Lung cancer is the most common cancer type and the most common cause of cancer-related deaths worldwide. Recently, the lung microbiome has garnered significant attention as a novel therapeutic target for lung cancer. Next-generation sequencing technologies have revealed the existence of a lung microbiome, suggesting a close association between lung microorganisms and the development of lung cancer. This interaction is mediated through various pathways, including immune modulation, alteration of cellular niches and drug metabolism, which ultimately affects lung cancer progression. This review synthesizes pioneering advances from the past two decades that redefine the lung microbiome as a functional mediator, rather than a passive marker, of lung cancer pathogenesis, with mechanistic insights rigorously derived from integrated in vitro and in vivo studies. Through coculture models and animal experiments, key microbial shifts, such as enrichment of Streptococcus and Veillonella and depletion of Neisseria, have been found to contribute to cancer progression via activation of immune pathways (eg, TLR2 and γδ T cells) and sustained proinflammatory signaling. Clinically, microbial biomarkers (eg, Capnocytophaga and HPV) and microbiota-targeted therapies (eg, nebulized antibiotics and IL-17A blockade) show promise for diagnosis and treatment. These insights underscore the potential of the lung microbiome as a source of biomarkers and therapeutic targets, urging future research to elucidate mechanisms, validate findings in larger cohorts and translate discoveries into personalized strategies for early detection and improved outcomes.

Mpox virus (MPXV) is the only pathogen that triggered two Public Health Emergency of International Concern (PHEIC) declarations, first in July 2022 and then again in August 2024. The 2022 outbreak was attributed primarily to clade IIb MPXV, specifically lineage B.1. However, the 2024 global outbreak was largely due to the emergence of clade Ib MPXV, which was first identified in the Sud Kivu region of the Democratic Republic of the Congo in 2023. During this period, the transmission route of MPXV transitioned from primarily zoonotic spillovers to sustained human-to-human transmission, disproportionately affecting vulnerable groups such as men-who-have-sex-with-men, immunocompromised individuals and marginalized populations with limited access to healthcare. This shift has been driven by critical mutations in genes associated with viral fitness, immune evasion, and transmission dynamics. Moreover, these changes correspond with atypical and often milder yet more transmissible clinical presentations, complicating the detection and management of cases. Despite these challenges, health system preparedness has remained uneven. High-income countries leverage existing infrastructure to facilitate rapid responses through proactive policies and financial commitments. However, many low- and middle-income countries struggle with delayed case detection, limited surge capacity, community unawareness and fragmented outbreak governance. Although diagnostics, vaccines and antivirals have advanced, issues such as accessibility, affordability and distribution have persisted, hindering global solidarity efforts. This narrative review integrates evidence on the evolution of MPXV clades, clinical heterogeneity and public health responses. Furthermore, by learning from past outbreaks, this review proposes actionable, time-sensitive recommendations to strengthen surveillance, ensure equitable deployment of countermeasures, secure supply chains, and embed One Health approaches for increased resilience.

Rheumatoid arthritis (RA) is associated with alterations in the gut bacterial composition, but the contribution of the viral community (virome) to disease pathogenesis remains poorly understood. Here, we employed metagenomic sequencing to perform a stratified comparative analysis of gut virome profiles across three clinically defined cohorts: healthy controls and patients with mild or severe RA. We constructed a tripartite interaction network that integrates viral operational taxonomic units, bacterial taxa with RA-pathogenic potential, and disease-specific clinical parameters to delineate the mechanistic interplay between virome perturbations and RA progression. Metavirome profiling revealed significant shifts in gut viral diversity among RA patients, including an increased abundance of Peploviricota and a marked depletion of Podoviridae phages. Concurrently, bacteriome analysis revealed that Blautia, Bifidobacterium and Anaerobutyricum were enriched in the gut microbiota of RA patients, whereas Phocaeicola and Bacteroides were markedly depleted. These microbial alterations were significantly correlated with elevated levels of proinflammatory cytokines, Th17/Treg imbalance and clinical scores. Further analysis revealed enhanced viral-bacterial cross-boundary interactions, such as the co-enrichment of Acinetobacter phage with Blautia, which may exacerbate inflammation through lipopolysaccharide release. Together, our findings highlight the critical role of synergistic dysregulation between the gut virome and bacteriome in RA pathology. Longitudinal studies are warranted to establish causal relationships and explore the therapeutic potential of phage therapy or probiotic modulation.

