Aarti Pustam, Rajeev P Nagassar, Jayaraj Jayaraman, Adesh Ramsubhag
{"title":"Genome-resolved analysis of multidrug-resistant ESKAPE pathogens reveals Klebsiella pneumoniae diversity and plasmid-mediated resistance in a patient in intensive care.","authors":"Aarti Pustam, Rajeev P Nagassar, Jayaraj Jayaraman, Adesh Ramsubhag","doi":"10.1556/030.2026.03025","DOIUrl":"https://doi.org/10.1556/030.2026.03025","url":null,"abstract":"<p><p>Multidrug-resistant (MDR) Gram-negative pathogens continue to threaten patient outcomes in intensive care units (ICUs) worldwide, particularly in regions where genomic surveillance is limited. Understanding intra-host genomic diversity and mobility of resistance determinants remain essential for mitigating global antimicrobial resistance (AMR) threats. Whole genome sequencing and molecular analysis were performed on three selected isolates to identify resistance and virulence determinants. The isolates exhibited complex and heterogenous resistomes shaped by extensive antimicrobial exposure during prolonged ICU care. Two genetically distinct Klebsiella pneumoniae strains (ST11 and ST15) demonstrating intra-patient strain diversity, an emerging trend in high-risk clinical settings globally, along with an Acinetobacter baumannii strain (ST944) were recovered from the same patient. Key resistance genes linked to mobile genetic elements (MGEs) were identified, including blaCTX-M-15 and blaNDM-5 in K. pneumoniae ST11 and blaADC-152 in A. baumannii. A plasmid-associated contig harbouring blaDHA-1 and qnr resistance genes represented a 'high-risk' mobile platform with international similarity in K. pneumoniae, highlighting the global circulation of resistance plasmids. Virulence profiling revealed conserved and unique determinants, including biofilm, siderophore, and secretion loci, with one isolate carrying a complete Yersiniabactin locus associated with MGEs. This study provides the first genome-resolved case from the Caribbean demonstrating intra-host co-existence of globally important MDR lineages and plasmid-mediated dissemination of key resistance genes. Within the global AMR challenge, this analysis offers novel insight into the convergence of resistance and virulence traits and highlights the value of localized genomic surveillance in understanding pathogen adaptation, mobility, and persistence under high antimicrobial pressure. These findings emphasize the importance of incorporating genomic data from diverse geographic regions into global AMR networks to better manage MDR ESKAPE pathogens in ICU environments.</p>","PeriodicalId":7119,"journal":{"name":"Acta microbiologica et immunologica Hungarica","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Handayani Ali, Irene Edith Rieuwpassa, Nurlindah Hamrun, Erni Marlina, Risfah Yulianty, Fuad Husain Akbar, Dewi Ayu Siti Hartina Dewang
{"title":"Longitudinal effects of antiretroviral therapy on the oral microbiota in people living with HIV: A systematic review.","authors":"Handayani Ali, Irene Edith Rieuwpassa, Nurlindah Hamrun, Erni Marlina, Risfah Yulianty, Fuad Husain Akbar, Dewi Ayu Siti Hartina Dewang","doi":"10.1556/030.2026.02910","DOIUrl":"https://doi.org/10.1556/030.2026.02910","url":null,"abstract":"<p><p>People living with HIV frequently experience oral microbial dysbiosis, contributing to oral disease burden and reduced quality of life. Although antiretroviral therapy (ART) effectively suppresses viral replication and promotes immune recovery, its longitudinal effects on the oral microbiota remain incompletely understood. This systematic review aimed to evaluate longitudinal changes in oral microbiota composition and diversity in people living with HIV before and after ART initiation. A systematic review was conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD420251164326). Electronic searches were performed in PubMed, ScienceDirect, Wiley Online Library, DOAJ, and Google Scholar for studies published between 2015 and 2024. Eligible studies included longitudinal human studies reporting pre- and post-ART oral microbiota data using 16S rRNA gene sequencing or metagenomic approaches. Methodological quality was assessed using Joanna Briggs Institute critical appraisal tools. Due to substantial heterogeneity, findings were synthesized narratively. Six longitudinal studies met the inclusion criteria. ART was associated with partial and non-uniform modulation of the oral microbiota. Changes in beta diversity and selective taxonomic shifts were commonly reported, whereas changes in alpha diversity were inconsistent. Taxonomic alterations were more evident at the genus level, while several dominant oral genera remained stable before and after ART. Evidence linking oral microbiota changes with immune recovery was limited. Longitudinal evidence indicates that ART induces selective and heterogeneous changes in the oral microbiota without consistent normalization toward a non-HIV microbial profile, underscoring the importance of integrating oral health into long-term HIV care.</p>","PeriodicalId":7119,"journal":{"name":"Acta microbiologica et immunologica Hungarica","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148282943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Despoina Spentzouri, Petros Ioannou, Andria Papazachariou, Georgios Vougiouklakis, Vasiliki Theodorakopoulou, George Vrentzos, Maria Vakonaki, Kyriaki Tryfinopoulou, Diamantis Kofteridis
