Search Results (2,777)

Widespread antibiotic use in aquaculture has increased selective pressure on resident bacterial communities, accelerating the emergence of resistance in key pathogens and raising concerns for animal health, environmental microbiomes, and food-chain safety. Reducing dependence on therapeutic antimicrobials requires alternative strategies that remain effective under the processing and biosafety constraints of intensive production systems, where recurrent bacterial diseases continue to cause substantial economic losses. Live probiotics, currently the most extensively studied microbiome-based intervention, have practical limitations, including reduced viability during feed pelleting and extrusion, transient gut colonization, strain-specific host responses, biosafety concerns related to horizontal transfer of antimicrobial-resistance genes, and variable regulatory requirements across regions. Postbiotics, defined as preparations of non-viable microbial biomass, with or without metabolites, that confer a demonstrated health benefit in the target host, and paraprobiotics, which emphasize inactivated whole-cell preparations that preserve surface-associated microbial molecular patterns, may help address several of these constraints. These approaches offer improved compositional definition, greater feed-processing stability, and a potentially more favorable biosafety profile. Because they are non-viable, their anti-pathogen effects do not depend on growth or competitive colonization but may instead involve preformed antimicrobial compounds retained in some preparations, interference with pathogen attachment, modulation of the intestinal environment, reinforcement of barrier function, and stimulation of host immune responses. This review synthesizes current evidence on postbiotics and paraprobiotics in aquaculture, with emphasis on structural classification, pattern-recognition receptor signaling, intestinal barrier function, innate immune priming, encapsulation technologies, and translational readiness. Taken together, available evidence supports postbiotics and paraprobiotics as promising, but not yet fully characterized, alternatives to live probiotics within antibiotic-reduction strategies for aquaculture. Progress toward commercial application will depend on resolving key questions related to dose–response relationships, processing stability in formulated feeds, and species-specific efficacy. Full article

The gut microbiome is a complex ecological system crucial to human physiology. Commensal microbes in the gut provide resistance against pathogenic colonization, mainly due to their metabolites. Though studies have revealed a few mechanisms of microbial metabolite-mediated colonization resistance, various commensal microbes in the gut produce versatile metabolites and confront different pathogens. To pave the way for microbial metabolite-based treatment, clarification of what microbes and derived metabolites contribute to colonization resistance is a central topic. This focused review addressed the nexus of the gut microbiome, microbial metabolites, and colonization resistance against three representative pathogens, namely Clostridioides difficile, Salmonella enterica subspecies enterica serovar Typhimurium, and vancomycin-resistant Enterococcus. Different microbes and microbial metabolites involved in colonization resistance against these pathogens are discussed. Microbial metabolites, mainly short-chain fatty acids, secondary bile acids, and bacteriocins, were included. The emerging role of signal molecules in combating pathogenic infections is also addressed. In contrast to others, we further discussed different strategies that can enhance microbial metabolite-mediated colonization resistance, such as precise microbial preparation, targeted proliferation of a protective metabolite-producing microbiome, regulation of dietary patterns to optimize metabolic homeostasis, enhancing the local concentration of metabolites in the gut, and host-matched intervention. Full article

Whether the extracts of Fomes fomentarius, Ganoderma applanatum and Trametes versicolor can inhibit the growth of Fusarium graminearum in vitro, reduce the severity of Fusarium head blight (FHB) and reduce fungal colonization of wheat seeds artificially infected with this pathogen were the questions that initiated this research. The mycelial growth of F. graminearum was significantly reduced after treatment with ethanol extracts of the studied white-rot fungi, from 43.1% with F. fomentarius to 53.2% with T. versicolor. Likewise, these extracts significantly reduced disease development in artificially infected wheat seeds. Disease severity was quantified using the Disease Severity Index (DSI). In fact, after artificial infection with F. graminearum of lines carrying effective resistance (Fhb7 locus) from an alien source and their treatment with mushroom extracts, disease severity was negligible, and seedling fitness was very high. The highest efficacy of 99.49% was recorded in the resistant line R6-1, carrying the Fhb7 allele from Thinopyrum elongatum (7E) following treatment with the T. versicolor extracts. Slightly lower efficacy values were obtained after treatment with G. applanatum (97.83%) and F. fomentarius (97.47%). The obtained results showed that the selected mushroom extracts can be used in F. graminearum control and support successful wheat cultivation in FHB-prone areas. Full article

