-
Euro Surveillance : Bulletin Europeen... Apr 2024We report a record high pertussis epidemic in Denmark since August 2023. Highest incidence was in adolescents, while peak incidence in infants was lower vs previous...
We report a record high pertussis epidemic in Denmark since August 2023. Highest incidence was in adolescents, while peak incidence in infants was lower vs previous epidemics in 2019 and 2016. Among infants aged 0-2 months, over half (29/48) were hospitalised and one infant died, underlining the disease severity in the youngest. To protect infants, pertussis vaccination in pregnant women was introduced in January 2024 in the national vaccination programme. Improved vaccination surveillance in pregnant women is being implemented.
Topics: Infant; Adolescent; Humans; Female; Pregnancy; Whooping Cough; Bordetella pertussis; Vaccination; Pregnant Women; Incidence; Denmark; Pertussis Vaccine
PubMed: 38577803
DOI: 10.2807/1560-7917.ES.2024.29.14.2400160 -
Frontiers in Oncology 2024This study employs a two-sample bidirectional Mendelian randomization (MR) approach to systematically evaluate the causal relationship between gut microbiota and oral...
UNLABELLED
This study employs a two-sample bidirectional Mendelian randomization (MR) approach to systematically evaluate the causal relationship between gut microbiota and oral cavity cancer (OCC).
OBJECTIVE
To address the challenge in establishing the causal relationship between gut microbiota and OCC, we applied a systematic MR analysis.
METHODS
Utilizing GWAS data from the MiBioGen consortium (18,340 individuals) and UK Biobank (n = 264,137), we selected instrumental variables and employed MR-Egger, weighted median, IVW, and weighted mode analyses. Heterogeneity and pleiotropy were assessed using Cochran's Q test and MR-Egger intercept test.
RESULTS
Our findings indicate, at the order level, (OR = 0.9990, 95% CI = 0.9980-1.0000, = ), (OR = 1.0009, 95% CI = 1.0001-1.0018, = ), and (OR = 0.9979, 95% CI = 0.9962-0.9995, = ) exhibit causality on OCC in the Weighted median, IVW, and MR-Egger analyses, respectively. At the family level, (OR = 1.0012, 95% CI = 1.0004-1.0019, = ) and (OR = 0.9970, 95% CI = 0.9948-0.9992, = ) show causality on OCC in IVW and MR-Egger analyses. At the genus level, (IVW, OR = 0.9987, 95% CI = 0.9980-0.9995, = ; MR-Egger, OR = 0.9978, 95% CI = 0.9962-0.9995, = ), (IVW, OR = 1.0008, 95% CI = 1.0001-1.0015, = ), (IVW, OR = 0.9995, 95% CI = 0.9990-1.0000, = ), group (IVW, OR = 1.0005, 95% CI = 1.0000-1.0009, = ), and (IVW, OR = 0.9994, 95% CI = 0.9989-0.9999, = ) are implicated in causing OCC in related analyses.
CONCLUSION
Our study identifies order, family, genus, and group as causally increasing OCC risk. In contrast, order, order, family, genus, genus, and genus are causally associated with a decreased OCC risk. However, further investigations are essential to delineate an optimal gut microbiota composition and unravel the underlying mechanisms of specific bacterial taxa in OCC pathophysiology.
PubMed: 38884080
DOI: 10.3389/fonc.2024.1389678 -
Heliyon Feb 2024Autoimmune thyroiditis (AIT), also known as Hashimoto's thyroiditis (HT) or chronic lymphocytic thyroiditis, is a prevalent autoimmune disorder. Despite its high...
BACKGROUND
Autoimmune thyroiditis (AIT), also known as Hashimoto's thyroiditis (HT) or chronic lymphocytic thyroiditis, is a prevalent autoimmune disorder. Despite its high prevalence, the pathogenesis of AIT remains unclear. Previous studies have suggested a potential association between gut microbiota and AIT. However, whether this relationship is causal or coincidental remains uncertain. To address this gap in knowledge, our study aimed to investigate the potential causal association between gut microbiota and AIT using the two-sample Mendelian randomization (MR) method.
METHODS
Summary-level gut microbiota data comprising 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla) were obtained from the comprehensive MiBioGen study. Genetic associations with 22 gastrointestinal diseases were extracted from the UK Biobank, FinnGen study, and various extensive GWAS studies. A meticulous MR analysis was conducted to evaluate the causal relationship between genetically predicted gut microbiota and these gastrointestinal diseases. Sensitivity analyses and tests for heterogeneity were systematically performed to validate the reliability of our findings.
