Search Results (529)

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

Transanal Irrigation (TAI) and Colon Hydrotherapy (CHT) represent emerging therapeutic options that may complement first-line interventions or serve as rescue treatments for chronic constipation and fecal incontinence. Their clinical utility depends on patient characteristics, specific therapeutic goals, device features, and probe type, as well as the procedural setting. This review presents the various pathophysiological contexts in which these techniques can be applied, analyzing their specific characteristics and potential pros and cons. Moreover, these interventions are also considered within a Psycho-Neuro-Endocrino-Immunological (PNEI) framework, given the potential influence of intestinal function and microbiota modulation on the bidirectional communication pathways linking the enteric nervous system, neuroendocrine regulation, immune activity, and global patient well-being. Since there is not yet enough scientific data on this topic, future research should prioritize randomized controlled trials comparing these techniques with other standard treatments (e.g., laxatives or dietary fiber) in defined patient populations. Longitudinal studies will also be essential to clarify long-term safety, potential effects on microbiota, and both risks and benefits. Standardization of technical procedures also remains a critical need, especially regarding professional competencies, operating parameters (e.g., instilled volumes and pressure ranges), and reproducible protocols. Moreover, future investigations should incorporate objective outcome measures, as colonic transit time, stool form and frequency, indices of inflammation or intestinal wall integrity, and changes to microbiome composition. In conclusion, TAI and CHT have the potential to serve as important interventions for the treatment and prevention of chronic constipation and intestinal dysbiosis, as well as their broader systemic correlates, in the setting of bio-integrated medicine. Full article

Particulate atmospheric pollution poses a global threat to human health. Metals enter the body through inhalation attached to these particles. Certain vulnerable groups are more susceptible to toxicity because of age, physiological changes, and chronic and metabolic diseases and also workers because of high and cumulative exposure to metals. A narrative review was conducted to examine the effects of key metals—arsenic, cadmium, chromium, copper, lead, mercury, manganese, nickel, vanadium, and zinc—on vulnerable populations, analyzing articles published over the past decade. Some of these metals are essential for humans; however, excessive levels are toxic. Other non-essential metals are highly toxic. Shared mechanisms of toxicity include competing with other minerals, oxidative stress and inflammation, and interacting with proteins and enzymes. Prenatal and childhood exposures are particularly concerning because they can interfere with neurodevelopment and have been associated with epigenetic changes that have long-term effects. Occupational exposure has been studied, but current exposure limits for specific metals appear dangerous, emphasizing the need to revise these standards. Older adults, pregnant women, and individuals with metabolic diseases are among the least studied groups in this review, underscoring the need for more research to understand these populations better and create effective public health policies. Full article

The enteric nervous system (ENS) constitutes a highly organized and intricate neuronal network comprising two principal plexuses: myenteric and submucosal. These plexuses consist of neurons and enteric glial cells (EGCs). Neurons ensure innervation throughout the intestinal wall, whereas EGCs, distributed within the mucosa, contribute to epithelial barrier integrity and modulation of local inflammatory responses. The ENS orchestrates essential gastrointestinal functions, including motility, secretion, absorption, vascular regulation, and immune interactions with gut microbiota. Under physiological conditions, intestinal homeostasis involves moderate generation of reactive oxygen species (ROS) through endogenous processes such as mitochondrial oxidative phosphorylation. Cellular antioxidant systems maintain redox equilibrium; however, excessive ROS production induces oxidative stress, promoting EGCs activation toward a reactive phenotype characterized by pro-inflammatory cytokine release. This disrupts neuron–glia communication, predisposing to enteric neuroinflammation and neurodegeneration. Obesity, associated with hyperglycemia, hyperlipidemia, and micronutrient deficiencies, enhances ROS generation and inflammatory cascades, thereby impairing ENS integrity. Nevertheless, non-pharmacological strategies—including synthetic and natural antioxidants, bioactive dietary compounds, probiotics, and prebiotics—attenuate oxidative and inflammatory damage. This review summarizes preclinical and clinical evidence elucidating the interplay among the ENS, obesity-induced oxidative stress, inflammation, and the modulatory effects of antioxidant interventions. Full article

