Search Results (456)

Enteropathogenic Escherichia coli (EPEC) disrupts intestinal barrier integrity, induces inflammation, and alters gut microbial balance, leading to diarrhea and growth impairment. Probiotics are considered promising alternatives to antibiotics for managing enteric infections, yet the functional properties and underlying mechanisms of feline-derived strains remain unclear. This study evaluated the protective effects of Ligilactobacillus (L.) agilis ZY25 and L. salivarius ZY35, isolated from healthy cats, against EPEC-induced intestinal injury in C57BL/6 mice, with a focus on barrier function, immune modulation, and microbial homeostasis. In this 21-day experiment, 48 mice were assigned to six groups (n = 8/group): control, EPEC model (MOD), chlortetracycline treatment (CTC), probiotic treatment (PRO-T; post-infection only), probiotic pre-treatment (PRO-P; pre-infection only), and continuous probiotic supplementation (PRO; pre- and post-infection). EPEC challenge (0.2 mL; 1 × 10⁹ CFU/mL) was performed daily during experimental days 8–14. EPEC challenge resulted in weight loss (p < 0.05), increased (p < 0.05) diarrhea incidence, elevated (p < 0.05) serum D-lactate, diamine oxidase, and lipopolysaccharide levels, impaired intestinal morphology, immune imbalance, and microbial dysbiosis. Probiotic administration alleviated these alterations, as evidenced by restored intestinal morphology, reduced serum markers of barrier permeability (D-lactate, DAO, LPS), enhanced systemic immunoglobulins (IgA, IgG, IgM), a balanced cytokine profile (increased IL-4, IL-10; decreased TNF-α, IL-6, IL-1β, IFN-γ, CRP), and modulation of the gut microbiota (enrichment of beneficial taxa such as Lachnospiraceae_NK4A136_group and suppression of pro-inflammatory Desulfovibrio). The continuous supplementation regimen (PRO) produced the most consistent improvements among the three intervention strategies tested. These findings suggest that feline-derived probiotics mitigate EPEC-induced intestinal dysfunction, accompanied by improved barrier-related indices, immune rebalancing, and microbial stabilization, thereby providing proof-of-concept evidence for their further evaluation in feline gastrointestinal health. Full article

Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder characterized by progressive motor and non-motor manifestations, including early gastrointestinal dysfunction. Growing evidence implicates the gut microbiota as an active modulator of host immune tone and neurodegenerative vulnerability, extending beyond descriptive taxonomic associations toward functional and metabolic mechanisms. PD-associated dysbiosis is consistently characterized by altered microbial functional capacity, including reduced short-chain fatty acid (SCFA) production, enrichment of pro-inflammatory metabolic traits, and sustained immune stimulation at the intestinal interface. These shifts promote chronic low-grade inflammation and intestinal barrier perturbations, creating conditions that may facilitate abnormal α-synuclein aggregation within the enteric nervous system. Current management predominantly relies on dopaminergic replacement and related symptomatic strategies, such as levodopa combinations, dopamine agonists, monoamine oxidase-B and catechol-O-methyltransferase (COMT) inhibitors, and device-aided therapies, which alleviate symptoms but do not halt underlying neurodegeneration or modify long-term disease course. These therapeutic limitations have intensified interest in upstream mechanisms that might be amenable to disease-modifying interventions, particularly those arising at the level of the gut microbiota and gut–immune–brain axis. This narrative review integrates clinical, metagenomic, metabolomic, and mechanistic evidence to propose a unified model in which microbiota-driven immune and metabolic perturbations may act as upstream drivers converging on α-synuclein pathology, neuroinflammation, and neurovascular dysfunction. Full article

