Frontiers in Cellular and Infection Microbiology最新文献

Peri-implantitis is an inflammatory disease affecting tissues surrounding dental implants, with microbial biofilms recognized as the primary etiological factor. However, most previous studies analyzed samples from peri-implant pockets, and research on biofilms directly attached to explanted implant surfaces remains limited. This study compared the microbial composition and functional characteristics of biofilms from explanted implant surfaces in peri-implantitis cases with subgingival plaque from healthy controls. A total of 41 samples (peri-implantitis n=19, healthy controls n=22) were obtained from the Apple Tree Oral Biobank. The V3-V4 region of 16S rRNA gene was sequenced using Illumina MiSeq, ASVs were generated using DADA2, and taxonomic assignment was performed using SILVA database (v138.1). Alpha and beta diversity analyses were conducted, and functional potential was predicted using PICRUSt2. The peri-implantitis group showed significantly higher Simpson index (p=0.0086) and phylogenetic diversity (p<0.0001), with distinct clustering separation between groups. Beyond well-known periodontal pathogens (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Filifactor alocis), the peri-implantitis group exhibited significant increases in sulfate-reducing bacteria (Desulfobulbus, Desulfovibrio) and emerging pathogens ([Eubacterium] nodatum group, [Eubacterium] saphenum group, Phocaeicola abscessus, Pseudoramibacter alactolyticus, Pyramidobacter). Health-associated bacteria (Corynebacterium, Neisseria, Capnocytophaga, Lautropia) were decreased. Functional analysis revealed enrichment in LPS biosynthesis, sulfur metabolism, iron acquisition, and amino acid degradation pathways, while carbohydrate metabolism was decreased. This study demonstrates that diverse emerging pathogens, including sulfate-reducing bacteria, are associated with peri-implantitis biofilms in explanted implant surface biofilms, contributing to expanded understanding of peri-implantitis etiology and development of candidate biomarkers.

Background: Sepsis-induced acute lung injury (SI-ALI) is associated with high mortality. The gut microbiota-bile acid axis plays a critical role in regulating host inflammatory responses; however, the mechanism of action of traditional Chinese medicine (TCM) compounds targeting this axis remains unclear.

Aim: This study aimed to systematically evaluate the protective effects of Modified DaChengqi Decoction (MDD) against lipopolysaccharide (LPS)-induced SI-ALI and to elucidate its underlying mechanism in modulating inflammation and neutrophil extracellular traps (NETs) through the regulation of gut microbiota and bile acid metabolism.

Methods: An LPS-induced mouse model of SI-ALI was established. Mice were orally administered MDD, and 72-h survival rate, lung function, histopathology, and inflammatory cytokine levels were assessed. Fecal 16S rRNA sequencing and targeted bile acid metabolomics were combined to analyze changes in the microbiota and metabolites. Network pharmacology was employed to screen key targets, followed by experimental validation using Western blotting, immunohistochemistry, and ELISA to confirm candidate pathways.

Results: Compared with the model group, MDD significantly improved survival and lung function, alleviated pulmonary inflammation and vascular permeability. Microbiomic analysis revealed that MDD downregulated the abundance of Parabacteroides and Bacteroides. Targeted metabolomics showed that MDD markedly altered the levels of several primary and secondary bile acids, mainly including glycoursodeoxycholic acid (GUDCA), taurochenodesoxycholic acid (TCDCA), chenodeoxycholic acid (CDCA), and taurocholic acid (TCA). Molecular validation demonstrated that the nuclear receptor FXR was significantly upregulated, while the TLR4 and downstream MYD88-NF-κB/JNK signaling pathways were inhibited. Additionally, the expression of PAD4 and CitH3 as well as NETs formation were reduced.

Conclusion: MDD can alleviate LPS-induced SI-ALI by modulating the gut microbiota-bile acid metabolism, activating FXR, and thereby suppressing the TLR4/MYD88-mediated inflammatory cascade and NETs generation.

Objective: To evaluate the diagnostic performance and clinical utility of metagenomic next-generation sequencing (mNGS) in distinguishing immune checkpoint inhibitor-related pneumonitis (CIP) from infectious pneumonia in cancer patients undergoing immunotherapy.

