Search Results (236)

Background/Objectives: Gut dysbiosis in Chronic Fatigue Syndrome (CFS) drives low-grade inflammation and shifts tryptophan metabolism toward neurotoxic pathways. The causal link between bacterial translocation, kynurenine pathway dysregulation, and symptom severity remains under-defined. We evaluated the impact of a high-concentration multi-strain probiotic on the “gut-kynurenine axis” and clinical status in CFS patients with co-morbid IBS-U and confirmed dysbiosis. Methods: Forty female patients with confirmed dysbiosis (GA-map™ Dysbiosis Index > 2) received the CDS22 formula (450 billion CFU/day) for 12 weeks. We compared urinary tryptophan metabolite profiles (LC-MS/MS), gut dysbiosis markers (3-indoxyl sulfate), and fatigue severity (FSS) against 40 age-matched healthy controls. Results: Baseline analysis revealed profound metabolic perturbations: elevated bacterial proteolytic markers (3-IS), substrate depletion (low tryptophan), and a neurotoxic signature (high quinolinic acid [QA], low kynurenic acid [KYNA]). Following the intervention, fatigue scores declined by 40.3%, with 97.5% of patients reaching the remission threshold (FSS < 36). Biochemically, 3-IS levels decreased to the range observed in healthy controls and attenuated xanthurenic acid levels. Although absolute QA concentrations remained elevated compared to controls, the neuroprotective KYNA/QA ratio increased significantly (+45%). Increased systemic tryptophan availability correlated directly with clinical symptom reduction (Spearman’s rho = −0.36, p = 0.024). Conclusions: The CDS22 formulation was associated with a restoration of intestinal eubiosis and functional tryptophan partitioning. Clinical remission coincides with a metabolic shift favoring neuroprotection (increased KYNA/QA ratio), validating the gut–kynurenine axis as a modifiable therapeutic target. Peripheral metabolic improvement relative to the healthy baseline appeared sufficient for symptom relief in this specific phenotype, despite incomplete clearance of neurotoxic metabolites. Full article

Oxidative stress (OS) reflects a pathologic imbalance between excessive production of reactive oxygen species (ROS) and insufficient antioxidant defenses. Growing evidence indicates that a healthy gut microbiota (GM) is essential for regulating redox homeostasis, whereas gut dysbiosis contributes to elevated ROS levels and oxidative damage in DNA, lipids, and proteins. This redox disequilibrium initiates a cascade of cellular disturbances—including synaptic dysfunction, altered receptor activity, excitotoxicity, mitochondrial disruption, and chronic neuroinflammation—that can, in turn, impair cognitive and social functioning in metabolic and neuropsychiatric disorders via epigenetic mechanisms. In this review, we synthesize current knowledge on (1) how OS contributes to cognitive and social deficits through epigenetic dysregulation; (2) the role of disrupted one-carbon metabolism in epigenetically mediated neurological dysfunction; and (3) mechanistic links between leaky gut, OS, altered GM composition, and GM-derived epigenetic metabolites. We also highlight emerging microbiota-based therapeutic strategies capable of mitigating epigenetic abnormalities and improving cognitive and social outcomes. Understanding the OS–microbiota–epigenetic interplay may uncover new targetable pathways for therapies aimed at restoring brain and behavioral health. Full article

Bacterial chondronecrosis with osteomyelitis (BCO), and its associated lameness, is one of the most common and devastating issues the poultry industry constantly faces, both globally and domestically. Leveraging the currently accepted “leaky gut” model of pathogenesis, this study aims to evaluate the cecal community of broilers reared under the aerosol transmission BCO induction model. A trial involving 1320 Cobb 500 broilers was conducted using the same induction model for 56 d with the following treatments: (1) positive control (PC)—untreated birds on wire-flooring pens; (2) negative control (NC)—untreated birds on litter-flooring pens; (3) LOW—birds treated with probiotic Enterococcus faecium spray on day-of-hatch (2.0 × 10⁹ CFU/bird); and (4) HIGH—birds treated with LOW spray combined with probiotic Bacillus amyloliquefaciens/Bacillus subtilis inclusion in the diet (492.1 mg/kg). Cecal contents were collected from six birds per treatment on d14, d28, d42, and d56 of the experiment; then, DNA was extracted and sent for 16 s V3–V4 amplicon sequencing. Returned sequences were assembled and taxonomically assigned, after which diversity indices were analyzed (including alpha, beta, and abundance). No significant effect was found between all treatments and positive/negative control groups in all timepoints, but timepoints were significantly different from each other in both alpha and beta diversity indices (p < 0.05). Abundance analysis also showed a high Bacillota:Bacteroidota ratio (average 18.87; p < 0.0001) with Bacillota (Firmicutes) dominating at 95.57% on average across all treatments, followed by Bacteroidota at 5.06% and Pseudomonadota at 2.59%. These findings characterize in detail the cecal microbiome in populations of broilers reared under the novel aerosol transmission induction model, offering further insights and possibilities into studies of BCO etiology and pathology. Full article

