Obstructive sleep apnea (OSA) exposes tissues to recurrent intermittent hypoxia (IH) and is associated with multisystem morbidity. Growing evidence implicates the gut microbiota and microbial metabolism in these consequences, but their contribution to target-organ injury remains uncertain. This narrative review examines how IH remodels the intestinal environment and evaluates the evidence linking these changes to systemic injury, distinguishing preclinical experimental findings from human clinical observations. IH can disturb intestinal oxygen homeostasis, impair epithelial barrier function, and alter microbial and host–microbial metabolic pathways involving short-chain fatty acids, bile acids, and trimethylamine N-oxide. These changes may influence distant tissues through metabolic signaling and immune activation. Preclinical studies support a functional microbial contribution to selected cardiovascular, metabolic, and neurocognitive phenotypes, but mechanistic resolution and applicability vary with exposure conditions, diet, and host background. Human studies remain predominantly observational and do not establish microbial mediation of OSA-related organ injury. Overall, the gut microbiota is best regarded as a context-dependent contributor and amplifier of IH-related injury, rather than a universal mediator. A focus on microbial function and host–microbial co-metabolism may be more informative than inconsistent taxonomic signatures. Longitudinal studies and targeted interventions are needed to establish clinical relevance and determine whether microbiome-directed approaches can complement established OSA treatment.
BackgroundSepsis remains a major cause of mortality worldwide, and biomarkers that integrate inflammatory dysregulation, immune-cell localization, and prognostic relevance remain limited. To identify a candidate molecule linked to myeloid immune responses in sepsis, we performed an integrated analysis of public bulk transcriptomic datasets, single-cell RNA sequencing data, a small exploratory clinical RNA-sequencing cohort, and compound screening analyses.ResultsDifferential expression analysis and meta-analysis across public datasets identified THBS1 as a consistently altered transcript in sepsis. In a small exploratory peripheral-blood transcriptomic cohort comprising 23 patients with sepsis and 10 healthy controls, THBS1 was selected for downstream analysis on the basis of its position in the public-data protein–protein interaction network and the subsequent THBS1-focused analyses. The reused clinical RNA-sequencing cohort was retained only as an exploratory description and was not used to claim independent validation. Single-cell analysis suggested that THBS1 expression was more prominent in subsets of myeloid-related cell populations. Survival analysis in an external dataset indicated that high THBS1 expression was associated with poorer outcomes, but this finding should be interpreted as exploratory because formal adjustment for disease severity was not possible. Candidate compounds associated with THBS1 were further prioritized by database mining and molecular docking.ConclusionsThis study provides transcriptomic and computational evidence suggesting that THBS1 may be associated with myeloid-related immune activity and adverse prognosis in sepsis. Because the clinical cohort was small, protein-level validation and functional experiments were not performed, and substantial heterogeneity was observed across public datasets, these findings should be interpreted as preliminary and hypothesis-generating.
Staphylococcus aureus is one of the main etiological agents of acute mastitis during lactation, and its ability to persist in biofilms can compromise conventional antimicrobial treatments. Lactic acid bacteria (LAB) have emerged as promising probiotic candidates for mastitis management, but the molecular mechanisms underlying their interaction with S. aureus remain poorly understood. This study aimed to evaluate the ability of three LAB strains (Limosilactobacillus fermentum I7, Limosilactobacillus reuteri 7SNG3–30 and Ligilactobacillus salivarius 22SNG3-30) to interfere with mature biofilms formed by two mastitis-associated S. aureus strains, SA4 and SA55, and to characterize the associated transcriptional responses. The LAB strains were able to colonize preformed 24-h S. aureus biofilms, eventually dominating the mixed-species communities and reducing the attached staphylococcal population. RT-qPCR showed limited transcriptional changes after 4 h of LAB exposure, followed by a broader 16-h response characterized by induction of the stress/adaptation marker uspA and repression of genes related to quorum sensing, virulence, biofilm matrix production and iron acquisition. RNA-seq analysis of SA4 biofilms exposed to LAB for 16 h confirmed extensive transcriptional remodeling in S. aureus and revealed a conserved response across the three LAB treatments, including activation of stress, proteostasis, energy metabolism and arginine catabolism functions, together with repression of surface-associated, matrix-related, metal acquisition and virulence-associated pathways. In contrast, LAB transcriptomic responses were more moderate and strain-dependent, suggesting different metabolic, nutrient-acquisition and envelope-adaptation strategies during biofilm-associated interactions. Overall, these findings suggest that these LAB strains can displace mastitis-associated S. aureus from mature biofilms and promote a coordinated transcriptional shift toward stress adaptation and attenuation of virulence- and persistence-associated functions.
Cytotoxic injury to gill epithelial cells is a major consequence of pathogen infection and can compromise barrier function in aquaculture species. Edwardsiella tarda is an important bacterial pathogen in aquaculture. Infection of gill epithelial cells can damage barrier integrity, induce cytotoxicity, and trigger oxidative and inflammatory stress responses. This study evaluated whether AuraAqua (Aq), an organic acid-based antimicrobial mixture, protects RTgill-W1 cells from E. tarda-induced cytotoxicity and the associated inflammatory and oxidative stress responses. Aq showed a minimum inhibitory concentration of 1% and a minimum bactericidal concentration of 2%. Aq treatment reduced E. tarda adhesion and intracellular bacterial recovery, indicating impaired early host-pathogen interactions. Importantly, Aq was not directly cytotoxic to RTgill-W1 cells at the tested concentrations (0, 0.1, 0.2, 0.5, 1 and 2%) and reduced infection-associated LDH release while preserving cell viability and transepithelial electrical resistance. These outcomes were accompanied by increased expression of tight-junction-associated genes, including cldn-10e, cldn-30, and zo-1. During infection, Aq enhanced intracellular glutathione (GSH) levels, reduced superoxide dismutase (SOD) and catalase (CAT) activity, decreased H2O2 accumulation, and decreased NF-κB p65 activation. Aq also significantly downregulated IL-8, IL-1β, and TNF-α expression in infected cells. Together, these findings show that Aq can stimulate increased endogenous GSH production, which primarily protects RTgill-W1 cells and limits E. tarda-induced cytotoxic injury. This strengthens antioxidant defence, maintains epithelial barrier integrity, and suppresses NF-κB-associated inflammatory signalling.
