Search Results (1,424)

Globally, Parkinson’s disease (PD) is the neurodegenerative condition with the most rapidly increasing prevalence, and a growing body of evidence associates its pathology with impairments in the gut–brain axis. Traditionally viewed as a disease marked by the loss of dopaminergic neurons, emerging evidence emphasizes that chronic neuroinflammation is a driver of neurodegeneration, with gut-originating inflammation playing a crucial role. Increased intestinal permeability, often called “leaky gut,” allows harmful substances, toxins, and misfolded α-synuclein into the systemic circulation, potentially exacerbating neuroinflammation and spreading α-synuclein pathology to the brain through the vagus nerve or compromised blood–brain barrier (BBB). This review synthesizes current insights into the relationship between gut health and PD, emphasizing the importance of gut permeability in disrupting intestinal barrier function. This paper highlights innovative therapeutic approaches, particularly personalized therapies involving gut microbiome engineering, as promising strategies for restoring gut integrity and improving neurological outcomes. Modulating specific gut bacteria to enhance the synthesis of certain metabolites, notably short-chain fatty acids (SCFAs), represents a promising strategy for reducing inflammatory responses and decelerating neurodegeneration in Parkinson’s disease. Full article

Microplastics (MPs) are plastic particles smaller than 5 mm that accumulate in ecosystems and can cause toxicity in organisms by affecting multiple biological processes. This study investigates the effects of poly(methyl methacrylate) microplastic microspheres (MPs, 200 µm diameter) on Caenorhabditis elegans, a widely used model in ecotoxicology. Nematodes were exposed to MPs at concentrations of 0.01, 0.1, 1, and 10 mg/mL, and various toxicological endpoints were assessed. The uptake of MPs was evaluated by µFT-IR analysis. The results indicate that MPs induce a concentration-dependent reduction in body length and alterations in the reproduction rate. Lifespan was also significantly reduced, with a 20% decrease at the highest concentration. Intestinal permeability assays revealed disruption of gut integrity at higher concentrations, and oxidative stress analysis showed a 1.8-fold increase in reactive oxygen species (ROS) levels at 10 mg/mL. Gene expression analysis via real-time qPCR indicated the upregulation of genes involved in oxidative stress and in DNA repair mechanisms. Additionally, the longevity-related transcription factors daf-16 and skn-1 were modulated, suggesting an adaptive stress response. These findings suggest that MPs impair growth, reproduction, and oxidative stress response in C. elegans, emphasizing the potential risks associated with microplastic exposure. Full article

Ochratoxin A (OTA) is a widespread foodborne mycotoxin that poses significant risks to both human and animal health. Upon ingestion, the gastrointestinal tract (GIT) becomes the main site of exposure, where OTA interacts directly with the intestinal epithelium and resident microbiota. Research indicates that OTA disrupts the integrity of the intestinal barrier and alters its permeability. Moreover, OTA undergoes transport and partial metabolism within the intestine before being excreted. Detoxification pathways for OTA include enzymatic degradation and adsorption by microorganisms. Notably, OTA has profound toxic effects on the gut ecosystem; it can alter the relative abundance of bacterial taxa by reducing beneficial populations and promoting opportunistic or pathogenic strains. These changes contribute to an imbalance in the microbiota, impairing host metabolic and immune functions. This dysbiosis is characterized by disrupted microbial homeostasis and impaired communication between the host and its gut microbiome. This review highlights the dual role of the intestine as both a target and a modulator of OTA toxicity. It emphasizes the importance of gut microbiota in mediating the toxicological outcomes of OTA and explores microbiome-based strategies as potential avenues for detoxification. Full article