The vocabulary of artificial intelligence has colonized human self-description. Terms historically reserved for conscious agents—intelligence, learning, understanding, creativity—now routinely designate computational processes that bear no phenomenological resemblance to the experiences that they originally named. This conceptual erosion is not merely semantic; it undermines our capacity to articulate what distinguishes human cognition from machine operation at a moment when that distinction matters most. This article develops a dual-path argument for the identification of irreducibly human capacities. A via negativa assembles four independent lines of formal and philosophical reasoning—Gödel’s incompleteness theorems, Turing’s halting problem, Searle’s Chinese Room, and the frame problem—that establish principled limits to what computation can achieve. A via positiva draws on phenomenology to positively characterize the structures of human existence that lie beyond those limits: embodiment, intersubjectivity, temporality, being-in-the-world, and subjective experience. The convergence of these independent paths—each pointing from its own starting point toward the same boundary—grounds a taxonomy of five Unique Human Faculties (creativity, moral judgment, self-determination, empathy, and sentience) that resist mechanization in principle. The article concludes that the burden of proof now lies with those who claim that formal computation can exhaust human understanding, and argues that the simulation–possession distinction provides a principled basis for restoring conceptual clarity to discourse about artificial intelligence. Full article

Enramycin is used as a dietary antimicrobial in young animals, but its effects on rabbit colonic ecology remain insufficiently characterized. This study evaluated the effects of enramycin in 60 weaned rabbits randomly assigned to a control or enramycin-treated group (60 mg/kg) for 14 days (n = 30/group). Clinical outcomes were evaluated in all rabbits, whereas paired colonic multi-omics profiling was performed in six randomly selected survivors per group with no recorded diarrhea. Enramycin reduced diarrhea incidence without affecting body-weight development, organ indices, or mortality. Metagenomic analysis revealed unchanged alpha diversity but significant alterations in microbial community structure, including decreased Verrucomicrobiota, Akkermansia, and Alistipes and increased Cyanobacteria and Avigastranaerophilus. Untargeted metabolomics identified 332 features meeting the predefined screening criteria, including 143 upregulated and 189 downregulated metabolites. Prominent pathway annotations included phenylpropanoid biosynthesis and arachidonic acid metabolism. Resistome analysis demonstrated that treatment drove shifts in streptothricin-, aminoglycoside- and glycopeptide-related resistance signatures. The integrated analysis identified associations between four selected genera and the top 30 differential metabolites. Overall, dietary enramycin was associated with a short-term reduction in diarrhea incidence and concurrent changes in selected colonic microbial, metabolic, and resistance gene features. These findings extend enramycin evaluation beyond conventional clinical outcomes and highlight the importance of considering broader ecological effects when assessing dietary antimicrobial exposure in weaned rabbits. Full article

Polysaccharides are well known for their immunomodulatory properties and gut microbiota-regulating functions; however, their digestive stability and structure-dependent biological mechanisms remain poorly understood. This study investigated the in vitro enzymatic resistance and intestinal regulatory effects of a novel L-β-galactoglucan (Mw 400–520 kDa) derived from Agrobacterium sp. FN01, and further evaluated the in vivo effects of its corresponding crude fermentation product on growth performance and intestinal metabolism in pigs. Twenty-seven-day-old weaned piglets were randomly allocated to three treatments, with 16 pens per treatment and 13 piglets per pen, and fed basal diets supplemented with 0, 200, or 400 mg/kg of the crude product. The results showed that L-β-galactoglucan exhibited strong resistance to pancreatic α-amylase and glucoamylase under the tested in vitro conditions, with minimal release of low-molecular-weight oligosaccharides during hydrolysis. The 400 mg/kg crude product supplementation significantly improved growth performance, reduced the feed-to-gain ratio, and increased the apparent total tract digestibility of dry matter, crude protein, crude fat, and gross energy (p < 0.05). In addition, dietary supplementation with this crude product increased intestinal microbial diversity, enriched Halalkalibacter urbisdiaboli, and increased colonic concentrations of isobutyrate and isovalerate (p < 0.05). Functional metagenomic analysis further revealed enhanced microbial carbohydrate metabolism and energy metabolic pathways. In conclusion, under the in vitro conditions tested in this study, the novel L-β-galactoglucan exhibited resistance to the two tested enzymes. In the pig trial, this polysaccharide improved growth performance and nutrient utilization, and modulated the intestinal microbial composition. These observations suggest that the fermentation product may be promising for animal feeding applications. Full article

