Search Results (736)

Gastrointestinal (GI) cancers account for a quarter of all cancer cases worldwide and are responsible for a third of cancer deaths. One of the characteristic features of GI tissue is its multilayered structure, which, in addition to multiple scattering, complicates optical spectral analysis. The use of spectroscopic diagnostics and photodynamic therapy for the detection and treatment of GI cancer is a rapidly developing field. The method proposed in this paper for layer-by-layer optical properties assessment, suitable for real-time clinical application to the walls of hollow organs, allows us to calculate the absorbed dose layer by layer. This paper proposes a method for recording spectral data in two geometries, diffuse reflectance and transmission, using light delivery from both the external and internal surfaces of the gastrointestinal tract wall. Layer-by-layer assessment of optical properties was performed using a developed algorithm based on the inverse adding–doubling method with initial optical properties values determined using the modified two-stream Kubelka–Munk model with the accuracy equal to 86 ± 13%. The method was approved in clinical conditions. Based on the results of the work, the developed method for assessing the optical properties of multilayered biological tissues exhibited sufficient speed and accuracy for in vivo application to personalize laser-induced therapy by correction of the laser dose. Full article

The gut–microbiota–brain axis (GMBA), an intricate network connecting the gastrointestinal (GI) tract and the brain, plays a pivotal role in maintaining overall health and influencing disease processes. The human gut microbiota, comprising over 3000 bacterial species, regulates immune responses, hormonal signals, and metabolite production, maintaining homeostasis under normal conditions. Dysbiosis, or microbial imbalance, has been linked to various central nervous system (CNS) disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and autism spectrum disorder (ASD). Given the growing interest in this topic and the limited effectiveness of current therapeutic strategies for managing patients with AD, the purpose of the current narrative review is to analyze the pathophysiological role of the GMBA in the pathogenesis of AD and assess potential therapeutic strategies targeting the GMBA, particularly the microbiome and its metabolites. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science to identify clinical studies, experimental research, and review articles examining the GMBA in health and AD, as well as related therapeutic strategies. The search terms included “Alzheimer’s disease”, “neuroinflammation”, “amyloid-beta”, “tau”, “gut–brain axis”, “microbiome”, “short-chain fatty acids”, “probiotics”, “prebiotics”, and “fecal microbiota transplantation”. In AD, altered gut microbiota composition is associated with neuroinflammation, neurodegeneration, and exacerbation of disease progression. Probiotics have shown potential in enhancing cognitive function and reducing neuroinflammation by modulating microbiota composition and influencing brain-derived neurotrophic factor (BDNF) levels. Prebiotics, through their impact on gut microbiota and metabolite production, also offer therapeutic promise by improving cognitive function and mitigating neuroinflammation. With its historical and modern applications, fecal microbiota transplantation (FMT) may represent a potential strategy for addressing dysbiosis and its neurological implications. This manuscript focuses on GMBA and its effects on neuroinflammation, neurodegeneration, and CNS health while emphasizing the need for further research into microbiome-based therapies and the gut–brain relationship in patients with AD. Full article

Prolonged endurance exercise performed in hot ambient conditions is associated with an increased prevalence of performance-limiting gastrointestinal perturbations. This study aimed to examine the associations between biomarkers of exercise-induced gastrointestinal syndrome (EIGS) and exercise-associated gastrointestinal symptoms (Ex-GIS) under exertional heat stress (EHS). Fifty-six non-heat acclimated endurance-trained individuals completed 2 h of steady state running at 60% maximal oxygen uptake ($\stackrel{.}{V}{\mathrm{O}}_{2\max }$) with an ambient temperature of 35.1 °C and relative humidity 29.4%. Venous blood samples were collected immediately pre- and post-exercise to quantify plasma concentrations of gastrointestinal epithelial injury and systemic inflammatory biomarkers, whilst gastrointestinal symptoms were recorded at regular intervals throughout the exercise protocol. Spearman’s rank correlation identified moderately significant relationships between interleukin-6 (IL-6) with defecation-bloody stools; interleukin-10 (IL-10) with upper abdominal pain; and IL-10, IL-1 receptor antagonist (IL-1ra), and systemic inflammatory response (SIR) profile with flatulence. Simple linear regression demonstrated that IL-6 explained a small but significant proportion of the variance defecation-bloody stool (adjusted R² = 0.094, p = 0.024); whilst variance in flatulence was independently explained by IL-10 (adjusted R² = 0.138, p = 0.025), IL-1ra (adjusted R² = 0.122, p = 0.033), and SIR-Profile (adjusted R² = 0.112, p = 0.040). These findings suggest that Ex-GIS development is multifactorial in aetiology and pathophysiology, and that symptom reporting alone likely underestimates perturbations to the gastrointestinal tract during EHS. Full article