Background: The gut-liver axis is essential for maintaining liver physiology, with the gut microbiota playing a central role in this bidirectional communication. Recent studies have identified microbiota-derived extracellular vesicles (EVs) as key mediators of inter-organ signaling. This study explored the impact of EVs from two beneficial Escherichia coli strains, the probiotic EcN and the commensal EcoR12, on hepatic metabolism and oxidative stress in healthy neonatal rats. Methods: EVs were administered orally during the first 16 days of life, and blood and liver samples were collected on days 8 and 16. Results: The results demonstrated that EVs significantly reduced intestinal permeability, as evidenced by decreased plasma zonulin levels. In the liver, EVs enhanced redox homeostasis by downregulating CYP2E1 and upregulating key antioxidant genes (SOD1, CAT, GPX). Furthermore, the treatment shifted liver metabolism toward an anti-lipogenic profile by inducing fatty acid oxidation genes (PPARA, CPT1A) and suppressing genes involved in de novo lipogenesis (SREBP1C, ACC1, FASN, CNR1). Importantly, markers of hepatic inflammation remained unchanged, indicating the safety of the intervention. In vitro experiments using human HepG2 cells supported these findings, further validating the antioxidant and metabolic effects of the EVs. Conclusions: Our results underscore the role of microbiota-derived EVs as important mediators of hepatic metabolic programming in healthy individuals via the gut-liver axis and highlight their potential as therapeutic postbiotic agents for management of fatty liver diseases. Full article

Curcumin (CUR) is a bioactive compound with well-documented therapeutic potential in diverse pathological conditions, encompassing intestinal disorders—most notably colonic cancer—as well as extra-intestinal malignancies such as hepatic, breast, and renal tumors. However, the therapeutic efficacy of CUR is severely constrained by its poor aqueous solubility, chemical instability, and consequent low systemic bioavailability. Nano-scaled carriers (nanocurcumin) enhance CUR solubility and membrane permeability through their reduced dimensions and/or specific interactions with membrane constituents. Nevertheless, conventional nanocurcumin formulations, such as unmodified liposomes, nanocapsules, nanogels, and nanofibers, continue to accumulate substantially in non-target tissues because of their lack of disease-specific tropism. This review focuses on the most recent advances in active targeting strategies for nanocurcumin, specifically receptor-mediated cellular targeting for extra-intestinal pathologies and colon-specific ligand-directed delivery for intestinal disorders. Current methodologies for validating the efficacy of engineered nanocurcumin formulations are critically reviewed, and the prevailing limitations alongside prospective future applications of nanocurcumin are delineated and discussed. Full article

Psychological stress is deeply involved in the pathophysiology of gastrointestinal diseases. We investigated the effect of psychological stress on the small-intestinal environment, including gut flora, immune system, and mucosal integrity in mice subjected to chronic social defeat stress (CSDS). CSDS mice were established by exposing a C57BL/6N mouse to an ICR aggressor mouse. Stool samples were obtained to investigate its properties and the gut microbiome profile. Using small-intestinal tissues, the expression of cytokines, antimicrobial peptides, and tight junction proteins (TJPs) were examined by real-time RT-PCR and immunohistochemistry. Small-intestinal permeability was evaluated by transepithelial electrical resistance assay. For stool properties, mean Bristol scale score and fecal water content were significantly lower in the CSDS group. Pseudomonadota and Patescibacteria were significantly more abundant in the stools from CSDS mice. Among TJPs and antimicrobial peptides, the expression of Occludin, Claudin-4, and Regenerating gene IIIγ was significantly decreased in the small intestine epithelium of CSDS mice. The small-intestinal permeability was significantly increased in CSDS mice. Lipopolysaccharide immunoreactivity, the number of macrophages, and proinflammatory IL-1β expression were significantly increased in the small intestine of CSDS mice. These findings suggest that psychological stress is associated with mucosal barrier dysfunction and microinflammation in small-intestinal tissues. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the pathological aggregation of α-synuclein (α-syn), the loss of dopaminergic neurons, and the appearance of both motor and non-motor symptoms. Emerging evidence suggests a bidirectional influence of the microbiota–gut–brain axis in PD pathogenesis, where gut dysbiosis contributes to increased intestinal barrier permeability, immune activation, chronic inflammation, oxidative stress, α-syn misfolding, and neurotransmitter imbalance. These findings are increasing interest in probiotics as microbiota-targeted interventions that restore intestinal and systemic homeostasis. Lactiplantibacillus plantarum, a probiotic species with remarkable environmental adaptability and genomic plasticity, has emerged as a promising candidate for PD management. Preclinical studies demonstrate that specific Lpb. plantarum strains, such as PS128 or CCFM405, can beneficially modulate gut microbial communities, reinforce barrier integrity, regulate bile acid metabolism, attenuate neuroinflammatory responses, and improve motor deficits in PD-like mice. In addition, Lpb. plantarum DP189 or SG5 interventions can significantly reduce α-syn aggregation in the brain via suppression of oxidative stress, modulation of neuroinflammatory responses, and activation of neurotrophic factors. Recent evidence even suggests that Lpb. plantarum-derived extracellular vesicles may possess anti-PD activity by influencing host gene expression, neuronal function, and immune modulation. Although robust clinical data are still limited, preliminary clinical trials indicate that supplementation with PS128 or certain Lpb. plantarum-contained consortiums can alleviate constipation, improve gastrointestinal function, reduce systemic inflammation, and even ameliorate motor symptoms when used alongside standard dopaminergic therapies. In this review, we provide an integrated overview of preclinical, clinical, and mechanistic insights, and evaluate the translational potential of Lpb. plantarum as a safe and diet-based strategy to target the microbiota-gut–brain axis in PD. Full article

