-
European Archives of... Jun 2024The nasal cavity and gut are interconnected, both housing a rich natural microbiome. Gut microbiota may interact with nasal microbiota and contribute to the development...
BACKGROUND
The nasal cavity and gut are interconnected, both housing a rich natural microbiome. Gut microbiota may interact with nasal microbiota and contribute to the development of chronic rhinosinusitis (CRS). However, the specific role of gut microbiota in CRS has not been fully investigated. Therefore, we conducted a two-sample Mendelian randomization study to reveal the potential genetic causal effect of gut microbiota on CRS.
METHODS
We performed a two-sample Mendelian Randomization (MR) analysis using aggregated data from genome-wide association studies (GWAS) on gut microbiota and CRS. The primary method used to assess the causal relationship between gut microbiota and CRS was the inverse variance weighting (IVW) method. In addition, sensitivity analyses were conducted to evaluate the robustness of the MR results, including heterogeneity, pleiotropy, and leave-one-out tests.
RESULTS
Genetically predicted twelve gut microbiota, including class Coriobacteriia, class Methanobacteria, family Coriobacteriaceae, family Methanobacteriaceae, family Pasteurellaceae, genus Haemophilus, genus Ruminococcus torques group, genus Subdoligranulum, order Coriobacteriales, order Methanobacteriales, order Pasteurellales, and phylum Proteobacteria, demonstrated a potential inhibitory effect on CRS risk (P < 0.05). In addition, four gut microbiota, including family Streptococcaceae, genus Clostridium innocuum group, genus Oscillospira, and genus Ruminococcaceae NK4A214 group, exhibited a causal role in increasing CRS risk (P < 0.05). Sensitivity analyses showed no evidence of heterogeneity or pleiotropy (P > 0.05).
CONCLUSIONS
This study reveals the causal relationship between specific gut microbiota and CRS, which provides a new direction and theoretical foundation for the future development of interventions and prevention and treatment strategies for CRS.
Topics: Humans; Sinusitis; Rhinitis; Mendelian Randomization Analysis; Chronic Disease; Gastrointestinal Microbiome; Genome-Wide Association Study; Rhinosinusitis
PubMed: 38340160
DOI: 10.1007/s00405-024-08468-5 -
The Pediatric Infectious Disease Journal Aug 2023Young children with acute otitis media (AOM) frequently exhibit nasopharyngeal colonization with either Streptococcus pneumoniae, Haemophilus influenzae or both... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Young children with acute otitis media (AOM) frequently exhibit nasopharyngeal colonization with either Streptococcus pneumoniae, Haemophilus influenzae or both pathogens. We aimed to determine if antibiotics could be spared or shortened in those without nasopharyngeal colonization with either pathogen.
METHODS
In 2 separate randomized clinical trials in children aged 6-23 months with stringently-diagnosed AOM, we performed bacterial cultures on nasopharyngeal specimens collected at the time of diagnosis. In the first trial, we compared the efficacy of amoxicillin/clavulanate (amox/clav) administered for 10 days vs. that of placebo, and in the second trial, we compared the efficacy of amox/clav administered for 10 days vs. 5 days. In each trial, we classified children as being colonized with both S. pneumoniae and H. influenzae, S. pneumoniae alone, H. influenzae alone, or neither pathogen, and as experiencing either clinical success or clinical failure at the end-of-therapy visit, based on previously reported a priori criteria.
RESULTS
We evaluated 796 children. Among children randomized to amox/clav, those colonized with either S. pneumoniae or H. influenzae or both were approximately twice as likely to experience clinical failure as children not colonized with either pathogen (odds ratio: 1.8; confidence intervals: 1.2-2.9). In contrast, among children randomized to placebo, clinical failure at the end-of-therapy visit was not associated with nasopharyngeal culture results at the time of diagnosis.
CONCLUSIONS
Children colonized with either S. pneumoniae or H. influenzae or both have a greater chance of treatment failure than children colonized with neither pathogen.