Clostridioides difficile infection (CDI) remains a major cause of antibiotic-associated diarrhea, with recurrence largely driven by disruption of the gut microbiota and impaired colonization resistance. Bile acids have emerged as key mediators in this process, as primary conjugated bile acids promote C. difficile spore germination, whereas microbiota-derived secondary bile acids can inhibit germination, vegetative growth, and toxin activity. Diet further modulates CDI susceptibility by shaping microbial composition, short-chain fatty acid production, bile acid transformation, epithelial barrier integrity, and intestinal inflammation. Western-style diets, and low fiber intake, may favor dysbiosis and a bile acid profile permissive to CDI, while fiber-rich and Mediterranean-type dietary patterns may support beneficial anaerobes, microbial metabolites, and mucosal resilience. This narrative review summarizes current evidence on the bile acid–diet–microbiome axis in CDI pathogenesis, recurrence, and therapy. It also discusses standard treatment limitations, microbiome-based therapeutics, dietary interventions, and emerging bile acid-targeted strategies. Understanding this axis may support future precision approaches aimed not only at suppressing C. difficile, but also at restoring microbiota function and durable colonization resistance. Full article

The respiratory tract is a dynamic biological interface where microbiome, environmental exposure, epithelial integrity, and host metabolic regulation converge to maintain pulmonary homeostasis. Once considered sterile, the lung is now recognized as a low-biomass yet structured microbial ecosystem that contributes to immune calibration, colonization resistance, epithelial barrier function, and tissue resilience. Disruption of this equilibrium, known as pulmonary dysbiosis, has been increasingly associated with acute and chronic lung diseases, including cystic fibrosis, chronic obstructive pulmonary disease, acute respiratory distress syndrome, idiopathic pulmonary fibrosis, asthma, bronchiectasis, and lung cancer. In parallel, mitochondria have emerged as central regulators of pulmonary cell function, extending beyond ATP production to control redox signaling, apoptosis, innate immunity, epithelial repair, and inflammatory responses. This review examines the bidirectional crosstalk between the respiratory microbiome and mitochondria as an integrated pathogenic axis in lung disease. Dysbiotic microbial communities and respiratory pathogens can induce mitochondrial stress through toxins, virulence factors, microbial metabolites, and pattern-recognition receptor activation, leading to mitochondrial alteration and the release of mitochondrial damage-associated molecular patterns. Conversely, dysfunctional mitochondria reshape the pulmonary microenvironment by altering oxygen consumption, nutrient availability, cytokine production, redox balance, and barrier repair, thereby favoring pathogen persistence and chronic inflammation. Understanding mitochondria–microbiome interactions may support precision medicine strategies that integrate microbial, metabolic, inflammatory, and bioenergetic biomarkers to improve the diagnosis, prognosis, and treatment of inflammatory-related lung diseases. Full article

Titanium and its alloys are widely used in cardiovascular devices because of their favorable mechanical properties, corrosion resistance, and biocompatibility. Nevertheless, their surfaces do not fully prevent nonspecific protein adsorption, platelet activation, thrombosis, bacterial colonization, or long-term degradation under physiological conditions. Silicon-nitride-based (SiN_x) coatings represent a promising strategy for addressing these limitations by combining chemical stability, mechanical durability, hemocompatibility, and antibacterial activity. This review critically examines silicon-nitride-based (SiN_x) coatings on titanium for cardiovascular applications, focusing on deposition technologies, interfacial phenomena, surface characteristics, and biological performance. Particular attention is given to physical vapor deposition parameters, coating adhesion, residual stresses, interfacial reactions, corrosion resistance, and mechanical stability. Relationships between surface chemistry, wettability, protein adsorption, platelet response, hemolysis, and cellular behavior are discussed, alongside the effects of static and dynamic testing conditions. SiN_x is also compared with Au, TiN, TiO₂, ZrN, and silicon carbide-based coatings. Despite encouraging in vitro results, clinical translation remains limited by insufficient standardization, scarce long-term and flow-dependent data, and an incomplete understanding of degradation mechanisms. Future studies should integrate interface engineering with microfluidic models, standardized hemocompatibility testing, artificial intelligence-assisted optimization of process–structure–property–biological response relationships, and regulatory considerations to support the safe clinical translation of SiN_x-coated cardiovascular devices. Full article