{"title":"Rare case of bacteremia, liver abscess and possible infective endocarditis caused by Fusobacterium nucleatum.","authors":"Despoina Spentzouri, Petros Ioannou, Andria Papazachariou, Georgios Vougiouklakis, Vasiliki Theodorakopoulou, George Vrentzos, Maria Vakonaki, Kyriaki Tryfinopoulou, Diamantis Kofteridis","doi":"10.1556/030.2026.03014","DOIUrl":"https://doi.org/10.1556/030.2026.03014","url":null,"abstract":"<p><p>Fusobacterium nucleatum is a Gram-negative obligate anaerobic bacterium typically found as a commensal in the human oral cavity, gastrointestinal and female genital tract. While it is a common cause of endodontic infections, it is a rare cause of infective endocarditis (IE), which can lead to high morbidity if diagnosis is delayed due to the challenges of culturing anaerobic bacteria. The case of a 75-year-old male patient with a history of type 2 diabetes who presented with high fever, rigors, and hemodynamic instability is presented herein. Physical examination revealed a new systolic murmur. Initial investigations identified inflammatory syndrome and elevated liver enzymes. Further imaging via contrast-enhanced ultrasound and computed tomography confirmed two abscesses in the left lobe of the liver. Blood cultures grew F. nucleatum, and a transesophageal echocardiogram demonstrated vegetation on the aortic valve. The patient met the Modified Duke criteria for a diagnosis of infective endocarditis. It was later elicited that the patient had undergone dental interventions one month prior to admission. The patient was successfully treated with a six-week course of targeted antimicrobial therapy consisting of ceftriaxone and metronidazole, resulting in favorable clinical recovery. Fusobacterium species are rare but significant causes of invasive infections such as liver abscesses and IE. This case emphasizes that anaerobic pathogens should be suspected in patients presenting with unexplained sepsis, concomitant deep-seated abscesses, or a history of recent dental procedures. Early use of echocardiography and anaerobic blood cultures are essential for the timely diagnosis of these rare clinical entities.</p>","PeriodicalId":7119,"journal":{"name":"Acta microbiologica et immunologica Hungarica","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"New insights into Salmonella virulence: Detection of spvB and spvR genes in avian and human isolates from northeastern Algeria.","authors":"Amira Kout, Radia Boufermes, Rania Laouar, Rachid Elgroud, Bariş Binay, Douadi Khelifi, Hajira Berredjem","doi":"10.1556/030.2026.02914","DOIUrl":"https://doi.org/10.1556/030.2026.02914","url":null,"abstract":"<p><p>The emergence of highly virulent and multidrug-resistant Salmonella strains continues to pose a major global public health concern. Building on our previous investigation of 80 Salmonella isolates obtained from avian and human sources in northeastern Algeria (Annaba and Constantine) over a three-year period (2017-2019), in which their resistance profiles to 15 antimicrobial agents were assessed, the present study further explores the molecular features of virulence by targeting two additional plasmid-encoded genes, spvB and spvR. All isolates were subjected to polymerase chain reaction (PCR) amplification using gene-specific primers. The results revealed that spvB was detected in 86.25% of isolates, while spvR was identified in 73.75%, suggesting a strong association with strains capable of causing severe systemic infections. When compared with previous reports, notable geographical variations were observed, which may reflect differences in host reservoirs, ecological conditions, and selective pressures arising from antimicrobial use. The coexistence of spv virulence genes and multidrug-resistant (MDR) phenotypes in our isolates underscores the substantial risk of dissemination of highly pathogenic and resistant Salmonella strains between animals and humans. These findings highlight the need to integrate virulence gene surveillance into existing antimicrobial resistance monitoring programs to better understand and manage the zoonotic transmission dynamics of Salmonella in Algeria.</p>","PeriodicalId":7119,"journal":{"name":"Acta microbiologica et immunologica Hungarica","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148269978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muhammad Salman Khan, Muhammad Naveed Khan, Syed Muhammad Umair, Suxin Luo, Bi Huang