Topics: Child; Humans; Infant; Child, Preschool; Otitis Media; Anti-Bacterial Agents; Amoxicillin-Potassium Clavulanate Combination; Treatment Failure; Streptococcus pneumoniae; Acute Disease; Haemophilus influenzae; Nasopharynx
PubMed: 37171965
DOI: 10.1097/INF.0000000000003956 -
Frontiers in Cellular and Infection... 2023is a widespread zoonotic pathogen that causes severe damage to the poultry industry. This study focused on the antibacterial effects and mechanism of action of...
OBJECTIVE
is a widespread zoonotic pathogen that causes severe damage to the poultry industry. This study focused on the antibacterial effects and mechanism of action of coptisine against .
METHODS
The minimum inhibitory concentration and half maximal inhibitory concentration of coptisine against was measured. Additionally, the effect of coptisine on growth, cell wall, activity of respiratory enzymes, soluble protein content and DNA synthesis were also analyzed. Finally, the effect of coptisine on gene transcription was determined using RNA sequencing.
RESULTS
We demonstrated that coptisine has a strong antibacterial effect against , with a minimum inhibitory concentration of 0.125 mg/mL. Moreover, the measurement of the half maximal inhibitory concentration confirmed that coptisine was safe for the pathogen. The growth curve showed that coptisine inhibited bacterial growth. Measurement of alkaline phosphatase activity in the culture solution showed that coptisine affected cell wall permeability. Transmission electron microscopy revealed that coptisine chloride destroyed the cell structure. In addition, coptisine blocked the respiratory system, as measured by the levels of critical enzymes of the tricarboxylic acid cycle and glycolysis, succinate dehydrogenase and lactate dehydrogenase, respectively. Similarly, coptisine inhibited the synthesis of soluble proteins and genomic DNA. The KEGG pathway analysis of the differentially expressed genes showed that they were associated with cellular, respiratory, and amino acid metabolism, which were downregulated after coptisine treatment. Additionally, genes related to RNA degradation and the aminoacyl-tRNA pathway were upregulated.
CONCLUSION
In this study, we demonstrated that coptisine exerts an antibacterial effect on . These findings suggest that coptisine has a multifaceted impact on various pathways, resulting in the inhibition of . Thus, coptisine is a potential alternative to antibiotics for the treatment of infections in a clinical setting.
Topics: Humans; Pasteurella multocida; Pasteurella Infections; Anti-Bacterial Agents; Berberine
PubMed: 37502603
DOI: 10.3389/fcimb.2023.1207855 -
Pharmacological Research Jun 2024Studies have shown that the microbiota-gut-brain axis is highly correlated with the pathogenesis of depression in humans. However, whether independent oral microbiome...
Studies have shown that the microbiota-gut-brain axis is highly correlated with the pathogenesis of depression in humans. However, whether independent oral microbiome that do not depend on gut microbes could affect the progression of depression in human beings remains unclear, neither does the presence and underlying mechanisms of the microbiota-oral-brain axis in the development of the condition. Hence this study that encompasses clinical and animal experiments aims at investigating the correlation between oral microbiota and the onset of depression via mediating the microbiota-oral-brain axis. We compared the oral microbial compositions and metabolomes of 87 patients with depressive symptoms versus 70 healthy controls. We found that the oral microbial and metabolic signatures were significantly different between the two groups. Significantly, germ-free (GF) mice transplanted with saliva from mice exposing to chronic restraint stress (CRS) displayed depression-like behavior and oral microbial dysbiosis. This was characterized by a significant differential abundance of bacterial species, including the enrichment of Pseudomonas, Pasteurellaceae, and Muribacter, as well as the depletion of Streptococcus. Metabolomic analysis showed the alternation of metabolites in the plasma of CRS-exposed GF mice, especially Eicosapentaenoic Acid. Furthermore, oral and gut barrier dysfunction caused by CRS-induced oral microbiota dysbiosis may be associated with increased blood-brain barrier permeability. Pseudomonas aeruginosa supplementation exacerbated depression-like behavior, while Eicosapentaenoic Acid treatment conferred protection against depression-like states in mice. These results suggest that oral microbiome and metabolic function dysbiosis may be relevant to the pathogenesis and pathophysiology of depression. The proposed microbiota-oral-brain axis provides a new way and targets for us to study the pathogenesis of depression.