The heart–brain axis is a bidirectional communication network composed of neural, humoral, and immune pathways that sustain cardiovascular and brain homeostasis. There is mounting evidence that viral myocarditis—a prototype of inflammatory heart disease—acts beyond the myocardium, triggering systemic immune cascades that lead to central nervous system (CNS) involvement. This involvement creates an inflammatory continuum in which cardiac damage and neuroinflammation reinforce each other via common cytokine and molecular mediators. Central mediators in this axis are the proinflammatory cytokines IL-1β, IL-6, tumor necrosis factor (TNF)-α, IL-17, IL-23, and IL-33. These cytokines are released by infected cardiomyocytes and immune cells during myocarditis, inducing endothelial cell (EC) activation, and causing blood–brain barrier (BBB) disruption. Simultaneously, TLR/NF-κB signaling and the stability of endothelial junctions are modulated by regulatory microRNAs such as miR-155 and miR-146a/b, which respectively enhance or attenuate inflammatory signals. Disruption of the BBB allows cytokines and immune cells to enter the brain parenchyma, where they activate microglia and astrocytes through NF-κB-dependent pathways. The resultant neuroinflammation disrupts autonomic equilibrium and leads to sympathetic overdrive, arrhythmogenesis, and overall worsening of cardiac injury, thus forming a self-perpetuating inflammatory cycle between the heart and the brain. Selective modulation of cytokines (anti-IL-1β, IL-6 receptor antagonists, and TNF-α modulators), blockade of the NLRP3 inflammasome, and miRNA therapy (anti-miR-155 and miR-146a mimics) are potential approaches for interrupting the heart–brain inflammatory circuit. In addition, neurotrophic therapies preserving BBB integrity may reduce secondary neuronal damage. Therefore, a future precision cardio-neuroprotective paradigm will rely on the integration of anti-inflammatory, molecular, and neurovascular strategies aimed at limiting systemic cytokine propagation and restoring bidirectional homeostasis through the heart–brain axis. Full article

Heat stress (HS) occurs when animals are unable to effectively dissipate excess body heat, leading to increased core temperature and physiological imbalance. In mammals, HS negatively affects female reproduction. Infertility associated with HS is well documented in swine and is increasingly recognized in other mammals, including humans. HS disrupts several systemic processes that are essential for normal reproductive function, including endocrine regulation, nutrient metabolism, immune activity, and intestinal barrier integrity. Reduced feed intake and changes in metabolic hormones such as insulin and prolactin can impair ovarian function. Increased intestinal permeability during HS may allow bacterial endotoxins to enter the bloodstream, triggering inflammation that further compromises reproductive physiology. At the ovarian level, HS alters key cellular pathways involved in cell survival and metabolism, including Janus Kinase/Signal Transducer and Activator of Transcription (JAK–STAT), Phosphoinositide 3-Kinase/Protein Kinase B (PI3K/AKT), oxidative stress responses, autophagy, apoptosis, and heat shock protein expression. These changes disrupt follicular development, hormone production, oocyte quality, and corpus luteum function, resulting in reduced conception rates and increased embryonic loss. This review summarizes current knowledge of systemic and ovarian mechanisms by which HS impairs female reproduction in pigs and identifies areas requiring further investigation to improve fertility under increasing environmental temperatures. Full article

Clopidogrel has been the most commonly used therapy for preventing secondary cardiovascular events since 1997 by inhibiting the purinergic receptor P2Y, G-protein coupled, 12 protein receptor (P2RY12). P2RY12 is critical for microglia function in the brain, where it facilitates repair processes following injury. Under normal conditions, the blood-brain barrier (BBB) prevents peripheral drugs like clopidogrel from entering the brain. However, stroke-induced BBB disruption may allow clopidogrel to interfere with neural recovery by impairing microglia activity. Recently, we demonstrated that clopidogrel worsened cognitive outcomes in young mice after stroke. In this study, we examined the effects of clopidogrel on aged mice, focusing on survival, body weight, neurovascular changes, immune response, and amyloid beta accumulation. Aged male mice underwent photothrombotic stroke (or sham surgery) and received daily clopidogrel or control treatment for 14 days. On day 15, brain tissue was analyzed. Clopidogrel treatment significantly reduced survival and body weight, decreased vessel density, increased vascular permeability, altered microglia activity, and increased amyloid beta levels in the peri-infarct region. Notably, some of these effects were not observed in young mice. These results suggest that BBB disruption in stroke mice enables clopidogrel to enter the central nervous system, where it impairs microglia-mediated restoration of BBB integrity and promotes amyloid accumulation, factors that may contribute to worsened cognitive recovery. This study raises the possibility that clopidogrel may similarly cross the BBB in older stroke patients, impacting microglial function, and emphasizes the need for further research into its mechanisms of action. Full article