Autism spectrum disorder (ASD) is a neurodevelopmental condition mainly characterized by social impairments and repetitive behaviors. An altered intestinal barrier morphology and increased transmucosal leaks have also been implicated in ASD; in fact, comorbidities such as gastrointestinal problems (leaky gut) have frequently been reported in these patients. The regulation of tight junctions (TJs) is essential in maintaining intestinal barrier morphology and in regulating the delicate balance of trafficking between the intestinal lumen and the submucosa. To date, there are no definitive treatments for ASD comorbidities; however, melatonin (MLT) represents a well-validated and tolerated treatment for sleep disorders in ASD patients. The potential beneficial effects of MLT on this disorder have been and continue to be better investigated. In this context, the present study examines the effects of oral MLT administration (10 mg/kg/day for 16 weeks) on the intestinal barrier in BTBR T + Itpr3tf/J (BTBR) mice, a validated ASD model. Morphological analyses of the ileum of these animals reveal modified villus height (Vh), crypt depth (Cd), and Vh–Cd ratios; an inflammatory state; and a decrease in Paneth cells. Moreover, these mice showed altered TJ expression compared to the control animals (C57BL6/J mice). Notably, MLT normalizes morphological indices and TJ expression, consistent with an improved gut barrier morphology. These data collectively suggest that orally administered MLT can promote the remodeling of the intestinal barrier; thus, we can suppose that MLT reduces gastrointestinal barrier leaks. The overall safety and economy of MLT use suggest that this indolamine could be efficacious as an adjuvant therapy to reduce the condition known as leaky gut. Full article

Diet influences brain health through many connected metabolic and molecular pathways, and these effects are stronger in obesity. This review links diet quality with cognitive decline and dementia risk. Ultra-processed, high-fat, high-sugar diets drive weight gain, insulin resistance, and chronic inflammation. These changes trigger brain oxidative stress, reduce DNA repair, deplete NAD⁺, disturb sirtuin/PARP balance, and alter epigenetic marks. Gut dysbiosis and leaky gut add inflammatory signals, weaken the blood–brain barrier, and disrupt microglia. Mediterranean and MIND diets, rich in plants, fiber, polyphenols, and omega-3 fats, slow cognitive decline and lower dementia risk. Trials show extra benefit when diet improves alongside exercise and vascular risk control. Specific nutrients can help in certain settings. DHA and EPA support brain health in people with low omega-3 status or early disease. B-vitamins slow brain shrinkage in mild cognitive impairment when homocysteine is high. Vitamin D correction is beneficial when levels are low. A practical plan emphasizes healthy eating and good metabolic control. It includes screening for deficiencies and supporting the microbiome with fiber and fermented foods. Mechanism-based add-ons, such as NAD⁺ boosters, deserve testing in lifestyle-focused trials. Together, these measures may reduce diet-related brain risk across the life span. At the same time, artificial intelligence can integrate diet exposures, adiposity, metabolic markers, multi-omics, neuroimaging, and digital phenotyping. This can identify high-risk phenotypes, refine causal links along the diet–obesity–brain axis, and personalize nutrition-plus-lifestyle interventions. It can also highlight safety, equity, and privacy considerations. Translationally, a pattern-first strategy can support early screening and personalized risk reduction by integrating diet quality, adiposity, vascular risk, micronutrient status, and microbiome-responsive behaviors. AI can aid measurement and risk stratification when developed with privacy, equity, and interpretability safeguards, but clinical decisions should remain mechanism-aligned and trial-anchored. Full article

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disorder characterized by complex interactions between the innate and adaptive immune systems, being potentially associated with an enhanced intestinal permeability. Zonulin represents a key protein in the modulation of intestinal permeability, being a gut leakage marker. The purpose of the present work was to evaluate the intestinal permeability, through serum zonulin levels, and to explore the relationships between zonulin, disease activity, and organ involvement in Caucasian SLE patients. The study had a cross-sectional design and included two groups of subjects: the SLE group (n = 41) and the control group (n = 29). Plasma zonulin level was measured using indirect ELISA. Despite the fact that Caucasian SLE patients exhibited higher plasma zonulin levels compared to the control group (7.566 ± 1.368 ng/mL vs. 2.306 ± 0.286 ng/mL, p < 0.01, Mann–Whitney-U-test), plasma zonulin levels did not correlate with disease activity measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). SLE patients with clinical articular involvement had paradoxically lower plasma zonulin levels than those without this manifestation. The results support the hypothesis of a mutually exclusive inflammatory “signature” between intestinal mucosa and synovium. Full article