Background: The upper gastrointestinal (GI) tract is a complex environment characterized by sharp physicochemical gradients. While the oral microbiome is a major source of microbial seeding for downstream organs, it remains unclear how these communities correlate and diverge across different anatomical sites. This study provides a high-resolution re-analysis of a comprehensive multi-site dataset to delineate the microbial architecture and ecological signatures along the oral–upper GI axis. Method: Human oral, esophageal, gastric mucosal, and gastric juice microbiome sequencing data were retrieved from the publicly available National Center for Biotechnology Information (NCBI) BioProject PRJNA1049979 database. Using these publicly available 16S rRNA sequencing data, we performed an integrated ecological analysis. Microbial diversity, taxonomic composition, and niche-specific community structures were evaluated using Quantitative Insights Into Microbial Ecology 2 (QIIME2) and R-based tools, including linear discriminant analysis effect size (LEfSe) and phylogenetic mapping. Results: The esophageal microbiome showed significantly greater richness and evenness than the oral cavity and stomach. Beta diversity analysis demonstrated clear compositional separation between oral and downstream upper GI communities, whereas gastric samples, particularly gastric juice, showed greater heterogeneity. Although major phyla were shared across sites, their relative abundances differed markedly. Oral samples were enriched with periodontal-associated taxa, including Porphyromonas, Prevotella, Alloprevotella, and Fusobacterium. In contrast, gastric mucosal samples were enriched with Akkermansia muciniphila and Helicobacter pylori, whereas gastric juice was characterized by Sarcina ventriculi, Fusobacterium periodonticum, and Clostridium perfringens. These findings indicate both taxonomic continuity and pronounced site-specific ecological divergence along the oral–upper GI axis. Conclusion: The oral cavity, esophagus, stomach, and gastric juice share a common microbial framework but exhibit distinct community restructuring driven by local environmental selection. This study provides a detailed ecological view of the oral–upper GI microbiome and highlights the importance of site-specific microbial organization in upper GI health and disease. Full article

Eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) are immune-mediated disorders of the gastrointestinal (GI) tract that, despite involving different tissues, are increasingly recognized to coexist. Epidemiologic studies demonstrate a bidirectional association, with patients affected by one condition showing a higher-than-expected prevalence of the other, suggesting shared susceptibility rather than incidental overlap. Genetic and epigenetic data support partial convergence in immune regulatory pathways, while epithelial barrier dysfunction and antigen-driven immune activation emerge as common upstream features. Overlapping cytokine networks, including IL-4, IL-13, and IL-23 signaling, contribute to chronic inflammation in both diseases, although differences in tissue environment and immune dominance give rise to distinct inflammatory phenotypes and clinical behavior. Clinical outcomes in patients with dual diagnoses appear heterogeneous, with available data suggesting neither uniformly worsened nor clearly protective disease courses, underscoring the complexity of shared immune mechanisms operating within different anatomic contexts. Beyond inflammatory activity, coexistence of EoE and IBD poses important nutritional and quality-of-life challenges, as overlapping dietary restrictions and chronic symptoms increase the risk of malnutrition, micronutrient deficiencies, and psychosocial burden. Current therapies remain disease-specific, with strong evidence supporting proton pump inhibitors, swallowed topical steroids, dietary therapy, and dupilumab in EoE, and biologics and small molecules targeting TNF-α, IL-12/23, IL-23, integrins, and JAK–STAT signaling in IBD, while evidence guiding treatment in patients with dual diagnosis remains limited. Together, current evidence supports a framework of shared immune machinery with tissue-specific expression that explains coexistence while preserving the distinct identities of EoE and IBD. By integrating emerging genetic, immunologic, and clinical evidence, this review aims to provide a framework for understanding and managing patients with coexisting EoE and IBD. Full article