Aflatoxin B₁ (AFB₁), a major metabolite of aflatoxin, is a highly toxic carcinogen. It frequently contaminates feed due to improper storage of feed ingredients such as corn and peanut meal, with the contamination risk further escalating alongside the increasing incorporation of plant-based proteins in feed formulations. Upon entering an organism, AFB₁ is metabolized into highly reactive derivatives, which trigger an oxidative stress-inflammation vicious cycle by binding to biological macromolecules, damaging cellular structures, activating apoptotic and inflammatory pathways, and inhibiting antioxidant systems. This cascade leads to stunted growth, impaired immunity, and multisystem dysfunction in animals. Long-term accumulation can also compromise reproductive function, induce carcinogenesis, and pose risks to human health through residues in the food chain. Tannins are natural polyphenolic compounds widely distributed in plants which exhibit significant antioxidant and anti-inflammatory activities and can effectively mitigate the toxicity of AFB₁. They can repair intestinal damage by increasing the activity of antioxidant enzymes and up-regulating the gene expression of intestinal tight junction proteins, regulate the balance of intestinal flora, and improve intestinal structure. Meanwhile, tannins can activate antioxidant signaling pathways, up-regulate the gene expression of antioxidant enzymes to enhance antioxidant capacity, exert anti-inflammatory effects by regulating inflammation-related signaling pathways, further reduce DNA damage, and decrease cell apoptosis and pyroptosis through such means as down-regulating the expression of pro-apoptotic genes. This review summarizes the main harm of AFB₁ to animals and the mitigating mechanisms of tannins, aiming to provide references for the resource development of tannins and healthy animal farming. Full article

Early-onset colorectal cancer (EOCRC) in people < 50 years of age has been rising globally, yet its causes remain unknown. Emerging evidence suggests that environmental factors, including exposure to micro-and nanoplastics (MNPs), may contribute to colorectal carcinogenesis. MNPs can enter the gastrointestinal tract through ingestion, translocate across the epithelial barrier via endocytosis or paracellular pathways, and interact directly with epithelial and immune cells. Once internalized, they may generate events associated with tumor initiation including oxidative stress, disruption of membrane integrity, pro-inflammatory signaling, and disruption of genomic and epigenomic stability. Patient-derived colorectal organoids offer a physiologically relevant and scalable 3D model that closely mimics the cellular architecture and genetic landscape of primary tumors. We highlight how organoid models can be leveraged to study the impact of MNPs on the key processes of inflammation, DNA damage, senescence, and epigenetic modifications. Furthermore, we discuss the application of organoid-based systems to model EOCRC driven by environmental exposures, including the integration of organoid platforms with high-throughput assays, omics profiling, and microfluidics to better capture MNP-induced pathogenic mechanisms. Altogether, colorectal organoids provide a powerful bridge between environmental plastic exposure and EOCRC etiology, offering a tractable platform to identify mechanistic pathways and potential biomarkers of early disease. Full article

Neonatal and weaning periods are the most challenging phases for enteric infections in dairy calves. While different approaches are used to minimize calf health issues, the neonatal diet remains the core approach to enhance pre- and post-weaning animal health and performance. This pilot study aimed to evaluate blood biomarkers of inflammation and fecal metabolites in calves supplemented with oligosaccharide mixture (OS) during the preweaning stage. Sixteen newborn Holstein dairy calves (eight females and eight males) were randomly assigned into two groups: control with no supplementation, or treatment with 50 g/day of OS added to the pasteurized waste milk feeding. Both control and OS-treated calves were fed pasteurized waste milk during the preweaning period and weaned at seven weeks of age. Blood and fecal samples were collected weekly. Fecal fatty acid metabolites were downregulated in treated calves compared to control calves (p ≤ 0.05). Markers of inflammation (i.e., haptoglobin) or liver response (i.e., albumin, paraoxonase) did not differ between groups (p > 0.05). Overall, these findings suggest that dietary intervention with oligosaccharides can affect host metabolic pathways. Full article