Methods: A retrospective tertiary hospital cohort included 34 cancer patients (Feb 2022-Jan 2024) with prior ICI exposure, new/worsening respiratory symptoms, imaging infiltrates, and both mNGS and conventional microbiological testing (CMT). Final diagnoses were adjudicated by a multidisciplinary panel. We compared pathogen detection rates, sensitivity, specificity, and turnaround times (TAT) between mNGS and CMT.

Results: In the infectious pneumonia group, mNGS detected pathogens in 17/18 cases (94%), whereas CMT detected only 6/18 (33%). In the CIP group, mNGS was negative in 14/16 cases (88%), compared with 11/16 negatives by CMT (69%). Using the adjudicated diagnosis as the reference, mNGS showed sensitivity 88%, and specificity 94%. In contrast, CMT's sensitivity was 69%, and specificity 33%. The median TAT for mNGS was 24 hours (IQR 22-31 h), versus 121.5 hours (IQR 80.5-156 h) for CMT (P < 0.001).

Conclusion: mNGS outperforms CMT in both diagnostic accuracy and timeliness for distinguishing CIP from infectious pneumonia among immunotherapy recipients. Incorporation of mNGS into the diagnostic workflow for suspected CIP may improve etiological discrimination and enable timely, individualized treatment. Further large-scale prospective studies are required to confirm these findings.

Background: The diagnosis of active tuberculosis (ATB) in children and adolescents is limited by non-specific symptoms, paucibacillary infection, and the low sensitivity of traditional tools. These limitations can lead to delayed treatment and increased complications.

Methods: This retrospective study recruited 1,080 participants. We performed receiver operating characteristic (ROC) curves to evaluate the diagnostic performance of logarithmic neutrophil-to-lymphocyte ratio (logNLR) for ATB infection. We employed logistic regression, restricted cubic spline (RCS), stratified, and interaction analyses to evaluate the association between logNLR and ATB infection.

Results: The logNLR was significantly associated with ATB infection in the adjusted model (OR = 1.38, 95% CI: 1.01-1.88, P = 0.044). The RCS curve indicated a non-linear relationship between logNLR and ATB infection, with the critical threshold of 0.9232. The breakpoint analyses further confirmed that when logNLR<1.379, the indicator logNLR was positively correlated with ATB infection. Stratified analyses showed logNLR was a reliable predictor in males, 0-7 and 15-17 years old, those with Mycobacterium tuberculosis (MTB) exposure, and participants with CD4+ T cell counts>414 cells/μL or CD8+ T cell counts>238 cells/μL (all P<0.05). Interaction analyses revealed that children with both CD4+ T cell counts ≤414 cells/μL and MTB exposure had a substantially higher ATB risk (OR = 19.31). Similarly, synergies were observed in combinations of CD4+ T cell counts ≤414 cells/μL with 0-14 years old, and MTB exposure with 0-14 years old.

Conclusions: The logNLR is a simple, low-cost, and effective biomarker for diagnosis of ATB in children and adolescents. The critical threshold and breakpoint of logNLR enable precise risk stratification, providing valuable support for early ATB identification in this population.

Background: Glaesserella parasuis (G. parasuis), is a key respiratory pathogen responsible for Glässer's disease in pigs, characterized by polyserositis, arthritis, and pulmonary lesions. While it disrupts the respiratory microbiota, its impact on the gut-lung axis, a critical pathway for systemic immune and metabolic crosstalk, remains unexplored.

Methods: We established a piglet infection model using the highly virulent G. parasuis strain XX0306 (serotype 5). Systemic effects were investigated through integrated 16S rDNA sequencing of the lung and gut microbiota, complemented by untargeted metabolomics of intestinal contents. We performed histopathological examination and measured serum biomarkers (diamine oxidase and D-lactate) to assess intestinal barrier integrity. Correlation analysis linked microbial shifts to host metabolic alterations.