Oral administration remains the most convenient and favored route for systemic delivery of small-molecule drugs, primarily due to patient compliance and the absence of invasive procedures. Yet, poor aqueous solubility, chemical/enzymatic instability, and limited permeability in the gastrointestinal (GI) tract often result in low bioavailability (BA) of many therapeutic agents. Polymeric micelles formed from the self-assembly of amphiphilic block copolymers have gained considerable attention as a nanotechnology-driven solution to overcome these challenges. Their hydrophobic core–hydrophilic shell structure enables efficient encapsulation of poorly soluble small molecule drugs, providing protection from acidic or enzymatic degradation while potentially enhancing drug transport across the intestinal epithelium. This review examines the design principles, formulation strategies, and in vivo performance of polymeric micelles for oral delivery of small molecule drugs. We discuss strategies to improve micelle stability in the GI environment, including optimization of core hydrophobicity, kinetic stabilization, and corona engineering, and compare polymeric micelles with established alternatives such as self-micro emulsifying drug delivery system (SMEDDS) and amorphous solid dispersions (ASDs) across critical performance parameters. Despite decades of preclinical progress, no oral polymeric micelle formulation has reached regulatory approval, underscoring the persistent challenge of maintaining micellar structural integrity under the dynamic conditions of the GI environment. This review therefore examines not only the promise but also the structural vulnerabilities of oral micelles, proposing a stability-centered framework for interpreting micelle function under GI conditions. Finally, we discuss current translational challenges and suggest directions for future research toward clinical application of oral polymeric micelle systems. Full article

Micro- and nanoplastics (MNPs) are pervasive in food-contact environments and the human diet, positioning the gastrointestinal (GI) tract as the primary portal of entry and a plausible site of early biological effects. Human exposure is supported by detection of microplastics in stool and colon tissue, and emerging clinical studies report associations between fecal microplastic burden and GI disease states, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). Preclinical studies provide mechanistic plausibility, reporting that ingested MNPs can modulate microbial ecology, alter mucus membrane integrity, increase intestinal permeability through changes in cellular tight junction biology, and induce inflammatory gene expression. These effects can vary by MNP polymer type, particle size/shape, aging state, and exposure dose. Human-relevant experimental platforms increasingly demonstrate size- and concentration-dependent uptake and host responses while revealing substantial inter-individual variability. We synthesize current evidence on dietary sources and key physiochemical properties as they relate to mechanistic pathways connecting MNP exposure to dysbiosis–immune activation–neoplasia axes, in addition to methodological limitations that constrain current clinical utility. Further research including standardized biomonitoring and exposure protocols, environmentally realistic chronic low-dose mixtures, longitudinal human cohorts, and interventional designs that test whether exposure reduction modifies GI inflammation biomarkers and cancer-relevant pathways are critical to clarifying causality. Full article