Chronic stress induces mood disturbances, disrupts gut barrier function, and promotes low-grade systemic inflammation. This study assessed the therapeutic effects of atomoxetine (ATX), escitalopram (ESC), cannabidiol (CBD), and CBD-loaded lipid nanoparticles (CBD/LNP) in male rats exposed to repeated restraint stress. Stressed rats exhibited a 2.03-fold increase in interleukin-6 and a 1.89-fold increase in TNF-α, a 1.20-fold decrease in brain-derived neurotrophic factor, a 1.36-fold decrease in osteocalcin, accompanied by alterations in gut metabolites, particularly short-chain fatty acids (SCFAs; from 155.3 to 94.83 μmol/L), polyamines (from 273.6 to 192.4 μmol/L), and bile acids (BAs; from 21.19 to 14.53 μmol/L), compared with the control group. Protein analysis revealed gut barrier disruption and microglial/macrophage activation, accompanied by reduced synaptic plasticity. ATX improved gut permeability and reduced glial activation but did not restore osteocalcin. ESC provided neuroimmune benefits with limited and BA gut restoration and modulated the gut–brain axis and improved anxiety-like behaviors, partly by altering gut microbiota and metabolites. CBD and CBD/LNP treatment restored intestinal barrier function, as indicated by intestinal permeability in the range of 1.15–1.61-fold. These treatments also normalized bile acids (1.0–1.38-fold) and osteocalcin (1.0–1.28-fold) and significantly reduced glial activation (0.63–1.12-fold) as opposed to the non-treated stressed group. All treatments were found to be effective in correcting SCFA and polyamine levels. Histological analysis confirmed that CBD/LNP, ATX, and ESC ameliorated tissue alterations. These findings highlight CBD/LNP as a promising intervention for stress-induced gut–brain–bone axis disruption, supporting its potential as a therapeutic alternative through modulation of microbiota-driven gut–brain communication in stress-associated disorders. Full article