Crohn’s disease (CD) remains a highly complex disorder, and the progress of preclinical gene therapy for CD has been constrained by several significant challenges. These include the identification of optimal therapeutic gene targets, the difficulty of targeting therapy-resistant cells within a chronic inflammatory microenvironment, particularly in the enteric nervous system (ENS), and the lack of robust animal models that faithfully recapitulate human pathology, as classical models largely rely on toxin-induced colitis. This review synthesizes major preclinical studies on gene therapy for CD and related inflammatory bowel diseases (IBD). We critically assess the rationale and biodistribution data for different vector platforms, considering vector type, promoter, and route of administration, in the ileum and colon of both rodent and non-human primate models. Special attention is given to strategies targeting the ENS. Finally, we explore the putative therapeutic aims of these approaches, including direct attenuation of intestinal inflammation and prevention of postoperative recurrence of CD via local intraoperative gene delivery. Although most data derive from chemical colitis models, this review establishes a foundational framework to inform translational research in gene therapy for CD and other IBDs. Full article

Bone is a structurally complex and dynamic tissue that plays a crucial role in mobility and skeletal stability. However, conditions such as osteoporosis, osteoarthritis, trauma-induced fractures, infections, and malignancies often necessitate the use of orthopedic and dental implants. Despite significant progress in implant biomaterials, challenges such as bacterial infection, inflammation, and loosening continue to compromise implant longevity, frequently leading to revision surgeries and extended recovery times. Smart coatings have emerged as a next-generation solution to these problems by providing on-demand, localized therapeutic responses to microenvironmental changes around implants and promoting bone regeneration. Such coatings can minimize antibiotic resistance by enabling controlled, stimulus-triggered drug release. Although the idea of using pH-sensitivity as a tool to make smart coatings is not a new thought, there are no options currently good enough to enter clinical studies. This review provides a comprehensive overview of recent advances in pH-sensitive polymers, hybrid composites, porous architectures, and bioactive linkers designed to dynamically respond to pathological pH variations at implant sites. By investigating the mechanisms of action, antibacterial and anti-inflammatory effects, and roles in bone regeneration, it is shown that the ability to provide time-dependent drug release for both short-term and long-term infections, as well as keeping the environment welcoming to the bone cell growth and replacement, is not an easy goal to reach, even with a fully biocompatable, non-toxic, and semi-biodegradable (one that releases the drug, but does not fade away) coating material compound. Reviewing all available options, including their functions and failures, finally, emerging trends, translational barriers, and future opportunities for clinical implementation are highlighted, underscoring the transformative potential of bioresponsive coatings in orthopedic and dental implant technologies. Full article

Inflammatory bowel disease (IBD) is a chronic condition whose pathogenesis is not entirely clear. Impaired immune regulation has been hypothesized as the mechanism responsible for the abnormal response of adoptive immunity to enteric microbial antigens. Regulatory T cells (Tregs) have been regarded as the crucial element of immune regulation, since the discovery that humans lacking Tregs due to mutation of FOXP3 develop autoimmune disorders, including severe bowel inflammation. The existing publications concerning T regulatory cells in human IBD have been reviewed, and current evidence does not clearly indicate quantitative disturbances or functional defects of Tregs in human inflammatory bowel disease. The possible mechanisms explaining immunoregulatory failure in IBD have been summarized. So far, only one clinical trial with Tregs infusion has been completed, and its results do not provide sufficient data on the efficacy or safety of Tregs-based therapies in IBD. It will probably be difficult to implement them in clinical practice in the near future. Full article

Methamphetamine (MA) abuse has emerged as a multisystem insult driving cardiovascular and neurovascular consequences. Methamphetamine-associated cardiomyopathy (MACM) remains an underrecognized cause of cardioembolic stroke through left ventricular thrombus (LVT) formation. MA-induced gut dysbiosis and enteric neural disruption exacerbate systemic inflammation and autonomic imbalance, resulting in broader dysregulation of the brain–heart–gut axis. This study aimed to synthesize contemporary evidence on chronic MA exposure and its role in LVT formation, stroke pathogenesis, diagnostic approaches, and anticoagulation management. We conducted a focused narrative review of PubMed- and Scopus-indexed literature (1990–2025) addressing cardiovascular, neurovascular, and gut-mediated consequences of chronic MA exposure. Observational cohorts and case reports were integrated to characterize pathophysiology, imaging approaches, and therapeutic considerations, supplemented by a representative clinical case. Chronic MA exposure mediates persistent catecholamine excess, myocardial fibrosis, ventricular dysfunction, and a prothrombotic milieu. Gut dysbiosis-related inflammation and autonomic dysregulation further promote intracardiac stasis. Affected individuals are typically young men with severe systolic dysfunction (left ventricular ejection fraction 20–30%), with a substantial proportion demonstrating apical or mural LVT on systematic imaging. Case-level evidence highlights a broader systemic embolic burden, involving the limbs, kidneys, and aorta. Echocardiography remains the first-line screening method, while cardiac CT and MRI offer greater sensitivity for thrombus detection. Anticoagulation is challenged by bleeding risk, inconsistent adherence, and the absence of standardized protocols. MACM represents a critical and underrecognized etiology of cardioembolic stroke in young adults. Early recognition of brain–heart–gut axis disruption, systematic cardiac imaging, and individualized anticoagulation are crucial for preventing emboli. Prospective registries and standardized imaging-guided treatment strategies are needed to improve outcomes in this high-risk population. Full article