Background: Homologous recombination deficiency (HRD) is emerging as a clinically relevant biomarker across diverse tumor types, in addition to ovarian cancer. In this study, we evaluated the genomic instability score (GIS) across multiple tumor types using the TruSight Oncology 500 HRD assay, which incorporates the Myriad Genetics GIS algorithm, a widely used reference standard for HRD assessment. Methods: A total of 162 tumor samples (17 ovarian cancers and 145 non-ovarian tumors) underwent next-generation sequencing using the TruSight Oncology 500 HRD assay. Results: A total of 14 tumors were classified as GIS-High, defined as a GIS score ≥42, representing 8.6% of all cases. Among ovarian cancers, 7 out of 17 cases (41.2%) met the GIS-High threshold. Among non-ovarian tumors, seven GIS-High tumors were identified, accounting for 4.8% of cases (7/145). GIS-High cases occurred in breast (n = 4), lung (n = 2), and hepatobiliary tract (n = 1) cancers. GIS scores showed significant associations with BRCA1/2 and TP53 mutational status. In contrast, alterations in HRD-related genes other than BRCA1/2 did not show significant associations with GIS score. Conclusions: GIS-High tumors were identified in a small subset of non-ovarian cancers. These findings support further investigation of GIS as an exploratory biomarker of HRD-like genomic scarring beyond ovarian cancer, but its predictive and therapeutic relevance in non-ovarian tumors requires additional validation. Full article

Probiotics can promote gut health, but their efficacy is often limited by low viability and metabolic activity in the gastrointestinal (GI) tract. This study aimed to develop protective hydrogels for encapsulating Lactiplantibacillus plantarum CJLP 133 using a composite matrix of sodium alginate (SA) and cellulose nanofibers (CNFs). L. plantarum CJLP 133-loaded hydrogel beads were fabricated via the ionic gelation technique using an optimized formulation of SA and CNF. Scanning electron microscopy revealed that CNF integration improved spherical morphology with reduced surface cracking. Fourier transform infrared spectroscopy confirmed the formation of intermolecular hydrogen bonds between SA and CNF. CNF integration also reduced gumminess and chewiness, resulting in a softer texture. The survival rate of L. plantarum CJLP 133 remained high following thermal exposure and freeze-drying. The in vitro GI delivery system demonstrated a protective swelling profile in stimulated gastric fluid and a targeted, highly efficient release profile in stimulated intestinal fluid. Finally, the 3% SA + 0.5% CNF hydrogel with L. plantarum CJLP 133 exhibited significant synbiotic effects, enhancing probiotic growth, intestinal adhesion, and butyrate and succinate production. These results suggest that the SA/CNF-based hydrogel is an effective delivery system that ensures the targeted release of probiotics within the GI tract. Full article

The hypothalamic–pituitary–somatotropic (HPS) axis, which includes growth hormone (GH) and insulin-like growth factor 1 (IGF-1), is one of three endocrine systems that show a decline in hormone concentration with age. Among the hypothalamic hormones involved in the aging process, GH-releasing hormone (GHRH) and somatostatin (SST) are most affected, resulting in several age-related changes. The pathophysiology of GH decline in the aging process is unclear, specifically, whether it results from decreased GHRH or increased SST levels. Similarly, it is not known whether quantitative changes in hypothalamic peptides (including SST) precede or follow age-related pathological behavioral changes. SST is produced mainly by cells of the central nervous system (CNS) and the gastrointestinal (GI) tract, which are functionally interconnected systems that undergo significant changes during aging. The physical changes in the aging organism are considered physiological, and experimental evidence indicates that a large proportion of these changes are the result of declining hormonal activity (including the SST system). It is particularly important to understand the role of SST in diseases of old age, which affect both cognitive processes and memory (e.g., Alzheimer’s and Parkinson’s diseases) and the proper functioning of the GI tract and pancreas (e.g., obesity, type 2 diabetes mellitus, and colorectal cancer). This narrative review discusses systemic and peripheral changes in SST production and secretion observed in aging individuals and their potential association with selected diseases of old age, especially CNS and GI tract diseases. Understanding the role of SST expression with age will enable the better application of this neuropeptide in the diagnosis and treatment of diseases of old age (including cancers). Full article

