A systematic framework for understanding the microbiome in human health and disease: from basic principles to clinical translation

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 23, 2024

Language: Английский

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Gut–liver translocation of pathogen Klebsiella pneumoniae promotes hepatocellular carcinoma in mice

Nature Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Language: Английский

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Neutrophil recruitment during intestinal inflammation primes Salmonella elimination by commensal E. coli in a context-dependent manner

Cell Host & Microbe, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Foodborne bacterial diarrhea involves complex pathogen-microbiota-host interactions. Pathogen-displacing probiotics are increasingly popular, but heterogeneous patient outcomes highlighted the need to understand individualized host-probiotic activity. Using mouse gut commensal Escherichia coli 8178 and human probiotic E. Nissle 1917, we found that degree of protection against enteric pathogen Salmonella enterica serovar Typhimurium (S. Tm) varies across mice with distinct microbiotas. Pathogen clearance is linked enteropathy severity subsequent recruitment intraluminal neutrophils, which differs in a microbiota-dependent manner. By combining knockout antibody-mediated depletion models genetics, show neutrophils host-derived reactive oxygen species directly influence coli-mediated S. Tm displacement by potentiating siderophore-bound toxin killing. Our work demonstrates how host immune factors shape pathogen-displacing efficiency while also revealing an unconventional antagonistic interaction where synergize displace pathogen.

Language: Английский

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Colonization resistance: the role of gut microbiota in preventing Salmonella invasion and infection

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: Nov. 8, 2024

The human gastrointestinal tract is colonized by a complex microbial ecosystem, the gut microbiota, which pivotal in maintaining host health and mediating resistance to diseases. This review delineates colonization (CR), critical defensive mechanism employed microbiota safeguard against pathogenic bacterial invasions, notably

Language: Английский

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Klebsiella oxytoca facilitates microbiome recovery via antibiotic degradation and restores colonization resistance in a diet-dependent manner

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 9, 2025

Abstract Competition among bacteria for carbohydrates is pivotal colonization resistance (CR). However, the impact of Western-style diets on CR remains unclear. Here we show how competition between Klebsiella oxytoca and pneumoniae modulated by consuming one three characterized high-starch, high-sucrose, or high-fat/high-sucrose content. In vivo experiments in ampicillin-treated mice reveal that K. promotes decolonization all dietary backgrounds. diet reduced pathogen clearance. Microbiome analysis reveals combination ampicillin treatment synergize microbiome impairment, particularly noticeable presence high fat The diet-independent degradation gut lumen beta-lactamases facilitates rapid commensal outgrowth, which required subsequent Our findings provide insights into modulates functional recovery -mediated elimination from gut.

Language: Английский

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The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in Klebsiella oxytoca

Microorganisms, Journal Year: 2025, Volume and Issue: 13(1), P. 158 - 158

Published: Jan. 14, 2025

Klebsiella oxytoca toxigenic strains represent a critical health threat, mainly due to their link antibiotic-associated hemorrhagic colitis. This serious condition results from the bacteria’s ability produce tilimycin and tilivalline cytotoxins. Our research highlights pivotal role of OmpR, key regulator within EnvZ/OmpR two-component system, in controlling virulence factors associated with K. oxytoca. findings strongly indicate that OmpR is repressor aroX npsA genes, first genes NRPS operons, respectively, which are indispensable for producing these enterotoxins. Notably, absence we observe significant increase cytotoxic effects on Caco-2 cells. These observations identify as crucial negative transcription both effectively managing release deepens our understanding mechanisms opens promising avenues targeting new therapeutic interventions. By focusing this innovative approach, can develop more effective solutions combat pressing challenge, ultimately improving patient outcomes against pathogen.