Background/Objectives: Porcine epidemic diarrhea (PED) is a highly contagious enteric disease caused by porcine epidemic diarrhea virus (PEDV) and is associated with severe clinical signs and high mortality in neonatal piglets. Vaccination is an important strategy for PED control through the induction of humoral immunity. This study aimed to compare immune responses induced by inactivated and live-attenuated PEDV vaccines and to evaluate a heterologous prime-boost vaccination strategy in PEDV-naïve replacement gilts. Methods: Twenty-four PEDV-naïve replacement gilts were randomly assigned to four groups: unvaccinated control, inactivated vaccine administered twice (K/K), live-attenuated vaccine administered twice (L/L), and live-attenuated priming followed by an inactivated booster (L/K). Pigs received two intramuscular vaccinations at 16 weeks of age and two weeks later. Serum samples collected up to 42 days post-vaccination were analyzed for PEDV-specific IgG and IgA antibodies by ELISA, and serum-neutralizing antibody titers were determined using a serum neutralization test. Results: The L/K regimen induced the highest PEDV-specific IgG responses, with peak levels at day 28 post-vaccination that were significantly higher than those in the K/K and control groups. Serum-neutralizing antibody titers were significantly higher in the L/K and L/L groups than in the K/K and control groups. Serum IgA responses were low and transient across all vaccination groups. Conclusions: A heterologous prime-boost vaccination strategy using a live-attenuated PEDV vaccine followed by an inactivated booster induces strong systemic humoral immune responses in replacement gilts and represents a promising approach for PEDV vaccination programs. Full article

Background/Objectives: Traumatic brain injury (TBI) is a significant public health concern resulting in physical, cognitive, and behavioral impairments. Emerging evidence highlights a bidirectional relationship between brain injury and gut health, known as the brain–gut axis. This paper provides a comprehensive review of current literature exploring the relationship between TBI and various gastrointestinal (GI) pathologies, examining how brain injuries contribute to GI dysfunction and how gut health influences neurorecovery. Methods: A comprehensive search of peer-reviewed articles was conducted between March and June 2025 using databases including PubMed, Scopus, and Cochrane. Studies from 2010 onwards involving human subjects were screened. Search terms included combinations of “traumatic brain injury,” “TBI,” and “[gastrointestinal pathology].” Data regarding study design, population, GI outcomes, and proposed mechanisms were analyzed. Results: TBI triggers secondary injury cascades, including neuroinflammation, dysautonomia, and gut microbiome dysbiosis. The review identifies a wide spectrum of TBI-associated GI disorders, including dysphagia, esophageal disorders, gastric disorders, and intestinal disorders. Bowel dysfunction, manifesting as constipation or incontinence, is prevalent due to neurogenic factors and cognitive impairments. Additionally, metabolic dysregulation following TBI leads to malnutrition, hyperglycemia, and hypoglycemia, all of which impact morbidity. Conclusions: The GI system is integrally connected to TBI recovery through immune modulation and nutrient absorption. Dysfunction within the brain–gut axis, specifically altered motility, permeability, and inflammation, contributes to secondary brain injury and impedes neurological outcomes. Clinical assessment of GI dysfunction should be integrated into routine TBI care. Therapeutic strategies, including early enteral nutrition, are essential to optimize recovery and reduce systemic inflammation. Full article

When nerves are severed, such as during traumatic injury, an acute injury state is induced, characterized by biological and physical changes in the proximal and distal stumps. Beyond the initial injury phase, over a time frame of weeks to months, nerves that remain unrepaired progressively enter a chronic injury state, characterized by a change in the extracellular matrix structure of the distal stump, the down-regulation of neurotrophic factors and the loss of macrophages’ and Schwann cells’ ability to clear out degraded axons and myelin. There are also potential systemic impacts away from the site of injury, including in end organs such as muscle and bone. The literature suggests that several of these processes may be strongly influenced by innate and adaptive immune system responses, including a major role for complement pathways. This review details evidence in favor of such a possibility, as well as knowledge gaps and areas for future investigation. Full article

Type 2 diabetes and insulin resistance are increasingly recognized as conditions influenced not only by genetic and lifestyle factors but also by infectious and microbial exposures. Diarrheagenic pathogens, including enterotoxigenic, enteroaggregative, and enterohemorrhagic Escherichia coli, as well as other enteric microorganisms, disrupt the gut microbiota and compromise intestinal barrier integrity. These alterations promote dysbiosis, increased intestinal permeability, and systemic exposure to lipopolysaccharides and other microbial products, leading to metabolic endotoxemia and chronic low-grade inflammation. In parallel, pathogen-induced modulation of host immune responses contributes to adipose tissue inflammation, mitochondrial dysfunction, and impaired insulin signaling. This review summarizes current evidence linking diarrheagenic pathogens to insulin resistance, with emphasis on the microbiota–immune–metabolism axis. Understanding these interactions highlights novel perspectives on the pathogenesis of insulin resistance and suggests that targeted modulation of the gut microbiota or reduction in pathogen-driven inflammation may represent therapeutic opportunities to improve metabolic outcomes. Full article