Phage therapy has enormous potential in combating bacterial resistance in food animals. However, its application via the oral route remains limited due to challenges associated with the gastrointestinal tract (GIT) environment and a lack of rigorous clinical trial evidence. Therefore, we systematically searched in Google Scholar, PubMed, Scopus, and Web of Science databases following PRISMA guidelines and finally identified 111 articles on oral phage therapy in food animals from where we summarized the key physiological and chemical factors of the gut environment hindering the effectiveness of oral phage therapy (OPT), examined the methods used to evaluate phage stability in the GI environment, and highlighted potential strategies to mitigate these challenges. In addition, we performed quantitative analysis to visualize in vitro pH and thermal stability patterns of phages targeting bacteria isolated from food animals and variability in buffer and incubation period across stability studies. The GIT consists of several anatomically and functionally distinct segments, where complex interactions occur among digestive enzymes, gastric acids, electrolytes, commensal microbiota, and mucosal immune components. The acidic pH of the stomach is a major barrier to successful oral phage delivery. According to our analysis of pH stability testing data from the reviewed studies, most phages targeting antimicrobial-resistant bacteria in food animals remained stable at pH 5–9 and inactivated under highly acidic (pH ≤ 2) or highly alkaline (pH ≥ 11) conditions. In addition, phages are susceptible to high temperatures (above 60 °C), digestive enzymes (e.g., pepsin, trypsin, lipases), bile salts, and host immune responses. Several in vitro laboratory techniques are available to assess phage stability under simulated GI conditions, but variations occur in the assessment protocols. Microencapsulation using alginate and chitosan has been used to protect phages from the adverse GI environment. Additionally, enteric-coated capsules, antacids, co-encapsulation with acid-neutralizing agents, consumption of alkaline water, and daily phage administration are suggested to improve phage survival and efficacy. For the successful clinical implementation of OPT in food animals, future research should focus on elucidating the molecular and physicochemical determinants of phage stability, understanding the humoral immune response to OPT, standardizing laboratory protocol for assessing phage viability, improving the scalability of encapsulation methods, and exploring other potential delivery techniques. Full article

Eosinophils are multifunctional granulocytes that reside constitutively within mucosal tissues, where they engage in bidirectional communication with the epithelial cells lining the respiratory and gastrointestinal (GI) tracts. Once regarded solely as terminal effectors of the type 2 immunity, eosinophils are now recognized as key regulators of epithelial homeostasis and barrier integrity. Epithelial cells initiate crosstalk by releasing the alarm cytokines such as interleukin (IL)-33, thymic stromal lymphopoietin (TSLP), and IL-25, which drive eosinophil recruitment, activation, and tissue retention. Conversely, eosinophils modulate epithelial function through the release of granule proteins, cytokines, and growth factors with both damaging and reparative consequences. In the airway, this crosstalk underpins the pathogenesis of eosinophilic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), in part via eosinophil-derived mediators that disrupt tight junction integrity and fuel remodeling. In the GI tract, homeostatic eosinophils support villous architecture, epithelial turnover, and goblet cell differentiation through microbiota-driven IL-33 signals and neuropeptide-mediated neuroimmune pathways, whereas dysregulated crosstalk promotes eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD). This review synthesizes recent research to delineate the molecular mechanisms of eosinophil–epithelial crosstalk across mucosal compartments, highlight tissue-specific differences and shared mechanistic themes, and discuss the implications of these findings for targeted therapy. Full article

Chemotherapy-induced mucositis (CIM) is a dose-limiting toxicity of cancer therapy that is mainly associated with mitochondrial dysfunction in epithelial cells. We investigated whether GV1001, a mitochondrial protective peptide from human telomerase reverse transcriptase (hTERT), attenuates 5-fluorouracil (5-FU)-induced mucositis in a murine model. 5-FU induced notable mortality, leukopenia, and mucositis in the gastrointestinal (GI) tract, including tongue, esophagus and small intestine. It promoted epithelial–mesenchymal transition (EMT), nuclear factor kappa-B (NF-κB) activation, systemic and mucosal inflammation, DNA damage, impaired cell proliferation, and apoptosis throughout the GI tract. GV1001 blocked 5-FU–associated mortality, significantly attenuated leukopenia, and notably prevented mucositis. GV1001 also suppressed 5-FU-induced DNA damage, EMT, loss of proliferative capacity, apoptosis, and NF-κB activation in mucosal epithelium. In normal human keratinocytes, 5-FU inhibited the cell proliferation, disrupted mitochondrial function, as evidenced by reduced mitochondrial membrane potential, increased reactive oxygen species (ROS) production, impaired electron transport chain (ETC) complex integrity, decreased ATP synthesis, and cytochrome c release into the cytosol. GV1001 markedly mitigated these 5-FU-induced mitochondrial defects. Taken together, GV1001 mitigates CIM by most likely preserving mitochondrial integrity and function, supporting its potential as a strategy to prevent cancer chemotherapy-associated mucosal injury in patients. Full article