Language: Английский

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Strain-specific galactose utilization by commensalE. colimitigatesSalmonellaestablishment in the gut

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Abstract Salmonella enterica serovar Typhimurium ( S . Tm) is a major cause of gastrointestinal diseases worldwide. To date, options for prevention or curative therapy remain limited. The gut microbiota plays protective role against enteric diseases, particularly in preventing establishment and proliferation Tm. While most research has focused on microbiota-mediated pathogen exclusion during the later, inflammation-dominated stages infection, little known about how members mitigate Tm early colonization. address this gap, we conducted 24 h vivo competitive experiments using different commensal E. coli strains. We observed significant reduction load, which was strain-specific evident with 8178. investigate underlying molecular mechanisms, performed an screen rationally designed library -which includes wide range carbohydrate utilization mutants - both absence presence Our findings revealed that 8178-mediated competition driven by exploitation galactose stage infection. Identifying as key metabolite enhances our mechanistic understanding protection opens new avenues developing microbiota- dietary-based strategies to better control intestinal infections.

Language: Английский

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Unraveling the genomic epidemiology and plasmid-mediated carbapenem resistance of Klebsiella pasteurii

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: March 17, 2025

This study isolated a Klebsiella pasteurii strain, K1134, from the sputum of an ICU patient, revealing its resistance to carbapenem antibiotics meropenem and imipenem. Whole-genome sequencing identified plasmid pK1134-KPC, which carries gene bla KPC-2. belonging IncFIIpCP020359 group, exhibits modular structure with KPC-2 embedded in 32.09 kb accessory region containing multiple genetic elements (AGEs). Comparative genomic analysis 48 K. isolates 12 countries showed high diversity, strains clustered into three clades. Notably, harbors extensive antimicrobial genes across diverse AGEs, classifying it as multidrug-resistant. Twelve KPC-carrying AGEs were sequences isolates, classified two groups: Tn7551 Tn6296-related elements. The clusters for enterotoxins tilimycin tilivalline, encompassing key regulators operons, present nearly all strains, incomplete exclusively observed clade 3 isolates. underscores global dissemination adaptability pasteurii, highlighting potential role reservoir emphasizing need robust surveillance mitigate public health impact.

Language: Английский

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Harnessing the human gut microbiota: an emerging frontier in combatting multidrug-resistant bacteria

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 17, 2025

Antimicrobial resistance (AMR) has become a major and escalating global health threat, undermining the effectiveness of current antibiotic antimicrobial therapies. The rise multidrug-resistant bacteria led to increasingly difficult-to-treat infections, resulting in higher morbidity, mortality, healthcare costs. Tackling this crisis requires development novel agents, optimization therapeutic strategies, initiatives infection surveillance control. Recent studies highlight crucial role human gut microbiota defending against AMR pathogens. A balanced protects body through mechanisms such as colonization resistance, positioning it key ally fight AMR. In contrast, dysbiosis disrupts defense, thereby facilitating persistence, colonization, dissemination resistant This review will explore how influence drug-resistant bacterial its involvement various types AMR-related potential for microbiota-targeted therapies, fecal transplantation, prebiotics, probiotics, phage therapy. Elucidating interactions between pathogens provide critical insights developing strategies prevent treat infections. While previous reviews have focused on general impact health, specifically look at latest research evolution spread AMR, highlighting strategies.

Language: Английский

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Microbiota-derived small molecule genotoxins: host interactions and ecological impact in the gut ecosystem

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: Nov. 18, 2024

The human intestinal tract is densely colonized by a microbial community that subject to intense competition. Bacteria in this complex habitat seek outcompete their neighbors for nutrients and eliminate competitors with antibacterial toxins. Antagonism can be mediated diverse effectors including toxic proteins small molecule inhibitors are released extracellularly or delivered specialized secretion systems targeted cells. Two prototypical microbiota-derived enterotoxins, colibactin tilimycin, the newly discovered family of indolimines represent an expanding group non-proteinaceous molecules which specifically target DNA. In addition cell killing, they generate mutations genome instability intoxicated microbes host cells alike. They have been studied detail because direct toxicity important etiological roles pathologies. Increasing evidence, however, reveals these commensal genotoxins also mediators interbacterial antagonism, impacts gut ecology. review, we illustrate functional versatility ecosystem.

Language: Английский

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