Ultra-processed foods (UPFs), industrial formulations rich in refined substrates and additives, have been increasingly examined as plausible contributors to gut dysbiosis and mucosal inflammation relevant to inflammatory bowel disease (IBD). This narrative review synthesizes epidemiological, mechanistic, and interventional evidence on UPF intake and IBD based on a structured literature search from 2010 to 2025. Large-scale prospective cohorts consistently associate higher UPF intake with increased risk of Crohn’s disease (CD), whereas findings for ulcerative colitis (UC) remain weaker or inconsistent. Among individuals with established IBD, observational data suggest that greater UPF consumption correlates with higher disease activity and relapse, although potential confounding and reverse causation must be considered. Preclinical studies demonstrate that specific UPF constituents—including emulsifiers, carrageenan, maltodextrin, microparticles, and excess dietary salt—can disrupt epithelial barrier integrity, alter the gut microbiota, and activate immune pathways, providing biological plausibility while underscoring translational gaps. Interventional evidence, particularly for exclusive enteral nutrition and the Crohn’s Disease Exclusion Diet, suggests clinical benefit from reducing UPFs or selected additives, mainly in CD, though data in adults and UC remain limited. Overall, current evidence indicates that dietary strategies to limit UPF exposure may represent a promising and modifiable component of IBD management. Future research should prioritize standardized exposure assessment, mechanism-based human trials, and personalized nutrition approaches to refine clinical applicability. Full article

Pelvic inflammatory disease (PID), although traditionally viewed as a sexually transmitted infection (STI), can also result from non-sexually transmitted microorganisms that display distinct epidemiologic and clinical characteristics. Unlike STI-related PID, these infections are less influenced by sexual behavior, often show a bimodal age distribution, and are linked to bacterial vaginosis (BV)-associated dysbiosis, iatrogenic uterine procedures, postpartum states, or inadequate access to timely screening and care. Non-STI-related PID is usually polymicrobial, predominantly involving BV-associated vaginal, enteric, or urinary commensals that ascend into the upper genital tract, while respiratory tract organisms, mycobacteria, and biofilm-associated pathogens may also play a role. Pathophysiological mechanisms include disruption of the endocervical barrier, mucus degradation, biofilm formation, hematogenous or iatrogenic seeding, and chronic cytokine-mediated inflammation and fibrosis. Clinical manifestations range from asymptomatic/subclinical disease to acute pelvic pain and tubo-ovarian abscess (TOA) and can progress to systemic infection and sepsis. Diagnosing non-STI PID is challenging due to nonspecific symptoms, negative STI tests, and inconclusive imaging findings, while management relies on broad-spectrum antimicrobials with surgery as needed. Given these complexities, this review aims to synthesize current knowledge on non-STI-related PID, clarify key considerations for its diagnosis, management, and prevention, and outline future perspectives to improve clinical outcomes. Full article