Background: Rome IV criteria promote a symptom-based (“positive”) diagnosis of pediatric disorders of gut–brain interaction (DGBIs). In clinical practice, however, organic gastrointestinal diseases may mimic DGBIs and lead to diagnostic revision after further evaluation. We aimed to quantify the diagnostic stability of an initial Rome IV-oriented functional diagnosis in a tertiary pediatric outpatient setting and to identify symptom phenotypes associated with a higher likelihood of later organic reclassification. Methods: We performed a single-center retrospective cohort study (2014–14 May 2021) based on outpatient chart review. Eligible patients were children and adolescents aged 0–18 years with an initial Rome IV-oriented functional diagnosis. Diagnostic reassessment was based on follow-up data, available laboratory and instrumental investigations, and/or response to exclusion therapies. Final diagnoses after reassessment were categorized as functional only, organic, or mixed. Groups were compared using Pearson’s chi-square test. Results: The cohort included 220 males (50.0%) and 220 females (50.0%), with a mean age of 8.86 ± 4.65 years. After reassessment, 343/440 (77.95%) remained functional, 73/440 (16.59%) were reclassified as organic, and 24/440 (5.45%) were classified as mixed. Final diagnosis differed by GI tract involvement (p = 0.001) and by symptom cluster (p = 0.001). Upper GI/dyspepsia-spectrum presentations showed the highest organic yield (27.03%), followed by lower abdominal pain/IBS-spectrum presentations (19.61%). Diarrhea and vomiting/cyclic vomiting each showed 16.67% organic diagnoses (mixed: 10.0% and 7.14%, respectively), whereas constipation showed the greatest diagnostic stability (98.89% functional; 1.11% organic). Functional confirmation rates were similar before and during the pandemic (77.71% vs. 78.70%; p = 0.756). Monthly case volume was higher in 2020–2021 (6.29 vs. 4.61 cases/month). Conclusions: In this tertiary cohort, about one in six children initially diagnosed with a functional disorder were later found to have an organic disease, and an additional 5% had mixed organic–functional presentations. Diagnostic revision was associated with presenting phenotype, with the highest organic yield observed in dyspepsia/upper GI presentations and the lowest in constipation. These findings support symptom-stratified evaluation and follow-up alongside Rome IV criteria. Full article

Equitable access to rehabilitation services is essential for individuals living with a disability, yet geographic disparities in outpatient rehabilitation care remain understudied. This study examined spatial accessibility to outpatient physical and occupational therapy services across Texas to identify regional inequities and inform workforce and policy planning. A descriptive cross-sectional geospatial analysis was conducted using outpatient clinic location data from the Texas Health and Human Services database (2022) and population data from the 2020 U.S. Census. Clinic addresses were verified and geocoded. Accessibility was measured using an origin–destination cost matrix to estimate the travel time to the nearest clinic, and the two-step floating catchment area (2SFCA) method to calculate an accessibility index. Spatial clustering of access was assessed using the Getis-Ord Gi* statistic to identify hot and cold spots. The analysis included 2255 outpatient rehabilitation clinics across 6896 census tracts. Travel times varied substantially, with rural areas experiencing the longest travel burdens. The 2SFCA analysis revealed pronounced disparities, with low-accessibility clusters concentrated in rural and border regions and high-accessibility clusters in urban metropolitan areas. These findings demonstrate persistent geographic disparities in outpatient rehabilitation access across Texas, suggesting the need for targeted workforce placement, transportation investment, and policy interventions to improve equitable access. Full article