S. Typhimurium infection has the capacity to elicit enteric inflammation and metabolic dysfunction among poultry. Prior research conducted by our laboratory observed an increase in LXA4 titers within the gut of Wenchang chickens following infection with S. Typhimurium. Based on this observation, the present study analyzed the changes in body weight, immune organ indices, the levels of intestinal inflammatory cytokines, as well as cyclooxygenase-2 (COX-2) expression in Wenchang chickens before and after infection. The findings indicated that S. Typhimurium infection led to reduced body weight and significantly decreased thymus and bursa indices. Furthermore, a significant elevation was observed in the transcript levels of pro-inflammatory mediators, including IL-1β, along with IL-6, and TNF-α, concurrently with an increase in the mRNA transcript levels of the enzyme COX-2. Treatment with LXA4 attenuated these alterations and effectively alleviated the inflammatory response. Additionally, an in vitro system was employed to validate the anti-inflammatory properties of LXA₄ against S. Typhimurium-induced inflammation in chicken HD11 macrophages. The results demonstrated that LXA4 attenuated the transcript levels of IL-1β, as well as IL-6, TNF-α, and COX-2, at various intervals (2, 12, and 24 h), thereby alleviating inflammation elicited by S. Typhimurium challenge. We employed the LXA4 receptor antagonist Boc-2 to explore the ALX/FPR2 signaling axis and noted the successful neutralization of LXA4-mediated anti-inflammatory properties by this antagonist in S. Typhimurium–challenged HD11 macrophages. Collectively, these findings indicate that S. Typhimurium triggers pro-inflammatory reactions across both in vivo chicken models and in vitro HD11 macrophage systems, whereas LXA4 effectively mitigates this inflammatory process. This research establishes the conceptual underpinnings necessary to advance the design of therapeutic modalities aimed at counteracting S. Typhimurium challenges within poultry populations. Full article

The authors hypothesize that idiopathic Parkinson’s disease may result from an alteration in microvascular flow at a “critical point” in the nervous system that is characterized by pigmented cells that express neuromelanin and/or lipofuscin. “Critical points” include the olfactory epithelium/bulb, the autonomic nervous system, the enteric nervous system, the prefrontal–cortico-pontine network, and the amygdala. Hypoxia–ischemia following blood flow disturbance would recruit and activate leukocytes and induce the infiltration of peripheral immune cells into neural tissue. The excess of toxic factors produced by hyperactive immune cells, such as myeloperoxidase and its derivatives, would cause the oxidation of lipids, proteins, and biogenic monoamines such as dopamine, which in turn would facilitate the accumulation and precipitation of neuromelanin, lipofuscin, and alpha-synuclein. In addition, neuromelanin and lipofuscin precipitates may accentuate the misfolding and aggregation of alpha-synuclein. This “amplification” mechanism could help explain the crucial role of pigmented neurons in the onset of Parkinson’s disease pathology, triggering abnormal neurotoxic alpha-synuclein spread throughout the nervous system from the “critical point” of origin, and enabling a self-perpetuating degenerative process. The proposed hypothesis may have implications for the identification of new therapeutic targets, early prevention strategies, and the development of vascular and/or immune biomarkers. Full article

Background/Objectives: Necrotizing enterocolitis (NEC) is one of the most devastating gastrointestinal emergencies in premature neonates, with particularly high mortality among those requiring surgical intervention. Early identification of high-risk patients remains challenging. This study aimed to evaluate the prognostic value of complete blood count-derived inflammatory indices for predicting mortality in premature infants undergoing surgery for NEC. Methods: A total of 74 premature neonates with Bell stage II or III NEC who underwent surgical treatment between 2018 and 2023 were retrospectively analyzed. Preoperative and postoperative hematologic inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and platelet-to-neutrophil ratio (PNR), were recorded. Receiver operating characteristic (ROC) curve analysis was used to assess predictive performance. Variables with p < 0.10 in univariate analysis were entered into multivariate logistic regression models. Results: Overall mortality was 35.1%. Non-survivors had significantly lower gestational age and birth weight and a higher prevalence of advanced disease. Preoperatively, NLR was higher and PNR was lower in non-survivors. Postoperatively, NLR and C-reactive protein levels increased, while PNR showed a marked decline in infants who died. ROC analysis identified postoperative PNR as the strongest predictor of mortality, followed by preoperative SII and postoperative NLR. Multivariate analysis demonstrated that lower gestational age, advanced disease stage, and reduced postoperative PNR were independently associated factors for mortality. Conclusions: Postoperative reduction in platelet-to-neutrophil ratio appears to be a practical, inexpensive, and easily obtainable biomarker for early risk stratification in surgically treated NEC. Incorporating routine hematologic inflammatory indices into postoperative monitoring may support timely identification of high-risk infants and guide individualized clinical management in neonatal intensive care units. Full article

