Understanding microbial-host interactions in the oral cavity is essential for elucidating oral disease pathogenesis and its systemic implications. In vitro bacteria-host cell coculture models have enabled fundamental studies to characterize bacterial infection and host responses in a reductionist yet reproducible manner. However, existing in vitro coculture models fail to establish conditions that are suitable for the growth of both mammalian cells and anaerobes, thereby hindering a comprehensive understanding of their interactions. Here, we present an asymmetric gas coculture system that simulates the oral microenvironment by maintaining distinct normoxic and anaerobic conditions for gingival epithelial cells and anaerobic bacteria, respectively. Using a key oral pathobiont, Fusobacterium nucleatum, as the primary test bed, we demonstrate that the system preserves bacterial viability and supports the integrity of telomerase-immortalized gingival keratinocytes. Compared to conventional models, this system enhanced bacterial invasion, elevated intracellular bacterial loads, and elicited more robust host pro-inflammatory responses, including increased secretion of CXCL10, IL-6, and IL-8. In addition, the model enabled precise evaluation of antibiotic efficacy against intracellular pathogens. Finally, we validate the ability of the asymmetric system to support the proliferation of a more oxygen-sensitive oral pathobiont, Porphyromonas gingivalis. These results underscore the utility of this coculture platform for studying oral microbial pathogenesis and screening therapeutics, offering a physiologically relevant approach to advance oral and systemic health research.
Coculture Techniques/methods* ; Humans ; Fusobacterium nucleatum/physiology* ; Gingiva/microbiology* ; Keratinocytes/microbiology* ; Host Microbial Interactions ; Mouth/microbiology* ; Host-Pathogen Interactions ; Epithelial Cells/microbiology* ; Cells, Cultured ; Porphyromonas gingivalis

The host-microbe co-metabolism system, generating diverse exogenous and endogenous bioactive molecules that influence the host's immune and metabolic functions, plays a crucial role in the pathogenesis of atherosclerosis. Recent studies have elucidated the interaction between natural medicines and this co-metabolism system. Upon oral administration, natural medicine ingredients can undergo transformation by gut microbiota, potentially enhancing their bioavailability or anti-atherogenic efficacy. Furthermore, natural medicines can exert anti-atherogenic effects via modulation of endogenous host-microbe co-metabolism. This review presents an updated understanding of the dual association between natural medicines and host-microbe co-metabolites. It explores the critical function of microbial exogenous metabolites derived from natural medicines and uncovers the mechanisms underlying natural medicines' intervention on key nodes of endogenous host-microbe co-metabolism. These insights may offer new perspectives for cardiovascular disease (CVD) treatment and guide future drug discovery efforts.
Humans ; Atherosclerosis/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Biological Products/therapeutic use* ; Animals ; Host Microbial Interactions/drug effects*

As specialized intracellular parasite, viruses have no ability to metabolize independently, so they completely depend on the metabolic mechanism of host cells. Viruses use the energy and precursors provided by the metabolic network of the host cells to drive their replication, assembly and release. Namely, viruses hijack the host cells metabolism to achieve their own replication and proliferation. In addition, viruses can also affect host cell metabolism by the expression of auxiliary metabolic genes (AMGs), affecting carbon, nitrogen, phosphorus, and sulfur cycles, and participate in microbial-driven biogeochemical cycling. This review summarizes the effect of viral infection on the host's core metabolic pathway from four aspects: cellular glucose metabolism, glutamine metabolism, fatty acid metabolism, and viral AMGs on host metabolism. It may facilitate in-depth understanding of virus-host interactions, and provide a theoretical basis for the treatment of viral diseases through metabolic intervention.
Humans ; Metabolic Networks and Pathways ; Virus Diseases ; Carbohydrate Metabolism ; Host Microbial Interactions ; Lipid Metabolism

Fecal microbiota transplantation (FMT) has become a research focus of biomedicine and clinical medicine in recent years. The clinical response from FMT for different diseases provided evidence for microbiota-host interactions associated with various disorders, including Clostridium difficile infection, inflammatory bowel disease, diabetes mellitus, cancer, liver cirrhosis, gut-brain disease and others. To discuss the experiences of using microbes to treat human diseases from ancient China to current era should be important in moving standardized FMT forward and achieving a better future. Here, we review the changing concept of microbiota transplantation from FMT to selective microbiota transplantation, methodology development of FMT and step-up FMT strategy based on literature and state experts' perspectives.
Clostridium Infections ; therapy ; Fecal Microbiota Transplantation ; methods ; standards ; Host Microbial Interactions ; Humans ; Inflammatory Bowel Diseases ; therapy ; Metabolic Diseases ; therapy

Saprolegniasis is one of the most devastating oomycete diseases in freshwater fish which is caused by species in the genus Saprolegnia including Saprolegnia parasitica. In this study, we isolated the strain of S. parasitica from diseased rainbow trout in Korea. Morphological and molecular based identification confirmed that isolated oomycete belongs to the member of S. parasitica, supported by its typical features including cotton-like mycelium, zoospores and phylogenetic analysis with internal transcribed spacer region. Pathogenicity of isolated S. parasitica was developed in embryo, juvenile, and adult zebrafish as a disease model. Host-pathogen interaction in adult zebrafish was investigated at transcriptional level. Upon infection with S. parasitica, pathogen/antigen recognition and signaling (TLR2, TLR4b, TLR5b, NOD1, and major histocompatibility complex class I), pro/anti-inflammatory cytokines (interleukin [IL]-1β, tumor necrosis factor α, IL-6, IL-8, interferon γ, IL-12, and IL-10), matrix metalloproteinase (MMP9 and MMP13), cell surface molecules (CD8⁺ and CD4⁺) and antioxidant enzymes (superoxide dismutase, catalase) related genes were differentially modulated at 3- and 12-hr post infection. As an anti-Saprolegnia agent, plant based lawsone was applied to investigate on the susceptibility of S. parasitica showing the minimum inhibitory concentration and percentage inhibition of radial growth as 200 μg/mL and 31.8%, respectively. Moreover, natural lawsone changed the membrane permeability of S. parasitica mycelium and caused irreversible damage and disintegration to the cellular membranes of S. parasitica. Transcriptional responses of the genes of S. parasitica mycelium exposed to lawsone were altered, indicating that lawsone could be a potential anti-S. parasitica agent for controlling S. parasitica infection.
Adult ; Cytokines ; Embryonic Structures ; Fresh Water ; Host-Pathogen Interactions ; Humans ; Interferons ; Interleukin-12 ; Interleukin-6 ; Interleukin-8 ; Korea* ; Major Histocompatibility Complex ; Membranes ; Microbial Sensitivity Tests ; Mycelium ; Oncorhynchus mykiss* ; Oomycetes ; Permeability ; Plants ; Saprolegnia* ; Tumor Necrosis Factor-alpha ; Virulence ; Zebrafish*