Phytotherapy is a growing field of modern medicine, offering natural alternatives with multidirectional pharmacological effects. Among plant-derived bioactive compounds, isoquinoline alkaloids exhibit antioxidant, anti-inflammatory, and antimicrobial properties. Our in vitro model of campylobacteriosis confirmed that berberine reduces pathological changes in colonocytes not only through its direct antibacterial (minimum inhibitory concentration for pure berberine against Campylobacter jejuni was 64 μg/mL) and anti-biofilm (fourfold reduction in C. jejuni biomass) effects, but also through its protective effect on the morphostructure and secretory profile of host cells exposed to bacterial components. Furthermore, berberine stabilized intercellular junction proteins, modulated bile acid and arachidonic acid metabolism, and supported host-protective signaling pathways. These findings indicate that berberine acts through a dual mechanism—directly reducing bacterial virulence while enhancing intestinal barrier integrity and metabolic homeostasis. In summary, berberine appears to be a multifunctional phytochemical in the development of new strategies for the prevention and treatment of C. jejuni-induced gastrointestinal infections and epithelial barrier dysfunctions. The protective effect we have demonstrated may contribute to alleviating the phenomenon of “leaky gut,” commonly associated with campylobacteriosis. Full article

Background/Objective: Larazotide acetate (LA) is a synthetic octapeptide under development as a therapeutic candidate for celiac disease, acting to reduce intestinal permeability and regulate tight junctions (TJs). Although several studies have shown barrier-protective effects, the cellular mechanisms underlying LA’s actions in the intestinal epithelium remain unclear. This study aimed to elucidate the mechanistic roles of LA in maintaining intestinal epithelial integrity during cellular injury. Methods: C2BBe1 and leaky IPEC-J2 cell monolayers were pretreated with 10 mM LA and subjected to anoxia/reoxygenation (A/R) injury. Transepithelial electrical resistance (TEER), TJ protein localization, and phosphorylation of myosin light chain-2 (MLC-2) were analyzed. In addition, RNA sequencing was conducted to identify differentially expressed genes and signaling pathways affected by LA treatment. Results: LA pretreatment significantly increased TEER and preserved TJ protein organization during A/R injury. Transcriptomic analysis revealed enrichment of genes related to barrier regulation, small GTPase signaling, protein phosphorylation, proliferation, and migration. LA pretreatment markedly reduced MLC-2 phosphorylation, likely through modulation of the ROCK pathway, consistent with RNA-seq findings. Moreover, LA enhanced cellular proliferation, validating transcriptomic predictions. Conclusions: LA exerts a protective effect on intestinal epithelial integrity by stabilizing tight junctions, reducing MLC-2 phosphorylation, and promoting epithelial proliferation. These findings highlight a novel mechanism for LA and support its therapeutic potential in treating gastrointestinal disorders associated with “leaky gut” and mucosal injury. Full article

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

Gut microbial modulation through diet is central to human health and disease. Despite tremendous effort in understanding the impact of nutrients and drugs on the gut microbiota, and attempts to develop dietary strategies that facilitate gut-beneficial effects, several erroneous gut microbiota-associated concepts remain prevalent in popular belief. This article discusses widespread misconceptions about the gut microbiota, contrasting them with contemporary scientific facts. In this article, ten prevalent myths, including the obsolete 10:1 bacteria-to-human-cell ratio, the reductive categorization of microbes as ‘good’ or ‘bad’, and the discredited universal biomarker status of the Firmicutes/Bacteroidetes ratio in relation to metabolic diseases, have been debunked. Essential facts highlighting the context-dependency of the microbiome, considerable inter-individual heterogeneity, and dynamic reactivity to dietary changes are discussed. This questions the assumptions that increased diversity always signifies health, that probiotics are intrinsically safe, that fecal microbiota transplantation is a universal remedy, or that leaky gut syndrome constitutes a clearly defined diagnosis. It is highlighted that eubiosis and dysbiosis do not possess uniform criteria, and microbiome–drug interactions are extremely individualized. The gut microbiota operates as a dynamic, adaptive ecosystem, necessitating sophisticated, evidence-based methodologies for study and therapeutic application, transcending simplistic misconceptions in favor of tailored insights and therapies. Full article