Topics: Animals; Dysbiosis; Depression; Male; Humans; Stress, Psychological; Female; Adult; Mice; Restraint, Physical; Mice, Inbred C57BL; Gastrointestinal Microbiome; Brain-Gut Axis; Mouth; Middle Aged; Saliva; Behavior, Animal; Blood-Brain Barrier
PubMed: 38763328
DOI: 10.1016/j.phrs.2024.107214 -
Respiratory Physiology & Neurobiology Sep 2023Pasteurella (P.) multocida commonly occurs in the upper respiratory tract of healthy domestic pets, especially cats and dogs. People become infected by biting,...
BACKGROUND
Pasteurella (P.) multocida commonly occurs in the upper respiratory tract of healthy domestic pets, especially cats and dogs. People become infected by biting, scratching or direct contact with the animal's saliva. Inflammation develops in the wound and limits itself to the skin and subcutaneous tissue. P. multocida may cause respiratory tract infections and severe life-threatening complications. The study aimed to identify the lower respiratory infection in humans caused by P. multocida, to determine the potential source of infection and the associated symptoms, comorbidities and applied treatment.
MATERIALS AND METHODS
Between January 2010 and September 2021, 14,258 patients underwent 16,255 routine flexible video bronchoscopy (FVB), and the same number of bronchoalveolar lavage fluid (BALF) samples for microbiological examination were taken.
RESULTS
Microbiological examinations of the BALF only allowed the identification of six patients with P. multocida infection. All persons reported multiple scratches or bites and licking or kissing by their pets in the past. Productive cough with expectoration of mucopurulent discharge was the predominant symptom.
CONCLUSIONS
A lower respiratory infection caused by P. multocida is not common in humans. It should be considered particularly in elderly patients with underlying diseases and exposure to cats and dogs.
Topics: Humans; Animals; Cats; Dogs; Aged; Pasteurella multocida; Pasteurella Infections; Pasteurella; Respiratory Tract Infections; Saliva
PubMed: 37331420
DOI: 10.1016/j.resp.2023.104091 -
International Journal of Systematic and... Oct 2023Forty-one isolates of Bisgaard taxon 6 obtained from guinea pigs, pandas, pigs and muskrat and isolates of taxon 10 from horses and horse bites in humans were subjected...
Forty-one isolates of Bisgaard taxon 6 obtained from guinea pigs, pandas, pigs and muskrat and isolates of taxon 10 from horses and horse bites in humans were subjected phenotypic characterization. Production of acid from (-)-d-mannitol, (-)-d-sorbitol and (+)-d-glycogen separated taxon 10 (positive) from taxon 6 (negative), while from two to 11 phenotypic characteristics separated taxa 6 and 10 from the 32 genera of reported so far. Forty-four strains were genetically characterized. Sequencing of 16S rRNA genes documented a monophyletic relationship at the species level and the highest 16S rRNA gene sequence similarity of 95.6 % to other species was found between strain CCUG 15568 and the type strain of (CCUG 38457). Digital DNA-DNA hybridization (dDDH) values predicted from whole genomic sequences between CCUG 15568 and other characterized strains of taxa 6 and 10 were 69.3-99.9 %. The average nucleotide identity values were higher than 95 % for all strains. The highest dDDH value of 29 % outside the taxa 6 and 10 group was obtained with the genome of the type strain of [] , indicating a separate taxonomic status at species level to taxa 6 and 10. The phylogenetic comparison of concatenated conserved protein sequences showed the unique position of the taxa investigated in the current study which qualified for the status of a new genus since the highest identity was found with with 79 %, well below the upper threshold between genera of 85 %. Based upon the low genetic similarity to other genera of the family and a unique phenotype, we suggest that Bisgaard taxa 6 and 10 should be classified as gen. nov., sp. nov. The G+C of the type strain of , 8.5 (=CCUG 15568=DSM 115565), is 46.2 mol%, calculated from the whole genome.
Topics: Humans; Animals; Guinea Pigs; Horses; Phylogeny; RNA, Ribosomal, 16S; Sequence Analysis, DNA; DNA, Bacterial; Bacterial Typing Techniques; Base Composition; Fatty Acids; Pasteurellaceae
PubMed: 37882672
DOI: 10.1099/ijsem.0.006092 -
Retinal Cases & Brief Reports Jan 2024To describe a rare case of unilateral, endogenous endophthalmitis caused by Aggregatibacter aphrophilus (HACEK group) confirmed in vitreous and blood cultures, in a...