Deoxynivalenol (DON), a mycotoxin from Fusarium that contaminates cereals, can also induce intestinal injury. However, the mechanisms underlying DON-induced jejunal barrier injury remain unclear. This study demonstrates that shikimic acid (SA) alleviates DON-induced jejunal barrier damage and dysbiosis via antioxidant pathways. Fifty 5-week-aged male KM mice were divided into control (CON), model (MOD, 2.4 mg/kg bw DON), and SA-treated groups (LDG/MDG/HDG: 25/50/100 mg/kg bw SA + DON). After SA treatment, notably MDG, reversed DON-induced weight loss and jejunal hyperemia; ameliorated villus atrophy, crypt deepening and goblet cell loss, increasing villus/crypt ratio; reduced gut permeability markers (D-LA/DAO) and pro-inflammatory cytokines (TNF-α/IL-6/IL-1β); and dose-dependently upregulated tight junction proteins (ZO-1/Occludin/Claudin1). Mechanistically, SA activated the Nrf2/HO-1/NQO1 pathway, elevating antioxidants (GSH/SOD/AOC) while reducing MDA, with MDG showing optimal efficacy. 16S rRNA sequencing revealed MDG counteracted DON-induced dysbiosis by enriching beneficial bacteria (e.g., Bacteroidota at phylum level; Muribaculaceae at family level) and suppressing pathogens (Staphylococcaceae) (LDA score > 4.0). Thus, SA mitigates DON toxicity via Nrf2-mediated barrier restoration, anti-inflammation, and microbiota modulation. This research provides new insights for the further development of Shikimic Acid and the treatment of DON-induced jejunal barrier injury. Full article

Secondary liver injury (SLI) is the most common complication in the development of inflammatory bowel disease (IBD), and it is susceptible to environmental factors, including diet patterns. As a food-brightening agent, titanium dioxide nanoparticles (TiO₂ NPs) are inevitably consumed by IBD patients. Currently, there are a few studies on TiO₂ NPs exposure to SLI in colitis mice. In this study, a SLI model was built using dextran sodium sulfate (DSS) free-drinking for 7 days after pre-exposure to TiO₂ NPs. The changes in the pathological results and liver function indicators suggested that high-dose TiO₂ NPs only exhibited a slight injury in the liver. With further analysis, we found that pre-exposure to high-dose TiO₂ NPs in mice with SLI led to an increase in intestinal permeability and hepatic LPS content, along with increased inflammatory cytokines and an anti-oxidative system imbalance. Subsequently, accumulated LPS and ROS overproduction activated the NOD-like receptor family pyrin-containing 3 (NLRP3) inflammasome, inducing hepatic cell pyroptosis. To provide compelling evidence, NLRP3 gene-deficient mice were used, and the results showed that the absence of NLRP3 improved liver function, alleviated hepatic inflammation, and reduced hepatic oxidative injury in SLI mice with TiO₂ NPs exposure. In summary, these results confirmed the critical role of the NLRP3 inflammasome in the TiO₂ NP-aggravated progression of SLI. Our study provided a comprehensive evaluation of foodborne nanoparticles on IBD complications, hoping that more studies can focus on IBD complications affected by environmental factors. Full article

Background/Objectives: HIV infection has been associated with an increased incidence of non-communicable comorbidities, including metabolic disorders. This phenomenon has been linked to gut microbiota dysbiosis, which involves not only changes in bacterial composition but also functional alterations in metabolite production. The objective of this study was to describe the impact of intestinal microbial metabolomics on the development of type 2 diabetes in people living with HIV. Methods: This study provides a narrative synthesis of current evidence addressing the role of gut microbiota-derived metabolites in immunometabolic regulation and their implications in HIV-associated type 2 diabetes. Results: Microbial metabolites play a fundamental role in regulating key physiological processes such as intestinal permeability, systemic immune activation, and glucose metabolism. Compounds such as short-chain fatty acids, tryptophan catabolites, secondary bile acids, trimethylamine N-oxide, and imidazole propionate have been shown to significantly influence immunometabolic balance. In people living with HIV, these microbial products may exert diverse effects depending on their chemical nature and the molecular pathways they activate in peripheral tissues. The interaction between dysbiosis, chronic low-grade inflammation, and HIV-associated metabolic disturbances may contribute to the early onset of type 2 diabetes beyond traditional risk factors. Conclusions: Recognizing the role of microbial metabolites in the context of HIV infection is essential to broaden our pathophysiological understanding of associated metabolic comorbidities. It also opens opportunities to develop more comprehensive diagnostic and therapeutic strategies that include modulation of the gut microbiota and its metabolic activity for the prevention and management of type 2 diabetes in this population. Full article