This paper judges Eurocentric mathematics and its role in sustaining colonial inequalities. Drawing on Fanon’s work and a redefined concept of capital, we highlight the taken-away power (and knowledge) within margins, such as Indigenous communities, which influences the maintenance or diminution of the capital of taken-for-granted social structures. We present two examples. The first highlights an initiative that is reclaiming Indigenous mathematical knowledge by actively resisting colonization. The second illustrates the dangers of seemingly well-intentioned initiatives that inadvertently reinforce knowledge colonization, despite translating workbooks into Indigenous languages. We conclude by emphasizing the need to move beyond simply including knowledge from the margins in the existing Eurocentric framework, and to instead recognize and build on the transformative power of those margins to reshape and redefine the very nature of capital, power and knowledge. Full article

Immune checkpoint blockade has changed the management of several digestive system cancers, but its impact is highly context dependent. This review evaluates evidence for esophageal, gastric and gastroesophageal junction, colorectal, hepatocellular, biliary tract and gallbladder, and pancreatic cancers. Randomized phase III trials have established chemoimmunotherapy or dual-checkpoint strategies in advanced esophageal cancer, biomarker- and regimen-dependent first-line therapy in gastric cancer, PD-1-based therapy for MSI-H/dMMR colorectal cancer, atezolizumab–bevacizumab and STRIDE for unresectable hepatocellular carcinoma, and chemoimmunotherapy for advanced biliary tract cancer. Recent results also expand perioperative treatment: neoadjuvant checkpoint blockade produces high pathological response rates in dMMR colon cancer, adjuvant atezolizumab plus mFOLFOX6 improves disease-free survival in stage III dMMR colon cancer, and perioperative serplulimab improves event-free survival in PD-L1-positive resectable gastric cancer. These advances coexist with important negative findings. Pembrolizumab-containing therapy did not meet superiority end points in KEYNOTE-062, the initial adjuvant signal in IMbrave050 was not sustained, and unselected pancreatic ductal adenocarcinoma remains largely resistant to checkpoint blockade. Early vaccine, cellular, TIGIT, radiomics, spatial, and multi-omics studies remain hypothesis-generating and require external or randomized validation. Clinical interpretation should integrate evidence maturity, biomarker validity, immune-related toxicity, patient-reported outcomes, cost, access, and manufacturing demands rather than response rate alone. Full article

Background/Objectives: Certain strains of Lactobacillus acidophilus are widely used as probiotics. However, their functional potential for female reproductive tract health remains insufficiently characterized. While most studies have focused on individual strains, the distribution of putative probiotic-associated genes across the species remains unclear. This study aimed to evaluate the vaginal probiotic potential of Lb. acidophilus using population genomic analysis and comparative phenotypic characterization. Methods: Pan-genomic analysis was performed on 109 Lb. acidophilus genomes (107 public genomes and 2 vaginal isolates). Putative probiotic-associated gene clusters were identified by functional annotation, categorized into functional modules, and compared among ecological-origin groups. Two vaginal isolates (strains A2 and A3) were characterized in vitro for growth under different pH conditions, cell surface hydrophobicity, lactic acid and hydrogen peroxide production, antimicrobial activity, hemolysis, and antimicrobial susceptibility. Results: The Lb. acidophilus pan-genome was closed, with 1782 of 1902 gene clusters (93.69%) classified as core. Thirty-six putative probiotic-associated gene clusters were identified and grouped into four modules: environmental tolerance, adhesion/colonization, exopolysaccharide/biofilm synthesis, and nutrient metabolism/microbial competition. Thirty-four of the 36 gene clusters were present in all 109 genomes, and no general ecological origin-specific distribution pattern was observed. Three bacteriocin-related gene clusters were conserved across all genomes. A2 and A3 exhibited similar lactic acid production and growth patterns at pH 4–6. Both produced relatively low amounts of hydrogen peroxide compared with the reference strains. A3 showed higher cell surface hydrophobicity and moderate inhibition against Gardnerella vaginalis, while A2 showed no inhibition of this organism. Both isolates were non-hemolytic, and were susceptible to vancomycin and linezolid, resistant to clindamycin, and non-susceptible to daptomycin. No acquired antibiotic resistance genes were detected. Conclusions: Most putative probiotic-associated gene clusters were conserved across the Lb. acidophilus population, whereas A2 and A3 showed strain-dependent phenotypic differences. These findings support combining population genomic analysis with strain-level phenotypic testing when selecting Lb. acidophilus candidates for bacterial vaginal infections. Full article