{"title":"Integrative analysis of the gut-liver-heart axis in coronary artery disease: From chronic metabolic dysbiosis to acute cardiogenic shock.","authors":"Muhammad Salman Khan, Muhammad Naveed Khan, Syed Muhammad Umair, Suxin Luo, Bi Huang","doi":"10.1556/030.2026.02892","DOIUrl":"https://doi.org/10.1556/030.2026.02892","url":null,"abstract":"<p><p>The complex interplay between chronic metabolic disorders and acute cardiovascular decompensation represents a critical frontier in cardiology. This integrative research program conducted at Chongqing Medical University systematically examines the gut-liver-heart axis across the cardiovascular disease spectrum through three interconnected studies. First, a case-control investigation of coronary artery disease (CAD) patients with and without nonalcoholic fatty liver disease (NAFLD) revealed distinct intestinal dysbiosis patterns characterized by increased Coprococcus and Veillonella alongside decreased Parabacteroides, Bacteroides fragilis, and Bifidobacterium longum, with these microbial alterations correlating significantly with body mass index, triglyceride levels, and hepatic transaminases. Second, a retrospective cohort study of acute myocardial infarction complicated by cardiogenic shock demonstrated that elevated admission bilirubin (HR = 1.020, P = 0.003) and alanine aminotransferase independently predicted 30-day mortality, while serum albumin exerted protective effects (HR = 0.955, P < 0.001). Third, analysis of a comprehensive clinical registry illuminated the systemic clustering of metabolic, renal, and inflammatory abnormalities that underpin both chronic cardiometabolic disease and acute cardiovascular collapse. Collectively, these findings establish a pathogenic continuum wherein chronic intestinal dysbiosis and subclinical hepatic dysfunction create a vulnerable substrate that amplifies injury during acute ischemic events. This research framework provides mechanistic insights into the gut-liver-heart axis and proposes integrated biomarker panels for risk stratification across cardiovascular disease stages.</p>","PeriodicalId":7119,"journal":{"name":"Acta microbiologica et immunologica Hungarica","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular epidemiology and prognostic impact of lower respiratory tract infections during immune checkpoint inhibitor therapy in advanced non-small cell lung cancer: A retrospective cohort study.","authors":"Ning Xu, Chao Li","doi":"10.1556/030.2026.02970","DOIUrl":"https://doi.org/10.1556/030.2026.02970","url":null,"abstract":"<p><p>Patients with advanced non-small cell lung cancer (NSCLC) are prone to lower respiratory tract infection (LRTI) during immune checkpoint inhibitor (ICI) treatment, but the pathogen spectrum and clinical impact remain unclear. This study provides comprehensive microbiological characterization of pathogen spectrum, molecular resistance mechanisms, and prognostic significance of LRTI during ICI treatment in patients with advanced NSCLC. A single-center retrospective cohort design was adopted, and 903 patients with advanced NSCLC who first received PD-1 or PD-L1 inhibitor treatment between January 1, 2019 and November 30, 2023 were included. Molecular characterization of resistant isolates was performed using PCR and sequencing for ESBL genes (blaCTX-M, blaSHV, blaTEM), carbapenemase genes (blaKPC, blaNDM, blaVIM, blaIMP, blaOXA-48, blaOXA-23), and mecA, with multilocus sequence typing (MLST) for clonality analysis. Competing risk models estimated cumulative incidence of first LRTI; time-dependent Cox models evaluated associations with overall survival (OS) and progression-free survival (PFS). Among 903 patients, 176 (19.49%) developed LRTI during ICI treatment. Among 243 infection episodes, any phenotypic resistance was identified in 31 episodes (12.76%). Of 24 available resistant isolates, molecular characterization revealed blaCTX-M-15 as the predominant ESBL determinant (87.5%), blaKPC-2 and blaNDM-1 in CRE, blaVIM-2 and blaIMP-4 in CRPA, and blaOXA-23 in CRAB. MLST identified high-risk clones: K. pneumoniae ST11 (n = 3) and ST15 (n = 2), E. coli ST131 (n = 2), Pseudomonas aeruginosa ST235 (n = 3), A. baumannii ST2 (n = 6), and MRSA ST239 (n = 2). Older age, male sex, higher ECOG score, stage IV disease, COPD, ILD, baseline corticosteroid exposure, and higher NLR were associated with increased infection risk (all P < 0.05). First LRTI was independently associated with worse OS (HR = 1.78) and PFS (HR = 1.41). Fungal infection (HR = 2.48), mixed infection (HR = 2.34), resistance-associated infection (HR = 2.61), and severe infection (HR = 2.96) indicated worst prognosis. LRTI during ICI treatment in advanced NSCLC carries substantial burden and is associated with poor prognosis. Molecular characterization reveals that resistant infections are driven by established epidemic clones (ST2 CRAB, ST11 CRKP, ST235 CRPA, ST131 ESBL-EC), highlighting the need for enhanced infection control and targeted antimicrobial strategies in this vulnerable population.