PURPOSE
To describe a rare case of unilateral, endogenous endophthalmitis caused by Aggregatibacter aphrophilus (HACEK group) confirmed in vitreous and blood cultures, in a patient with dentophobia.
METHODS
Case report.
PATIENTS
A seventy-five-year-old male patient with Type 2 diabetes, previous myocardial infarction, and pacemaker implantation.
RESULTS
Patient was observed with sudden loss of vision at the Department of Ophthalmology, Uppsala University. Initial diagnosis was posterior vitreous detachment and anterior uveitis, but progression of disease led to vitrectomy, which actually demonstrated endophthalmitis and growth of A. aphrophilus of the HACEK group. Aggregatibacter bacteremia and pacemaker endocarditis were also identified and dental examination confirmed growth of Aggregatibacter in the oral cavity. Intravitreal treatment with ceftazidime and vancomycin according to Endophthalmitis Vitrectomy Study protocol was administered with quick resolution of endophthalmitis.
CONCLUSION
Aggregatibacter endophthalmitis is a rare, but devastating cause of vision loss where immediate diagnosis may be delayed. Prompt diagnosis may be facilitated by a thorough medical history and early vitreous biopsy. Systemic investigation by an infectious disease specialist and multidisciplinary assessment are mandatory. Ophthalmologic treatment is effective with intravitreal injections of ceftazidime and vancomycin.
Topics: Male; Humans; Aged; Ceftazidime; Anti-Bacterial Agents; Vancomycin; Aggregatibacter; Diabetes Mellitus, Type 2; Dental Anxiety; Endophthalmitis; Vitrectomy; Eye Infections, Bacterial
PubMed: 36007190
DOI: 10.1097/ICB.0000000000001335 -
Virulence Dec 2024(APP) is an important pathogen of the porcine respiratory disease complex, which leads to huge economic losses worldwide. We previously demonstrated that -producing...
(APP) is an important pathogen of the porcine respiratory disease complex, which leads to huge economic losses worldwide. We previously demonstrated that -producing bovine neutrophil β-defensin-5 (B5) could resist the infection by the bovine intracellular pathogen . In this study, the roles of synthetic B5 in regulating mucosal innate immune response and protecting against extracellular APP infection were further investigated using a mouse model. Results showed that B5 promoted the production of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and interferon (IFN)-β in macrophages as well as dendritic cells (DC) and enhanced DC maturation . Importantly, intranasal B5 was safe and conferred effective protection against APP via reducing the bacterial load in lungs and alleviating pulmonary inflammatory damage. Furthermore, in the early stage of APP infection, we found that intranasal B5 up-regulated the secretion of TNF-α, IL-1β, IL-17, and IL-22; enhanced the rapid recruitment of macrophages, neutrophils, and DC; and facilitated the generation of group 3 innate lymphoid cells in lungs. In addition, B5 activated signalling pathways associated with cellular response to IFN-β and activation of innate immune response in APP-challenged lungs. Collectively, B5 via the intranasal route can effectively ameliorate the immune suppression caused by early APP infection and provide protection against APP. The immunization strategy may be applied to animals or human respiratory bacterial infectious diseases. Our findings highlight the potential importance of B5, enhancing mucosal defence against intracellular bacteria like APP which causes early-phase immune suppression.
Topics: Humans; Swine; Animals; Cattle; Immunity, Innate; Actinobacillus pleuropneumoniae; Lymphocytes; Lung; Tumor Necrosis Factor-alpha; Immunosuppression Therapy
PubMed: 38378464
DOI: 10.1080/21505594.2024.2316459 -
Journal of Periodontology Jun 2024This study determined the prevalence of aggressive (molar-incisor pattern) (Ag/MI) periodontitis and assessed the associated subgingival bacterial-herpesvirus microbiota...