Accurate and timely identification of enteric pathogens is crucial for guiding treatment in hospitalized patients with acute diarrhea. Conventional stool testing often lacks sensitivity, whereas multiplex PCR diagnostics offer rapid, comprehensive pathogen detection. This retrospective multicenter study included 267 adult inpatients with acute diarrhea from two hospitals. Patients underwent either traditional stool diagnostics (n = 146) or multiplex PCR testing combined with stool culture (n = 121). Clinical data, diagnostic yields, antibiotic use, and clinical outcomes were analyzed. The multiplex PCR group demonstrated a significantly higher diagnostic yield than traditional testing (77.7% vs. 41.1%, p < 0.001), detecting more mixed infections (34.7%) and a broader range of pathogens, including Campylobacter, viruses, and parasites. PCR positivity correlated independently with bloody diarrhea (OR 16.5; 95% CI: 1.81–150.26) and dehydration (OR 7.05; 95% CI: 1.40–35.45). PCR testing reduced inappropriate antibiotic use (OR 0.30; p < 0.001), shortened antibiotic duration post-result (median 5 vs. 7 days; p < 0.0001), and increased antibiotic adjustments (42.1% vs. 27.4%; p = 0.011) and discontinuation (12.4% vs. 3.7%; p = 0.033). The PCR group had more ICU admissions (20.7% vs. 7.1%, p = 0.001) and longer hospital stays (median 10 vs. 6 days, p < 0.0001), reflecting more severe illness. Liver cirrhosis, comorbidity burden, and systemic inflammation predicted worse outcomes. Multiplex PCR enhances pathogen detection and promotes antibiotic stewardship in hospitalized patients with diarrhea. Rapid results support earlier, targeted clinical decisions, particularly in patients with complex comorbidities or severe presentations. Full article

Background/Objectives: Sepsis-associated liver injury (SALI) is a critical and often early complication of sepsis, defined by distinct hyper-inflammatory and immunosuppressive phases that shape patient phenotypes. Methods: Characterizing these phases establishes a foundation for immunomodulation strategies tailored to individual immune responses, as discussed subsequently. Results: The initial inflammatory response activates pathways such as NF-κB and the NLRP3 inflammasome, leading to a cytokine storm that damages hepatocytes and is frequently associated with higher SOFA scores and a higher risk of 28-day mortality. Kupffer cells and infiltrating neutrophils exacerbate hepatic injury by releasing proinflammatory cytokines and reactive oxygen species, thereby causing cellular damage and prolonging ICU stays. During the subsequent immunosuppressive phase, impaired infection control and tissue repair can result in recurrent hospital-acquired infections and a poorer prognosis. Concurrently, hepatocytes undergo significant metabolic disturbances, notably impaired fatty acid oxidation due to downregulation of transcription factors such as PPARα and HNF4α. This metabolic alteration corresponds with worsening liver function tests, which may reflect the severity of liver failure in clinical practice. Mitochondrial dysfunction, driven by oxidative stress and defective autophagic quality control, impairs cellular energy production and induces hepatocyte death, which is closely linked to declining liver function and increased mortality. The gut-liver axis plays a central role in SALI pathogenesis, as sepsis-induced gut dysbiosis and increased intestinal permeability allow bacterial products, including lipopolysaccharides, to enter the portal circulation and further inflame the liver. This process is associated with sepsis-related liver failure and greater reliance on vasopressor support. Protective microbial metabolites, such as indole-3-propionic acid (IPA), decrease significantly during sepsis, removing key anti-inflammatory signals and potentially prolonging recovery. Clinically, SALI most commonly presents as septic cholestasis with elevated bilirubin and mild transaminase changes, although conventional liver function tests are insufficiently sensitive for early detection. Novel biomarkers, including protein panels and non-coding RNAs, as well as dynamic liver function tests such as LiMAx (currently in phase II diagnostics) and ICG-PDR, offer promise for improved diagnosis and prognostication. Specifying the developmental stage of these biomarkers, such as identifying LiMAx as phase II, informs investment priorities and translational readiness. Current management is primarily supportive, emphasizing infection control and organ support. Investigational therapies include immunomodulation tailored to immune phenotypes, metabolic and mitochondrial-targeted agents such as pemafibrate and dichloroacetate, and interventions to restore gut microbiota balance, including probiotics and fecal microbiota transplantation. However, translational challenges remain due to limitations of animal models and patient heterogeneity. Conclusion: Future research should focus on developing representative models, validating biomarkers, and conducting clinical trials to enable personalized therapies that modulate inflammation, restore metabolism, and repair the gut-liver axis, with the goal of improving outcomes in SALI. Full article