Results: Infection induced profound dysbiosis in both the lung and gut microbiota. Pulmonary microbial diversity and functional potential declined. Gut dysbiosis featured a loss of beneficial bacteria and enrichment of potential pathogens (e.g., Streptococcus, Campylobacter, Desulfovibrio). Functional prediction indicated significant alterations in 12 gut microbial metabolic pathways, with downregulated amino acid metabolism and upregulated carbohydrate/lipid metabolism and xenobiotic degradation. Metabolomics identified 30 differentially abundant metabolites (e.g., argininosuccinate, liquiritigenin, citrulline), primarily enriched in cytochrome P450-mediated xenobiotic metabolism and arginine biosynthesis. Argininosuccinate levels correlated with pathogenic genera (Leucobacter, Streptococcus, Desulfovibrio). Infected piglets exhibited significant intestinal barrier damage, evidenced by elevated serum diamine oxidase (DAO) and D-lactate (D-LA).

Conclusion: This study demonstrates that G. parasuis infection extensively remodels the gut-lung axis microbiota and host metabolome, leading to intestinal barrier impairment. The perturbation of arginine biosynthesis may compromise host immunity. These results provide novel mechanistic insights into the pathogenesis of Glässer's disease.

Zika virus (ZIKV) causes severe neurological disease, including microcephaly and Guillain-Barré syndrome, through complex interactions with host cell proteins. This review synthesizes the 2015-2025 published literature on ZIKV-host protein interactions and their therapeutic targeting. ZIKV enters cells via multiple receptor pathways: adhesion receptors (DC-SIGN, Hsp70), high-affinity entry receptors (ITGB4, GRP78, NCAM1), internalization receptors (integrin αvβ5, sialic acid), and endosomal receptors (AXL, TIM-1, CD300a). Viral structural proteins direct virion assembly, while nonstructural proteins NS1-NS5 suppress immune responses, remodel cellular membranes, and dysregulate gene expression. NS5 uniquely suppresses neurodevelopmental genes and disrupts ciliary function through nuclear localization, directly driving microcephaly pathogenesis. Therapeutic strategies include receptor antagonists, protease inhibitors, and polymerase inhibitors. However, receptor redundancy, viral protein multifunctionality, and pregnancy safety constraints limit clinical translation. This review identifies ZIKV-host protein interactions as therapeutic targets and highlights barriers to drug development.

Introduction: BK polyomavirus (BKPyV) is a ubiquitous human pathogen that typically causes nephropathy and hemorrhagic cystitis in immunocompromised patients. Although BKPyV shares close genetic and structural similarity with JC polyomavirus (JCPyV), which is responsible for progressive multifocal leukoencephalopathy (PML), its neurotropic potential remains poorly characterized. Rare reports have suggested possible central nervous system (CNS) involvement under conditions of severe immune suppression. Here, we describe the first documented case of BKPyV-associated PML in a patient with erythrodermic mycosis fungoides treated with Mogamulizumab, a CCR4-targeting monoclonal antibody that profoundly alters immune surveillance.

Results: We describe a patient with erythrodermic mycosis fungoides and long-standing immunological frailty, who developed neurological symptoms during Mogamulizumab therapy. Brain MRI showed multifocal white matter lesions compatible with PML. BKPyV DNA was detected in plasma, urine, and cerebrospinal fluid (CSF), while JCPyV DNA was absent. Serological testing showed high anti-BKPyV and anti-JCPyV IgG levels in plasma, indicating prior exposure to both viruses, while antibodies were undetectable in CSF, consistent with lack of intrathecal synthesis. This compartmental dissociation between plasma and CSF, together with the detection of BKPyV DNA and the absence of JCPyV DNA in CSF, supports BKPyV as the etiological neurotropic agent responsible for leukoencephalopathy. Sequencing of the VP1 and NCCR regions revealed compartment-specific nucleotide and amino acid variants, including non-conservative substitutions in the CSF isolate, suggesting intra-host viral heterogeneity. Compartment-specific sequence variability of viral protein 1 (VP1) and structural rearrangements of the non-coding control region (NCCR), particularly the loss of the Q and R block in CSF-derived isolates, underscore intra-host heterogeneity of BKV and may contribute to its adaptation and neurotropic potential.