RESULTS
Six gut microbiota species showed significant associations with AIT according to the IVW method. Among them, the following exhibited negative associations with AIT: family Alcaligenaceae, family Pasteurellaceae (ID: 3689), family Peptococcaceae, genus Lachnospira, genus Victivallis, and order Pasteurellales (ID: 3688). No evidence of pleiotropy or heterogeneity was detected.
CONCLUSION
The MR analysis uncovered a causal relationship at the genetic prediction level between specific gut microbiota and AIT. These findings offer novel insights into the mechanisms governing the development of AIT mediated by gut microbiota. This knowledge could inform the design of future interventions, potentially involving microbiome-related strategies, to address the mechanisms associated with AIT development.
PubMed: 38356548
DOI: 10.1016/j.heliyon.2024.e25652 -
Frontiers in Cellular and Infection... 2024Previous studies have suggested a link between gut microbiota and skin diseases, including erysipelas, an inflammatory skin condition. Despite this, the precise nature...
BACKGROUND
Previous studies have suggested a link between gut microbiota and skin diseases, including erysipelas, an inflammatory skin condition. Despite this, the precise nature of the relationship between erysipelas and gut microbiota remains unclear and subject to debate.
METHODS
We conducted a Mendelian Randomization (MR) analysis using publicly available summary data from genome-wide association studies (GWAS) to explore the potential causal relationship between gut microbiota and erysipelas. Instrumental variables (IVs) were identified using a comprehensive set of screening methods. We then performed MR analyses primarily using the Inverse Variance Weighted (IVW) method, complemented by alternative approaches such as MR Egger, weighted median, simple mode, and weighted mode. A series of sensitivity analyses, including Cochran's Q test, MR-Egger intercept test, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test, and a leave-one-out test, were executed to ensure the robustness and validity of our findings.
RESULTS
We identified potential associations between erysipelas and various gut microbiota, including (OR 1.23; 95% CI 1.06-1.43; p=0.006), (OR 0.77; 95% CI 0.67-0.90; p=0.001), and others. Notably, associations with , , , , , and were also observed. Sensitivity analyses confirmed the robustness of these associations.
CONCLUSION
Our MR analysis suggests both potentially beneficial and harmful causal relationships between various gut microbiota and the incidence of erysipelas. This study provides new theoretical and empirical insights into the pathogenesis of erysipelas and underscores the potential for innovative preventive and therapeutic approaches.
Topics: Humans; Erysipelas; Mendelian Randomization Analysis; Gastrointestinal Microbiome; Genome-Wide Association Study; Skin; Bacteroidetes; Clostridiales
PubMed: 38638831
DOI: 10.3389/fcimb.2024.1371591 -
and activity of cefiderocol against spp. and complex, including carbapenem-non-susceptible isolates.Antimicrobial Agents and Chemotherapy Dec 2023spp. and complex (Bcc) are rare but diverse opportunistic pathogens associated with serious infections, which are often multidrug resistant. This study compared the...
spp. and complex (Bcc) are rare but diverse opportunistic pathogens associated with serious infections, which are often multidrug resistant. This study compared the antibacterial activity of the siderophore antibiotic cefiderocol against spp. and Bcc isolates with that of other approved antibacterial drugs, including ceftazidime-avibactam, ciprofloxacin, colistin, imipenem-relebactam, and meropenem-vaborbactam. Isolates were collected in the SIDERO multinational surveillance program. Among 334 spp. isolates [76.6% from respiratory tract infections (RTIs)], cefiderocol had minimum inhibitory concentration (MIC) of 0.06/0.5 µg/mL overall and 0.5/4 µg/mL against 52 (15.6%) carbapenem-non-susceptible (Carb-NS) isolates. Eleven (3.3%) spp. isolates overall and 6 (11.5%) Carb-NS isolates were not susceptible to cefiderocol. Among 425 Bcc isolates (73.4% from RTIs), cefiderocol had MIC of ≤0.03/0.5 µg/mL overall and ≤0.03/1 µg/mL against 184 (43.3%) Carb-NS isolates. Twenty-two (5.2%) Bcc isolates overall and 13 (7.1%) Carb-NS isolates were not susceptible to cefiderocol. Cumulative MIC distributions showed cefiderocol to be the most active of the agents tested against both spp. and Bcc. In a neutropenic murine lung infection model and a humanized pharmacokinetic immunocompetent rat lung infection model, cefiderocol showed significant bactericidal activity against two meropenem-resistant strains compared with untreated controls ( < 0.05) and vehicle-treated controls ( < 0.05), respectively. Meropenem, piperacillin-tazobactam, ceftazidime, and ciprofloxacin comparators showed no significant activity in these models. The results suggest that cefiderocol could be a possible treatment option for RTIs caused by spp. and Bcc.