BACKGROUND
This study determined the prevalence of aggressive (molar-incisor pattern) (Ag/MI) periodontitis and assessed the associated subgingival bacterial-herpesvirus microbiota in Pueblo Indian adolescents in the southwestern United States.
METHODS
The study included 240 Pueblo Indian adolescents, aged 13-20 years old, residing in three Rio Grande River villages in New Mexico and the Hopi Pueblo reservation in Arizona. Adolescents with Ag/MI periodontitis or periodontal health provided subgingival samples for culture of bacterial pathogens and for polymerase chain reaction detection of periodontal herpesviruses.
RESULTS
Ag/MI periodontitis was detected in 22 (9.2%) Pueblo Indian adolescents, with 21 exhibiting a localized molar-incisor breakdown pattern. Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and other red/orange complex bacterial pathogens predominated in Ag/MI periodontitis, whereas periodontal health yielded mainly viridans streptococci and Actinomyces species. Periodontal herpesviruses demonstrated a 3.5 odds ratio relationship with Ag/MI periodontitis. The only adolescent with generalized Ag/MI periodontitis harbored viral co-infection by cytomegalovirus plus Epstein-Barr virus Type 1, in addition to A. actinomycetemcomitans, P. gingivalis, and several other periodontopathic bacteria.
CONCLUSIONS
Pueblo Indian adolescents showed an unusually high prevalence of early-age Ag/MI periodontitis predominated by periodontopathic bacteria and herpesviruses suspected to be major etiologic agents of the disease.
Topics: Humans; Adolescent; Young Adult; Male; Female; Aggressive Periodontitis; Indians, North American; Aggregatibacter actinomycetemcomitans; Porphyromonas gingivalis; Arizona; New Mexico; Cytomegalovirus; Actinomyces; Viridans Streptococci; Prevalence; Coinfection; Herpesvirus 4, Human; Herpesviridae
PubMed: 37910464
DOI: 10.1002/JPER.23-0410 -
Veterinary Research Jul 2023Actinobacillus pleuropneumoniae (APP) is a gram-negative pathogenic bacterium responsible for porcine contagious pleuropneumonia (PCP), which can cause porcine...
TurboID screening of ApxI toxin interactants identifies host proteins involved in Actinobacillus pleuropneumoniae-induced apoptosis of immortalized porcine alveolar macrophages.
Actinobacillus pleuropneumoniae (APP) is a gram-negative pathogenic bacterium responsible for porcine contagious pleuropneumonia (PCP), which can cause porcine necrotizing and hemorrhagic pleuropneumonia. Actinobacillus pleuropneumoniae-RTX-toxin (Apx) is an APP virulence factor. APP secretes a total of four Apx toxins, among which, ApxI demonstrates strong hemolytic activity and cytotoxicity, causing lysis of porcine erythrocytes and apoptosis of porcine alveolar macrophages. However, the protein interaction network between this toxin and host cells is still poorly understood. TurboID mediates the biotinylation of endogenous proteins, thereby targeting specific proteins and local proteomes through gene fusion. We applied the TurboID enzyme-catalyzed proximity tagging method to identify and study host proteins in immortalized porcine alveolar macrophage (iPAM) cells that interact with the exotoxin ApxI of APP. His-tagged TurboID-ApxIA and TurboID recombinant proteins were expressed and purified. By mass spectrometry, 318 unique interacting proteins were identified in the TurboID ApxIA-treated group. Among them, only one membrane protein, caveolin-1 (CAV1), was identified. A co-immunoprecipitation assay confirmed that CAV1 can interact with ApxIA. In addition, overexpression and RNA interference experiments revealed that CAV1 was involved in ApxI toxin-induced apoptosis of iPAM cells. This study provided first-hand information about the proteome of iPAM cells interacting with the ApxI toxin of APP through the TurboID proximity labeling system, and identified a new host membrane protein involved in this interaction. These results lay a theoretical foundation for the clinical treatment of PCP.
Topics: Swine; Animals; Actinobacillus pleuropneumoniae; Macrophages, Alveolar; Exotoxins; Apoptosis; Membrane Proteins; Bacterial Proteins; Actinobacillus Infections; Hemolysin Proteins; Swine Diseases
PubMed: 37475032
DOI: 10.1186/s13567-023-01194-6