Conclusion: This is the first documented case of BKPyV-associated PML in a Mogamulizumab-treated patient. These findings highlight intra-host heterogeneity at the protein level, possibly reflecting compartment-specific viral evolution, and underscore the need for vigilant BKPyV and JCPyV monitoring during Mogamulizumab treatment.

The emergence and development of bone tumors stem from a combination of intrinsic genetic alterations in tumor cells, remodeling of the bone marrow microenvironment, and shifts in the host's systemic immune-metabolic state. In recent years, gut microorganisms have been shown not only to influence bone mass regulation and conditions involving disrupted bone homeostasis, such as osteoporosis, but also to substantially affect the formation of primary bone tumors and metastatic lesions by modulating immune cell differentiation, inflammatory activity, and the coupling of bone remodeling. Focusing on the "Microbiota-Immune-Bone axis" (MIB), a growing body of fundamental and translational research indicates that alterations in gut microbial composition and function can reshape metabolite profiles-including short-chain fatty acids, bile acids, indole derivatives-and pathogen-associated molecular patterns (PAMPs). These signals act on the intestinal barrier and bone marrow immunity through G-protein-coupled receptors, nuclear receptors, and pattern-recognition receptors, thereby shifting the balance between bone resorption and formation and modifying the immune characteristics of the bone microenvironment, ultimately facilitating bone tumor cell colonization, proliferation, and immune escape. This review takes the MIB axis as its central framework to integrate the major pathways through which gut microbes and their metabolites regulate intestinal and myeloid immunity, bone remodeling, and bone tumor biology, to construct a systems-level model of tumor initiation and progression, to identify druggable signaling nodes, and to assess the potential and challenges of microbiota-modulating approaches-including antibiotics, probiotics, dietary strategies, and fecal microbiota transplantation-in preventing and treating bone tumors, thereby offering a theoretical foundation for developing integrated interventions targeting the gut microbiota and the MIB axis.

Introduction: Toxoplasma gondii is an obligate intracellular parasite with an exceptional capacity to colonize a broad range of host species and cell types. Successful infection depends on its ability to manipulate host metabolism, including lipid pathways that are essential for membrane biogenesis, signalling, and immune modulation. Extracellular vesicles (EVs) are increasingly recognized as critical mediators of parasite-host interactions, but while their protein and nucleic acid cargo has been studied, the lipid composition of T. gondii EVs (TgEVs) remains poorly defined.

Methods: In this study, we performed a lipidomic analysis of TgEVs secreted by tachyzoites grown in four distinct host cell types: fibroblasts, Vero cells, myoblasts, and porcine intestinal epithelial cells (IPEC). Cells and TgEVs were isolated from five biological replicates per condition and analysed by liquid chromatography coupled to high-resolution tandem mass spectrometry. Comparative lipid profiling of TgEVs and their corresponding host cells was performed after total ion current normalization, followed by principal component analysis to capture global compositional patterns and pairwise differential abundance testing to identify significantly enriched or depleted lipid species.

Results: We identified 194 lipid species across 15 classes. Despite metabolic differences among host cell types, TgEVs displayed a highly conserved and distinctive lipid profile. Glycerophospholipids such as phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were the most abundant components, while sphingolipids, including sphingomyelin and ceramides, were consistently present and likely contribute to vesicle biogenesis and cargo organization. Notably, triacylglycerols (TG) were enriched in TgEVs across all host conditions, suggesting active selection of neutral lipids during vesicle formation. Correlation analyses confirmed that TgEV lipidomes diverge from their cellular origin, indicating a process of active sorting rather than passive acquisition from the host membrane.

Discussion: These findings indicate that T. gondii produces vesicles with conserved and distinctive lipid compositions that differ from those of the host cell. This selective lipid core hints at key functions in parasite, host communication, immune modulation, nutrient acquisition, and other vesicle-cell interactions. Our work advances the molecular understanding of TgEVs and establishes a foundation for future studies into how lipid-mediated signalling contributes to the complex dynamics of T. gondii infections in different cellular environments.