Topics: Rats; Animals; Mice; Cefiderocol; Meropenem; Carbapenems; Cephalosporins; Burkholderia cepacia complex; Achromobacter; Drug Resistance, Multiple, Bacterial; Anti-Bacterial Agents; Ceftazidime; Respiratory Tract Infections; Ciprofloxacin; Microbial Sensitivity Tests
PubMed: 37971240
DOI: 10.1128/aac.00346-23 -
Cell Reports Aug 2023How the opportunistic Gram-negative pathogens of the genus Achromobacter interact with the innate immune system is poorly understood. Using three Achromobacter clinical...
How the opportunistic Gram-negative pathogens of the genus Achromobacter interact with the innate immune system is poorly understood. Using three Achromobacter clinical isolates from two species, we show that the type 3 secretion system (T3SS) is required to induce cell death in human macrophages by inflammasome-dependent pyroptosis. Macrophages deficient in the inflammasome sensors NLRC4 or NLRP3 undergo pyroptosis upon bacterial internalization, but those deficient in both NLRC4 and NLRP3 do not, suggesting either sensor mediates pyroptosis in a T3SS-dependent manner. Detailed analysis of the intracellular trafficking of one isolate indicates that the intracellular bacteria reside in a late phagolysosome. Using an intranasal mouse infection model, we observe that Achromobacter damages lung structure and causes severe illness, contingent on a functional T3SS. Together, we demonstrate that Achromobacter species can survive phagocytosis by promoting macrophage cell death and inflammation by redundant mechanisms of pyroptosis induction in a T3SS-dependent manner.
Topics: Humans; Animals; Mice; Pyroptosis; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Type III Secretion Systems; Achromobacter; Disease Models, Animal; Calcium-Binding Proteins; CARD Signaling Adaptor Proteins
PubMed: 37598340
DOI: 10.1016/j.celrep.2023.113012 -
The Journal of Infection Apr 2024
Topics: Humans; Whooping Cough; China; Pertussis Vaccine; Bordetella pertussis
PubMed: 38513738
DOI: 10.1016/j.jinf.2024.106140 -
Frontiers in Microbiology 2023Some observational studies have shown that immune thrombocytopenia (ITP) is highly associated with the alteration-composition of gut microbiota. However, the causality...
BACKGROUND
Some observational studies have shown that immune thrombocytopenia (ITP) is highly associated with the alteration-composition of gut microbiota. However, the causality of gut microbiota on ITP has not yet been determined.
METHODS
Based on accessible summary statistics of the genome-wide union, the latent connection between ITP and gut microbiota was estimated using bi-directional Mendelian randomization (MR) and multivariable MR (MVMR) analyses. Inverse variance weighted (IVW), weighted median analyses, and MR-Egger regression methods were performed to examine the causal correlation between ITP and the gut microbiota. Several sensitivity analyses verified the MR results. The strength of causal relationships was evaluated using the MR-Steiger test. MVMR analysis was undertaken to test the independent causal effect. MR analyses of reverse direction were made to exclude the potential of reverse correlations. Finally, GO enrichment analyses were carried out to explore the biological functions.
RESULTS
After FDR adjustment, two microbial taxa were identified to be causally associated with ITP ( < 0.10), namely ( = 7.31 × 10) and ( = 7.31 × 10). In addition, eight microbial taxa were considered as potentially causal features under the nominal significance ( < 0.05): , , , , , , , and . According to the reverse-direction MR study findings, the gut microbiota was not significantly affected by ITP. There was no discernible horizontal pleiotropy or instrument heterogeneity. Finally, GO enrichment analyses showed how the identified microbial taxa participate in ITP through their underlying biological mechanisms.
CONCLUSION
Several microbial taxa were discovered to be causally linked to ITP in this MR investigation. The findings improve our understanding of the gut microbiome in the risk of ITP.