Infectious diseases present persistent and complex challenges to global public health, with conventional antibiotic therapies increasingly limited by antimicrobial resistance, microbiota disruption, and adverse effects. There is a critical need to explore complementary strategies that augment host defense mechanisms without exacerbating these limitations. Accumulating evidence underscores the integral role of the gut microbiota—a diverse microbial ecosystem within the gastrointestinal tract—in regulating systemic immunity and pathogen susceptibility. This review synthesizes recent advances from animal models to delineate the multi-faceted mechanisms by which commensal microbes and their metabolites confer protection against enteric and respiratory infections. Key processes include competitive exclusion for nutrients and ecological niches, production of antimicrobial compounds, reinforcement of intestinal barrier integrity, and orchestration of local and systemic immunity via gut–lung axes. We further discuss the potential of microbiota-targeted interventions to enhance treatment efficacy and patient outcomes. By integrating mechanistic insights with translational applications, this review aims to inform the rational design of next-generation anti-infective strategies grounded in microbial ecology and host immunobiology. Full article

Background/Objectives: Enteric glial cells (EGCs) are non-neuronal cells of the enteric nervous system that contribute to intestinal homeostasis through interactions with the intestinal epithelium, enteric neurons, and resident intestinal immune cells. The objective of the current study was to determine how exposure of EGCs to short-chain fatty acids (SCFAs) would affect the expression of growth factors and pro-inflammatory cytokines, products of EGCs with known effects on intestinal epithelial barrier integrity. Methods: An enteroglial cell line was treated with low- (1 mM) or high- (10 mM) dose sodium butyrate or sodium propionate for 8 to 24 h, after which mRNA and protein levels of glial cell line-derived neurotrophic factor (GDNF), transforming growth factor β-1 (TGFβ-1), tumor necrosis factor α (TNFα), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were measured using quantitative polymerase chain reaction assays and Western immunoblotting. Results: Only butyrate treatment for 8 and 24 h was associated with modest changes in GDNF mRNA. Neither SCFA elicited changes in TGFβ-1 mRNA. Despite this, high-dose butyrate and propionate were associated with reduced basal levels of TGFβ-1 protein as early as 12 h after treatment. Only butyrate was associated with a significant reduction in basal TNFα expression, which was present up to 24 h post-treatment. However, both butyrate (low- and high-dose) and propionate (high-dose only) elicited marked increases in IL-6 expression at all time points examined. Changes in cytokine mRNA levels were not mirrored at the protein level. Conclusions: SCFAs directly influence growth factor and cytokine expression in EGCs, but the functional implications of these changes in expression within the complicated milieux of the intestinal environment remain to be explored. Full article

The gut microbiota has emerged as a central regulator of the gut–brain axis, profoundly influencing neural, immune, and metabolic homeostasis. Increasing evidence indicates that disturbances in microbial composition and function contribute to the onset and progression of neurodegenerative diseases (NDs) through mechanisms involving neuroinflammation, oxidative stress, and impaired neurotransmission. Gut dysbiosis is characterized by a loss of microbial diversity, a reduction in beneficial commensals, and an enrichment of pro-inflammatory taxa. These shifts alter intestinal permeability and systemic immune tone, allowing microbial metabolites and immune mediators to affect central nervous system (CNS) integrity. Metabolites such as short-chain fatty acids (SCFAs), tryptophan derivatives, lipopolysaccharides (LPS), and trimethylamine N-oxide (TMAO) modulate blood–brain barrier (BBB) function, microglial activation, and neurotransmitter synthesis, linking intestinal imbalance to neuronal dysfunction and cognitive decline. Disruption of this gut–brain communication network promotes chronic inflammation and metabolic dysregulation, key features of neurodegenerative pathology. SCFA-producing and tryptophan-metabolizing bacteria appear to exert neuroprotective effects by modulating immune responses, epigenetic regulation, and neuronal resilience. The aim of this work was to comprehensively explore the current evidence on the bidirectional communication between the gut microbiota and the CNS, with a focus on identifying the principal molecular, immune, and metabolic mechanisms supported by the strongest and most consistent data. By integrating findings from recent human studies, this review sought to clarify how microbial composition and function influence neurochemical balance, immune activation, and BBB integrity, ultimately contributing to the onset and progression of neurodegenerative processes. Collectively, these findings position the gut microbiota as a dynamic interface between the enteric and CNS, capable of influencing neurodegenerative processes through immune and metabolic signaling. Full article