Abstract This study explores the potential of using the gut microbiota as a biomarker for liver disease classification by constructing machine learning classifiers. The classifiers were designed based on the abundance of 10 dominant bacterial taxa to categorize different liver disease scoring systems, including Child-Pugh score, model for end-stage liver disease (MELD), albumin-bilirubin (ALBI), fibrosis 4 score (FIB-4) and aspartate aminotransferase-to-platelet ratio index (APRI). Significant variations in gut microbiota composition were observed across various stages of liver disease. For example, the relative abundances of Enterococcus, Lactobacillus and Eubacterium rectale exhibited notable differences between cirrhotic patients with Child–Pugh grades A and B and grades A and C, and between patients with MELD scores of 6–15 and those with MELD scores of 15–40. In terms of the FIB-4 index, Enterococcus, Lactobacillus, Clostridium leptum, E. rectale and Faecalibacterium prausnitzii differed significantly across the low-, medium- and high-fibrosis groups. Analysis of the ALBI score revealed significant differences in the abundances of Enterococcus, Lactobacillus, Bacteroides, C. leptum, E. rectale and F. prausnitzii between grade 1 and grades 2–3. We constructed classifiers using machine learning algorithms based on the content of 10 dominant gut bacteria to classify the grading of different scoring systems. The highest area under the receiver operating characteristic (AUROC) values reported were for CP_XGBoost (0.7090 for Child–Pugh), MELD_SVM_UP (0.6346 for MELD), ALBI_XGBoost_SMOTE (0.7298 for ALBI), FIB4_SVM_UP (0.5873 for FIB-4) and APRI_SVM_UP (0.6826 for APRI). These findings highlight the potential of integrating gut microbiota analysis into existing liver disease scoring frameworks to increase diagnostic accuracy and improve patient care.

Abstract Helicobacter pylori infection, affecting over 4.4 billion individuals globally, is a leading cause of chronic gastritis, peptic ulcers and gastric cancer. At present, the standard therapeutic approach for H. pylori infection continues to rely on high-dose antibiotic regimens, despite growing concerns about antibiotic resistance and treatment-associated dysbiosis. Probiotics, particularly Lactobacillus species, have emerged as promising adjuncts due to their multifaceted anti-H. pylori mechanisms. However, only a limited number of existing strains have demonstrated efficacy in treating H. pylori infections. This study investigated the effects of Lactiplantibacillus plantarum HCS03-001 (LP-HCS03) and Lacticaseibacillus paracasei HCS17-040 (LPC-HCS17) against H. pylori using a mouse model. In infected mice, administration of the combined probiotics with 1 × 109 CFU each significantly decreased mRNA expression levels of ureA/ureB (P < 0.001), increased the level of IL-10, and decreased the levels of IL-17 and TNF-α (P < 0.001), which indicates that the intervention reduced gastric colonization, alleviated inflammation and promoted the restoration of the gastric mucosal barrier. The microbiota in both the stomach and intestines were reconstructed, with particularly pronounced effects observed in the stomach. These findings highlight LP-HCS03 and LPC-HCS17 as promising probiotics to augment H. pylori eradication while preserving microbial homeostasis.