PubMed: 38075905
DOI: 10.3389/fmicb.2023.1190866 -
Applied Microbiology and Biotechnology Dec 2024Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate (ODHP) was extracted in a previous study from the culture broth of soil isolate Alcaligenes faecalis MT332429...
Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate (ODHP) was extracted in a previous study from the culture broth of soil isolate Alcaligenes faecalis MT332429 and showed a promising antimycotic activity. This study was aimed to formulate ODHP loaded β-cyclodextrins (CD) nanosponge (NS) hydrogel (HG) to control skin fungal ailments since nanosponges augment the retention of tested agents in the skin. Box-Behnken design was used to produce the optimized NS formulation, where entrapment efficiency percent (EE%), polydispersity index (PDI), and particle size (PS) were assigned as dependent parameters, while the independent process parameters were polyvinyl alcohol % (w/v %), polymer-linker ratio, homogenization time, and speed. The carbopol 940 hydrogel was then created by incorporating the nanosponges. The hydrogel fit Higuchi's kinetic release model the best, according to in vitro drug release. Stability and photodegradation studies revealed that the NS-HG remained stable under tested conditions. The formulation also showed higher in vitro antifungal activity against Candida albicans compared to the control fluconazole. In vivo study showed that ODHP-NS-HG increased survival rates, wound contraction, and healing of wound gap and inhibited the inflammation process compared to the other control groups. The histopathological examinations and Masson's trichrome staining showed improved healing and higher records of collagen deposition. Moreover, the permeability of ODHP-NS-HG was higher through rats' skin by 1.5-folds compared to the control isoconazole 1%. Therefore, based on these results, NS-HG formulation is a potential carrier for enhanced and improved topical delivery of ODHP. Our study is a pioneering research on the development of a formulation for ODHP produced naturally from soil bacteria. KEY POINTS: • Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate was successfully formulated as a nanosponge hydrogel and statistically optimized. • The new formula exhibited in vitro good stability, drug release, and higher antifungal activity against C. albicans as compared to the fluconazole. • Ex vivo showed enhanced skin permeability, and in vivo analysis showed high antifungal activity as evidenced by measurement of various biochemical parameters and histopathological examination.
Topics: Rats; Animals; Hydrogels; Antifungal Agents; Fluconazole; Propionates; Alcaligenes faecalis; Candida albicans; Soil; Particle Size; Butanes
PubMed: 38217256
DOI: 10.1007/s00253-023-12819-3 -
Emerging Microbes & Infections Dec 2023is a Gram-negative, strictly human re-emerging respiratory pathogen and the causative agent of whooping cough. Similar to other Gram-negative pathogens, produces the...
is a Gram-negative, strictly human re-emerging respiratory pathogen and the causative agent of whooping cough. Similar to other Gram-negative pathogens, produces the type III secretion system, but its role in the pathogenesis of is enigmatic and yet to be elucidated. Here, we combined RNA-seq, LC-MS/MS, and co-immunoprecipitation techniques to identify and characterize the novel CesT family T3SS chaperone BP2265. We show that this chaperone specifically interacts with the secreted T3SS regulator BtrA and represents the first non-flagellar chaperone required for the secretion of an anti-sigma factor. In its absence, secretion but not production of BtrA and most T3SS substrates is severely impaired. It appears that the role of BtrA in regulating T3SS extends beyond its activity as an antagonist of the sigma factor BtrS. Predictions made by artificial intelligence system AlphaFold support the chaperone function of BP2265 towards BtrA and outline the structural basis for the interaction of BtrA with its target BtrS. We propose to rename BP2265 to BtcB for the type III chaperone of BtrA.In addition, the absence of the BtcB chaperone results in increased expression of numerous flagellar genes and several virulence genes. While increased production of flagellar proteins and intimin BipA translated into increased biofilm formation by the mutant, enhanced production of virulence factors resulted in increased cytotoxicity towards human macrophages. We hypothesize that these phenotypic traits result indirectly from impaired secretion of BtrA and altered activity of the BtrA/BtrS regulatory node.
Topics: Humans; Bordetella pertussis; Sigma Factor; Whooping Cough; Chromatography, Liquid; Artificial Intelligence; Tandem Mass Spectrometry; Bacterial Proteins; Gene Expression Regulation, Bacterial
PubMed: 37850324
DOI: 10.1080/22221751.2023.2272638