</p>","PeriodicalId":7119,"journal":{"name":"Acta microbiologica et immunologica Hungarica","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abdul Ahad Mehboob, Remsha Fatima, Saadia Kanwal, Muhammad Ali, Mona Karim, Sampana Fatima
{"title":"Exploring the gut-lung axis in post-liver transplant acute lung injury: A multi-omics approach.","authors":"Abdul Ahad Mehboob, Remsha Fatima, Saadia Kanwal, Muhammad Ali, Mona Karim, Sampana Fatima","doi":"10.1556/030.2026.02911","DOIUrl":"https://doi.org/10.1556/030.2026.02911","url":null,"abstract":"<p><p>Acute lung injury (ALI) is a significant post-operative complication of liver transplant (LT), with mounting evidence suggesting a role for the gut-lung axis. However, the mechanistic link between gut microbiota dysbiosis and ALI pathogenesis in LT recipients remains poorly understood. This hybrid translational investigation integrates transcriptomic profiling (bulk and single-cell RNA-seq), immune infiltration analysis, fecal microbiota composition (16S rRNA), and predictive functional profiling in ALI vs. non-ALI (NALI) LT patients. Machine learning algorithms (LASSO, SVM-RFE, Random Forest) were used to identify key gene biomarkers. Microbiota-host gene correlations and canonical correspondence analysis (CCA) were performed to evaluate multi-omic relationships. ALI patients exhibited reduced gut microbial diversity and increased abundance of Enterococcus and Escherichia-Shigella, alongside a depletion of beneficial taxa (Faecalibacterium, Bacteroides). CXCL3, CD48, and IRAK3 were identified as robust ALI biomarkers (Area Under the Curve >0.83), validated in both serum and Bronchoalveolar Lavage Fluid. These genes correlated positively with pro-inflammatory microbes and immune cell infiltration. Functional prediction revealed enrichment in lipopolysaccharide biosynthesis, Toll-like receptor signaling, and bacterial chemotaxis. CCA confirmed that microbiota variation significantly explained host transcriptomic variance. Our study uncovers a functional gut-lung immunological axis in post-LT ALI. Gut dysbiosis modulates immune gene expression and lung inflammation, suggesting that the microbiome serves as a potential source of diagnostic biomarkers and therapeutic targets in transplant-associated lung injury.</p>","PeriodicalId":7119,"journal":{"name":"Acta microbiologica et immunologica Hungarica","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comprehensive whole-genome sequencing reveals the resistome, virulome, and mobile genetic architecture of multidrug-resistant Acinetobacter baumannii.","authors":"Kannika Parameshwari Kannan, A S Smiline Girija","doi":"10.1556/030.2026.02983","DOIUrl":"10.1556/030.2026.02983","url":null,"abstract":"<p><p>Acinetobacter baumannii is a major cause of hospital-acquired infections and has emerged as a critical multidrug-resistant (MDR) pathogen with limited therapeutic options. In this study, two MDR clinical isolates from a tertiary care hospital in Chennai, India, selected based on their strong biofilm-producing capacity, were subjected to whole-genome sequencing (WGS) to characterize their resistome, virulome, and genomic features. Both isolates exhibited resistance to β-lactams, carbapenems, aminoglycosides, fluoroquinolones, and trimethoprim-sulfamethoxazole, while remaining susceptible to tigecycline and colistin. Genomic analysis identified key carbapenemase genes blaOXA-23, blaOXA-51, and blaOXA-144 along with additional resistance determinants including blaADC-76 and blaPER-7, aminoglycoside-modifying enzymes (ant(3″)-Ia and aph(6)), tetracycline resistance genes (tet(A), tet(B), and tet(R)), macrolide resistance gene msr(E), sulfonamide resistance gene sul1, and chloramphenicol efflux gene cmlA5. Fluoroquinolone resistance was associated with mutations in the quinolone resistance determining regions, including an S81L substitution in gyrA and multiple substitutions in parC. Virulence profiling revealed biofilm-associated genes, including bap and the pgaABC operon, along with genes linked to motility and metabolic fitness. Phylogenomic analysis showed close relatedness between the isolates and reference strains, and multilocus sequence typing (MLST) assigned both isolates to sequence type ST1051, indicating a shared clonal background. The genomes also harbored diverse mobile genetic elements, prophage regions, and siderophore-associated biosynthetic gene clusters, reflecting high genomic plasticity. Overall, this study highlights the coexistence of multiple resistance and virulence determinants in biofilm-forming MDR A. baumannii, emphasizing the importance of genome-based surveillance for monitoring high-risk strains in clinical settings.