Abstract Community-acquired pneumonia (CAP) is a common respiratory tract infection in children that is caused by various pathogens, including bacteria, Mycoplasma pneumoniae (MP), respiratory syncytial virus (RSV), and SARS-CoV-2, which was the most widespread causative pathogen in recent years. We compared pathogen-specific CAP to identify shared and distinct host responses. This single-center, retrospective cohort study enrolled 200 children hospitalized for CAP caused by SARS-CoV-2, MP, RSV and bacterial infections from January 2019 to February 2023. We included only patients with mild symptoms and performed propensity score matching to adjust for age and sex. Patients with CAP due to COVID-19 were more prone to fever and poor appetite (P < 0.01) but had a lower incidence of cough and moist and wheezing rales (P < 0.01) and a shorter disease course (P < 0.01). The frequencies of antibiotic, anti-inflammatory drug and oxygen therapy use were lower in the CAP-COVID-19 group than in the non-COVID-19 CAP groups (P < 0.01). Additionally, white blood cell, lymphocyte and eosinophil counts were lower in the CAP-COVID-19 group than in the non-COVID-19 CAP groups (P < 0.01). However, the procalcitonin levels in the CAP-COVID-19 group were higher than those in the CAP-bacteria (P < 0.05) and CAP-MP groups (P < 0.01). Moreover, we observed significant differences in nutritional status (total protein and albumin), renal function (serum creatinine and urea) and myocardial function (creatine kinase and creatine kinase-MB) between the CAP-COVID-19 and CAP-MP groups. Our results revealed shared and distinct pathophysiological features across pathogen-specific CAP, enabling precise diagnosis and treatment.

The global spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) severely threatens public health, with its resistance profile highly dependent on carbapenemase subtypes, such as Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), and oxacillinase (OXA)-48. However, existing detection technologies have limitations such as insufficient sensitivity, high cost or complex operation. This study combines matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with convolutional neural networks (CNNs) to establish a rapid and precise system for identifying carbapenemase subtypes in CRKP. An end-to-end CNN classification model was constructed by performing high-resolution mass spectrometry analysis on 205 clinical CRKP isolates (including 111 KPC–, 47 NDM– and 47 OXA-48–producing isolates), with 12 technical replicates per strain. The model employs a hierarchical convolutional architecture to automatically analyze full-spectrum domain features, achieving an overall accuracy of 96.1% in five-fold cross-validation, with a KPC subtype identification rate of 98.88%. Compared with traditional machine learning methods, such as random forest, support vector machine and AdaBoost, CNN demonstrated superior parameter efficiency and subtype discrimination capability under limited sample sizes. The technical process can be completed within 20 minutes after bacterial culture at a significantly lower cost than that of molecular detection. The modular design of the model supports the rapid integration of region-specific strain databases, providing a scalable solution to address the regional heterogeneity of carbapenemase distribution. This study confirms the translational potential of artificial intelligence–enhanced mass spectrometry technology in enzyme-targeting precision therapy and antibiotic resistance control, providing clinical microbiology laboratories with an alternative tool that offers timeliness, cost-effectiveness and diagnostic accuracy.

Bacteria often possess elaborate riboflavin provision pathways with puzzling roles in physiology. Vibrio cholerae has a riboflavin biosynthetic pathway (RBP) with putative genetic redundancy. Particularly, this species contains a putative ribBX (originally annotated as ribBA) fusion gene on its main RBP operon in addition to monocistronic ribB and ribA genes. In this study, sequence analysis and heterologous complementation experiments were performed to evaluate the functions of RibBX, RibB and RibA of the RBP of V. cholerae. The results indicate that the RibB dihydroxy-butanone phosphate synthase function is provided by both the RibBX hybrid and the orphan RibB. RibBX homologs have been described in other members of the proteobacteria. These proteins conserve RibB activity, but the exact function of the RibX domain remains unelucidated. Here, structural comparisons of the RibB and RibX domains of RibBX homologs in proteobacteria evidenced structural variation in the RibX domain across bacteria, suggesting differential functions. Moreover, this analysis identified the carriage of one extra domain putatively involved in genetic regulation in a group of orthologs within the Neisseriaceae family. Together, the results show that in V. cholerae, RibB activity is provided by the presence of monofunctional RibB and a RibBX hybrid. Notably, the function of the RibX domains fused to RibB may vary across bacteria and some hybrids include yet extra functional domains.