Campylobacter jejuni and Campylobacter coli account for most recognized cases of human campylobacteriosis. For C. coli, gene-carriage surveys often stand in for direct tests of function; this distinction is maintained throughout the review. Virulence is discussed as a sequence of events rather than as a catalogue of factors. Motility and adhesion have the most reproducible support during colonization and epithelial contact, whereas biofilm formation, quorum sensing, and T6SS-associated phenotypes vary substantially across strains and models. We then consider host–cell injury, persistence, transmission, and the uncommon post-infectious outcomes linked to sialylated LOS. Antimicrobial resistance is treated in parallel, with emphasis on target-site change, ribosomal protection or methylation, enzymatic inactivation, and CmeABC-mediated efflux. The One Health model places both species within overlapping animal, food, and environmental reservoirs rather than assigning C. jejuni exclusively to poultry or C. coli to swine. A narrower conclusion emerges from the resistance-fitness literature: gyrA Thr-86-Ile and CmeABC can alter colonization or competitive fitness, but the available data do not show that resistance generally predicts more severe human disease. This distinction frames the proposed priorities for surveillance and intervention. Full article

Extraintestinal pathogenic Escherichia coli (ExPEC) is among the bacterial pathogens associated with infections of the female and male reproductive tracts, where it may contribute to inflammatory processes and impaired reproductive function. In this context, neutrophils constitute a critical component of host defense through the release of neutrophil extracellular traps (NETs), web-like structures composed of decondensed chromatin, histones, and antimicrobial proteins that capture and eliminate invading microorganisms. However, the interaction between E. coli and NETs is highly dynamic, as the bacterium has evolved immune-evasion mechanisms that facilitate persistence within the host. This raises a critical paradox: NETs may shift from an antimicrobial defense mechanism to a microenvironmental factor that inadvertently favors bacterial persistence and chronic inflammation. This review synthesizes current evidence on the colonization, virulence, and immune-evasion mechanisms of E. coli in the reproductive tract, with particular emphasis on the modulation of NETosis, biofilm formation, and their contribution to antimicrobial resistance. We further discuss the dual role of NETs as an innate immune defense mechanism and, conversely, as a potential contributor to tissue injury, oxidative stress, and chronic inflammation when dysregulated. Understanding the interplay among E. coli, extracellular traps, and antimicrobial resistance provides a valuable conceptual framework for the development of novel therapeutic approaches aimed at limiting bacterial persistence, preserving reproductive function, and addressing the growing global threat of antimicrobial resistance. Full article

Background/Objectives: Infection with Bordetella pertussis causes whooping cough. CD4⁺ T cell responses depend on bacterial peptides displayed by HLA class II, yet allele- and strain-resolved maps of naturally processed B. pertussis HLA-DR ligands remain limited. We sought to define which antigens yield HLA-DR ligands in a human macrophage model and whether presentation is skewed by HLA-DR molecule and bacterial strain. Methods: THP-1–derived macrophages were pulsed with whole-cell lysates of B. pertussis vaccine/reference strain Tohama I or clinical isolate D420. HLA-DR was immunoaffinity purified; eluted peptides were identified by LC-MS/MS and assigned to HLA-DR molecules encoded by HLA-DRB1*01:01, HLA-DRB1*15:01, and HLA-DRB5*01:01. Results: We identified 63 B. pertussis peptide ligands from 29 source proteins. Presentation was skewed by HLA-DR molecule: DRB1*01:01 accounted for 37 ligands from 21 antigens, DRB1*15:01 for 22 from 7, and DRB5*01:01 for 4 from 4. Most source proteins contributed ligands primarily to one HLA-DR molecule, so an antigen that supplies peptides to one DR product need not supply peptides to another. Strain further partitioned the ligandome: 32 ligands unique to Tohama I, 12 to D420, and only 19 from 8 proteins with both lysates. Only three antigens contributed ligands to both DRB1*01:01 and DRB1*15:01; two of these, pertactin and filamentous hemagglutinin, are components of current acellular pertussis vaccines. Conclusions: B. pertussis HLA-DR ligandomes are jointly shaped by bacterial strain and HLA-DR molecule. Antigens can interact selectively with individual HLA-DR products, and peptides from a given antigen may be recovered after pulse with one strain but not another. These findings support HLA-DR and strain-aware interpretation of class II presentation and nominate BrkA autotransporter (Bordetella resistance to killing A), outer membrane protein A (OmpA), tracheal colonization factor (TcfA), and a divalent metal transporter (DMT) family transporter for follow-up. Full article