterial relative abundances and disease activity in a longitudinal cohort of CD patients ( = 57) and healthy controls ( = 15). We applied quantile regression, a statistical technique that allows investigation of possible relationships outside the mean response. We found several significant and mostly negative associations with CD, especially in lower quantiles of relative abundance on family or genus level. Associations found by quantile regression deviated from the mean response in relative abundances of Coriobacteriaceae, Pasteurellaceae, Peptostreptococcaceae, Prevotellaceae, and Ruminococcaceae. For the family Streptococcaceae we found a significant elevation in relative abundance for patients experiencing an exacerbation relative to those who remained without self-reported symptoms or measurable inflammation. Our analysis suggests that specific bacterial families are related to CD and exacerbation, but associations vary between patients due to heterogeneity in disease course, medication history, therapy response, gut microbiota composition and historical contingency. Our study underscores that microbial diversity is reduced in the gut of CD patients, but suggests that the process of diversity loss is rather irregular with respect to specific taxonomic groups. This novel insight may advance our ecological understanding of this complex disease.
Topics: Humans; Crohn Disease; Gastrointestinal Microbiome; Inflammation; Bacteria; Bacteroidetes
PubMed: 38105519
DOI: 10.1080/19490976.2023.2292239 -
Infection and Immunity Sep 2023is a causative agent of cutaneous ulcers in children who live in the tropics and of the genital ulcer disease chancroid in sexually active persons. In the anaerobic...
is a causative agent of cutaneous ulcers in children who live in the tropics and of the genital ulcer disease chancroid in sexually active persons. In the anaerobic environment of abscesses and ulcers, anaerobic respiration and mixed acid fermentation (MAF) can be used to provide cellular energy. In , MAF produces formate, acetate, lactate, succinate, and ethanol; however, MAF has not been studied in . In human challenge experiments with 35000HP, transcripts of the formate transporter FocA and pyruvate formate lyase (PflB) were upregulated in pustules compared to the inocula. We made single and double mutants of and in 35000HP. Growth of 35000HPΔ was similar to 35000HP, but 35000HPΔ and 35000HPΔ had growth defects during both aerobic and anaerobic growth. Mutants lacking did not secrete formate into the media. However, formate was secreted into the media by 35000HPΔ, indicating that has alternative formate transporters. The pH of the media during anaerobic growth decreased for 35000HP and 35000HPΔ, but not for 35000HPΔ or 35000HPΔ, indicating that is the main contributor to media acidification during anaerobic growth. We tested whether formate production and transport were required for virulence in seven human volunteers in a mutant versus parent trial between 35000HPΔ and 35000HP. The pustule formation rate was similar for 35000HP (42.9%)- and 35000HPΔ (62%)-inoculated sites. Although formate production occurs during growth and transcripts are upregulated during human infection, and are not required for virulence in humans.
Topics: Child; Humans; Haemophilus ducreyi; Virulence; Ulcer; Healthy Volunteers; Formates; Escherichia coli; Membrane Transport Proteins; Escherichia coli Proteins
PubMed: 37594273
DOI: 10.1128/iai.00176-23 -
Journal of Global Antimicrobial... Dec 2023The aim of this study was to characterize the floR-carrying plasmids originating from Glaesserella parasuis and Actinobacillus indolicus isolated from pigs with...
OBJECTIVES
The aim of this study was to characterize the floR-carrying plasmids originating from Glaesserella parasuis and Actinobacillus indolicus isolated from pigs with respiratory disease in China.
METHODS
A total of 125 G. parasuis and 28 A. indolicus strains collected between 2009 and 2022 were screened for florfenicol resistance. Characterization of floR-positive isolates and plasmids were determined by antimicrobial susceptibility testing, serotyping, multilocus sequence typing (MLST), conjugation and transformation assays, whole-genome sequencing (WGS), and phylogenetic analysis.
RESULTS
One A. indolicus and six G. parasuis were identified as positive for floR. The six G. parasuis were assigned to four different serovars, including serovars 6, 7, 9, and unknown. In addition to strain XP11, six floR genes were located on plasmids. The six floR-bearing plasmids could be transformed into Pasteurella multocida and divided into two different types, including ∼5000 bp and ∼6000 bp plasmids. The ∼5000 bp plasmids consisting of rep, lysR, mobB, and floR genes, exhibited high similarity among Pasteurellaceae bacteria. Furthermore, the ∼6000 bp plasmids, consisting of rep, lysR, mobC, mobA/L, and floR genes, showed high similarity between G. parasuis and Actinobacillus Spp. Notably, WGS results showed that the floR modules of the two types of plasmids could be transferred and integrated into the diverse Pasteurellaceae- origined plasmids.
CONCLUSION
This study firstly reported the characterization of floR-carrying plasmids from A. indolicus and a non-virulent serovar of G. parasuis in pigs in China and elucidated the transmission mechanism of the floR resistance gene among the Pasteurellaceae family.
Topics: Animals; Swine; Anti-Bacterial Agents; Multilocus Sequence Typing; Phylogeny; Plasmids; Actinobacillus
PubMed: 37726088
DOI: 10.1016/j.jgar.2023.09.009 -
Nature Communications Oct 2023The sudden mortality of African elephants (Loxodonta africana) in Botswana and Zimbabwe in 2020 provoked considerable public interest and speculation. Poaching and...
The sudden mortality of African elephants (Loxodonta africana) in Botswana and Zimbabwe in 2020 provoked considerable public interest and speculation. Poaching and malicious poisoning were excluded early on in the investigation. Other potential causes included environmental intoxication, infectious diseases, and increased habitat stress due to ongoing drought. Here we show evidence of the mortalities in Zimbabwe as fatal septicaemia associated with Bisgaard taxon 45, an unnamed close relative of Pasteurella multocida. We analyse elephant carcasses and environmental samples, and fail to find evidence of cyanobacterial or other intoxication. Post-mortem and histological findings suggest a bacterial septicaemia similar to haemorrhagic septicaemia caused by P. multocida. Biochemical tests and 16S rDNA analysis of six samples and genomic analysis of one sample confirm the presence of Bisgaard taxon 45. The genome sequence contains many of the canonical P. multocida virulence factors associated with a range of human and animal diseases, including the pmHAS gene for hyaluronidase associated with bovine haemorrhagic septicaemia. Our results demonstrate that Bisgaard taxon 45 is associated with a generalised, lethal infection and that African elephants are susceptible to opportunistically pathogenic Pasteurella species. This represents an important conservation concern for elephants in the largest remaining metapopulation of this endangered species.
Topics: Humans; Animals; Cattle; Hemorrhagic Septicemia; Elephants; Pasteurella; Pasteurella multocida; Ecosystem
PubMed: 37880229
DOI: 10.1038/s41467-023-41987-z