</p>","PeriodicalId":7119,"journal":{"name":"Acta microbiologica et immunologica Hungarica","volume":" ","pages":"168-181"},"PeriodicalIF":1.5,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148025778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gut microbiota: The hidden hallmark of aging.","authors":"Kimaya Kaushik, Mihir Sharma, Ritik Sharma, Asif Reza, Geetansh Sharma, Saetukrit Panwar, Rupak Nagraik, Poonam Negi, Avinash Sharma","doi":"10.1556/030.2026.02808","DOIUrl":"https://doi.org/10.1556/030.2026.02808","url":null,"abstract":"<p><p>Aging is the natural process of changes that are accumulated over time and are responsible for the ever-increasing susceptibility to diseases and death. Extensive research has been done to understand the role of gut microbiota in aging, however, limited progress has been made. Thus, considering the need of the hour we have tried to give a new perspective to this body of research by delving deep into all major factors that are associated with gut microbiome and aging. This review presents a holistic view of the relation between gut microbiome and aging starting from hallmarks of aging and evolution of gut microbiome over lifespan to intricate mechanisms like inflammaging, immunosenescence, gut-brain axis, mitochondrial dysfunction, nutrient imbalance and cardiac implications. In addition, it highlights different therapies like fecal microbiota transplantation, omics and metabolomics studies, and gut modulation therapies that show a promising future towards regulation of gut microbiota for aging interventions. More importantly, this review is an addition to the existing literature which advocates gut microbiome as an additional hallmark of aging, summarising the known status of the research in this field, contributing to developing gut microbiota targeted healthy aging.</p>","PeriodicalId":7119,"journal":{"name":"Acta microbiologica et immunologica Hungarica","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association of baseline lower respiratory tract microbiota composition and bacterial load with the risk of PD-1/PD-L1 inhibitor-associated immune-related pneumonitis: A single-center prospective cohort study.","authors":"Yun Wang, Xuefeng Wang, Henggen Zhou","doi":"10.1556/030.2026.02909","DOIUrl":"https://doi.org/10.1556/030.2026.02909","url":null,"abstract":"<p><p>Immune checkpoint inhibitors improve outcomes in solid tumors, but immune-related pneumonitis (irP) can lead to treatment interruption and even death; current stratification mainly relies on medical history and imaging, lacking reproducible organ-specific biomarkers. This prospective cohort study evaluated the association of baseline lower respiratory tract microbiota features and bacterial load with the risk of PD-1/PD-L1-related irP. Bronchoalveolar lavage was performed before immunotherapy; 16S sequencing derived the Pathogen-Enrichment Score (PES), and quantitative PCR quantified total bacterial load. The primary endpoint was first occurrence of grade ≥2 irP within 6 months. Firth-corrected multivariable logistic regression adjusted for prior thoracic radiotherapy, baseline interstitial lung disease, and recent antibiotic use. Of 294 evaluable cases, 34 developed grades ≥2 irP. Baseline total bacterial load was significantly higher in patients who later developed irP, showing a monotonic dose-response relationship with risk (nonlinearity P = 0.183); adjusted odds ratio = 1.58 per 1 log10 copies/mL (P = 0.024). PES was also elevated (adjusted odds ratio = 1.43 per 1 SD, P = 0.033). The dysbiotic phenotype was characterized by reduced diversity and enrichment of Streptococcus, Veillonella, and Haemophilus, genera commonly associated with oral microbiota and aspiration. Adding PES and bacterial load to a clinical model improved discrimination (AUC 0.81 vs 0.73, P = 0.019) and reclassification (categorical NRI = 0.24, P = 0.004). Event rates across risk strata were 2.24, 13.46, and 32.65%. Baseline lower respiratory tract dysbiosis and elevated bacterial load indicate higher irP risk; adding these microbiologic measures to a clinical model improves prediction and risk stratification.</p>","PeriodicalId":7119,"journal":{"name":"Acta microbiologica et immunologica Hungarica","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}