Over the past decade, significant attention has been directed toward understanding the role of the gut microbiome in health and disease. The gut microbiota, comprising a complex and diverse community of microorganisms, has been linked to numerous conditions, including metabolic disorders, gastrointestinal diseases, and inflammatory or autoimmune conditions. Recently, a growing body of evidence has revealed a compelling relationship between gut microbiota composition and musculoskeletal injury recovery, highlighting its potential as a novel therapeutic target. Musculoskeletal injuries, including fractures, post-traumatic osteoarthritis, and tendon or ligament injuries, commonly lead to changes in the community structure of the gut microbiota, intestinal permeability, and systemic inflammation, processes known to negatively influence tissue repair. Preclinical studies demonstrate that microbiota-targeted interventions, such as probiotics, prebiotics, and fecal microbiota transplantation, effectively restore gut barrier integrity, modulate inflammation, and normalize gut-derived metabolite profiles. Despite these promising findings, critical gaps remain in translating these effects into clinical practice, particularly regarding the mechanisms linking specific microbiota changes to improved musculoskeletal healing outcomes. Future research incorporating rigorous clinical trials, multi-omics analyses, and advanced predictive tools, including artificial intelligence and microbiome-informed digital twins, is urgently needed to fully harness the therapeutic potential of microbiome-based interventions in musculoskeletal injury recovery. This narrative review provides insights into our evolving understanding of the relationship between the gut microbiota and musculoskeletal injury and explores the potential of gut microbiota-targeted therapies for improved healing outcomes. Full article

Hyaluronic acid (HA), which is present in various foods, has been the subject of various claims about its ability to relieve dry skin. In this study, the intestinal absorption of hyaluronic acid tetrasaccharide (HA4) and its ability to protect the skin from UV after oral administration were compared with those of high-molecular-weight HA. Intestinal absorption was evaluated by the Caco-2 cell monolayer mem-brane permeability assay. HA4 permeated the Caco-2 monolayer, reaching 2.67 µg/cm² after 120 min, whereas HA did not. HA or HA4 was orally administered to UVB-irradiated mice, and the effects were evaluated using transepidermal water loss (TEWL), water content of the stratum corneum (SC), and epidermal thickness. HA4 permeated the Caco-2 monolayer. On day 26, TEWL significantly increased by 17.5 ± 3.1 g/m²/h in the Control group but only 8.0 ± 1.7 g/m²/h in the HA4 group compared to the Normal group, but no significant difference was observed. Water content of SC decreased by 25.7 ± 1.5 arbitrary units (a.u.) in the Control group; the decrease was attenuated in the HA4 group (17.5 ± 0.7 a.u.) (p < 0.05 vs. Control). On day 28, epidermal thickness reached 69.5 ± 10.8 µm in the Control group and was significantly lower in the HA4 group (43.5 ± 5.1 µm) (p < 0.01 vs. Control). These findings indicate that orally administered HA4 is efficiently absorbed and significantly attenuates UVB-induced skin barrier impairment, suggesting its promise as a functional food ingredient for improving dry skin. Full article