The global increase in life expectancy underscores the need to promote healthy aging, particularly by addressing age-related leaky gut syndrome, which contributes to systemic inflammation and chronic disease. This study focused on the sustainable production and functional development of Ulva meridionalis, a fast-growing seaweed, to improve gut health and mitigate the effects of aging. Using land-based aquaculture, a scalable cultivation system for U. meridionalis was established, and its polysaccharide, ulvan, was extracted. Ion exchange treatment enhanced the functionality of ulvan to produce ulvan-Na, which contains high levels of Na⁺ and conveys superior anti-aging properties. Ulvan-Na restored intestinal barrier integrity in aged mice by reducing serum LPS levels and increasing claudin-1 expression. Ulvan-Na modulated the gut microbiota, increasing beneficial bacteria such as Clostridiales vadin BB60 and suppressing inflammatory bacteria such as Turicibacter. The mechanism was clarified whereby ulvan-Na activates β-catenin to enhance claudin-1 expression. These findings highlight ulvan-Na as a bioactive compound that ameliorates age-related intestinal dysfunction while demonstrating the feasibility of sustainable U. meridionalis production for functional food innovation and environmental conservation. 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

This study focuses on the issue of whether orally administered zinc (gluconate) (26 mg BID) can induce the remodeling of gastrointestinal barrier function and reduce passive leak across the human intestinal mucosal barrier in situ. Increased transmucosal leak has been implicated in diseases as diverse and seemingly unconnected as Inflammatory Bowel Disease (IBD), Celiac Disease, Autism Spectrum Disorders and Alzheimer’s Dementia. Our current investigation represents the first patient-based study to examine the effect of zinc on gastrointestinal epithelial tight junctions and gastrointestinal barrier leak in otherwise healthy test subjects. Using independent test subject groups for each endpoint, three separate molecular analyses indicated that zinc treatment can achieve a positive outcome: (1) RNA-seq analyses of intestinal biopsies showed salutary patterns of gene transcription changes dealing with not only transcripts of junctional proteins but also transcripts mitigating the proinflammatory state, as well as dedifferentiation (both modulators of tight junction permeability); (2) Western immunoblot analyses of intestinal tissue indicated that tight junctional protein expression was being modified by the administered zinc, most notably Claudin-2 and Tricellulin; (3) zinc treatment induced a reduction in serum levels of a functional marker of passive intestinal leak, namely the GI microbiome metabolite D-Lactate. The data collectively suggest that orally administered zinc can induce remodeling of the intestinal epithelial barrier, resulting in the reduction in GI barrier leak. The overall safety and economy of supplement levels of zinc suggest that this micronutrient could be efficacious as an adjuvant therapy to reduce the condition known as leaky gut, and possibly therefore be protective regarding diseases postulated to involve leaky gut. Full article

Background/Objectives: Gut microbial dysbiosis, leaky gut, and increased transepithelial translocation of commensal bacteria have been documented in multiple sclerosis (MS). Intrathecal IgGs specific for Akkermansia muciniphila, a gut bacterium, are increased in patients with MS and associated with clinical disability. Our objective here was to explore the putative involvement of intrathecal anti-A. muciniphila IgG in MS pathogenesis by characterizing patients with different anti-A. muciniphila IgG indices. Methods: Serum and intrathecal IgG specific for A. muciniphila and other gut bacteria, as well as routine cerebrospinal fluid (CSF) parameters, were measured in 61 patients with MS. Examination of these patients included immunophenotyping of CSF-infiltrating and paired circulating lymphocytes, intrathecal markers of neurodegeneration and inflammation, and a detailed characterization of demographic, clinical, and magnetic resonance imaging (MRI) features. Results: Plasma blasts (p < 0.01), B cells (p < 0.01), and Th2 cells (p < 0.01), which might be involved in antibody production, were increased in the CSF of these patients, as well as blood pro-inflammatory Th17 cells (p < 0.05). Anti-A. muciniphila IgG indices were negatively associated with blood-brain barrier (BBB) permeability and circulating monocytes (p < 0.001), and positively with brain lesion load (p < 0.01). Conclusions: The differences between patients with low and high anti-A. muciniphila IgG indexes regarding BBB permeability, CSF cell infiltrates, and pro-inflammatory peripheral immune cells, as well as imaging features, support a role of anti-A. muciniphila immune response in MS pathogenesis. Full article

The human gut microbiota, which can weigh as much as 2 kg and harbor 100 trillion bacteria, is specific to each individual. In healthy adults, a balanced microbiota—a state known as eubiosis—can be altered by various factors such as diet and lifestyle. Microbiota imbalance—or dysbiosis—can have consequences for host health. Given that 80% of the human immune system is located in the gut, studies have investigated the role of the microbiota in immune system diseases, including joint and inflammatory pathologies such as rheumatoid arthritis. A better understanding of this pathology might enable the development of new treatments in the future. The microbiota includes all unicellular organisms in the digestive tract, including bacteria, viruses, fungi, and archaea. This complex ecosystem is unique to each individual. Associations between the human body and the microorganisms that it hosts can be considered mutualistic, symbiotic, or parasitic. These microorganisms are responsible for essential functions in maintaining health; the microbiota can even be considered another organ of the body. Microbiota composition varies considerably between early life and older age but remains relatively stable for most of a lifespan. Full article