Background/Objectives: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition often accompanied by gastrointestinal (GI) symptoms and gut microbiota imbalances. The microbiota–gut–brain (MGB) axis is a bidirectional communication network linking gut microbes, the GI system, and the central nervous system (CNS). This narrative review explores the role of the MGB axis in ASD pathophysiology, focusing on communication pathways, neurodevelopmental implications, gut microbiota alteration, GI dysfunction, and emerging therapeutics. Methods: A narrative review methodology was employed. We searched major scientific databases including PubMed, Scopus, and Google Scholar for research on MGB axis mechanisms, gut microbiota composition in ASD, dysbiosis, leaky gut, immune activation, GI disorders, and intervention (probiotics, prebiotics, fecal microbiota transplantation (FMT), antibiotics and diet). Key findings from recent human, animal and in vitro studies were synthesized thematically, emphasizing mechanistic insights and therapeutic outcomes. Original references from the initial manuscript draft were retained and supplemented for comprehensiveness and accuracy. Results: The MGB axis involves neuroanatomical, neuroendocrine, immunological, and metabolic pathways that enable microbes to influence brain development and function. Individuals with ASD commonly exhibit gut dysbiosis characterized by reduced microbial diversity (notably lower Bifidobacterium and Firmicutes) and overpresentation of potentially pathogenic taxa (e.g., Clostridia, Desulfovibrio, Enterobacteriaceae). Dysbiosis is associated with increased intestinal permeability (“leaky gut”) and newly activated and altered microbial metabolite profiles, such as short-chain fatty acids (SCFAs) and lipopolysaccharides (LPSs). Functional gastrointestinal disorders (FGIDs) are prevalent in ASD, linking gut–brain axis dysfunction to behavioral severity. Therapeutically, probiotics and prebiotics can restore eubiosis, fortify the gut barrier, and reduce neuroinflammation, showing modest improvements in GI and behavioral symptoms. FMT and Microbiota Transfer Therapy (MTT) have yielded promising results in open label trials, improving GI function and some ASD behaviors. Antibiotic interventions (e.g., vancomycin) have been found to temporarily alleviate ASD symptoms associated with Clostridiales overgrowth, while nutritional strategies (high-fiber, gluten-free, or ketogenic diets) may modulate the microbiome and influence outcomes. Conclusions: Accumulating evidence implicates the MGB axis in ASD pathogenesis. Gut microbiota dysbiosis and the related GI pathology may exacerbate neurodevelopmental and behavioral symptoms via immune, endocrine and neural routes. Interventions targeting the gut ecosystem, through diet modification, probiotics, symbiotics, or microbiota transplants, offer therapeutic promise. However, heterogeneity in findings underscores the need for rigorous, large-scale studies to clarify causal relationships and evaluate long-term efficacy and safety. Understanding MGB axis mechanisms in ASD could pave the way for novel adjunctive treatments to improve the quality of life for individuals with ASD. Full article

Inflammatory bowel disease (IBD) is an autoimmune condition with an increasing incidence worldwide, which manifests in two pathological forms: Crohn’s disease (CD) or ulcerative colitis (UC). Both cause chronic inflammation of the digestive tract, although they can present different locations and with different symptoms. To date, the pathogenesis of IBD remains unclear. One of the major complications of these diseases is colorectal cancer. Several studies have reported a correlation between chronic intestinal inflammation and an increased risk of malignancy. Persistent inflammation damages the intestinal mucosa and epithelial wall, altering gut permeability and the local microenvironment. Moreover, the heightened activity of the immune system leads to an increased production of reactive oxygen and nitrogen species (ROS and RNS), increasing the risk of DNA mutation and cell transformation. In addition, some current therapies used to treat IBD and induce remission may contribute to carcinogenesis or impair immune surveillance due to their immunosuppressive activity. The management of cancer risk for IBD patients remains a challenge, and existing screening methods are often invasive (endoscopies, biopsies), resulting in low patient compliance. To address this unmet clinical need, researchers have started using proteomics to identify novel biomarkers that could predict cancer risk in IBD patients in a non-invasive manner. This review aims to examine the current state of knowledge regarding the correlation between IBD and cancer, with a special focus on the biomarkers discovered through proteomic approaches, and their potential application in routine clinical screening. In our view, proteomics represents a powerful and rapidly evolving strategy for biomarker discovery, with the potential to complement or even replace invasive procedures. Its future clinical impact will rely on translating current research advances into robust and accessible diagnostic tools. Full article