Search Results (780)

Background and aim: Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract resulting from a complex interplay among genetic susceptibility, immune dysregulation, environmental factors, and alterations in the gut microbiota. Among these, diet has emerged as a key modifiable factor influencing intestinal inflammation, barrier integrity, and disease progression. This review aims to critically evaluate the role of dietary patterns and food additives in the pathogenesis and management of Crohn’s disease, with particular emphasis on their effects on intestinal inflammation, epithelial barrier function, and host–microbiota interactions. Methods: A comprehensive literature search was conducted using the PubMed, Scopus, and Web of Science databases up to March 2026. Clinical trials, observational studies, and mechanistic research were included based on their relevance to dietary factors, food additives, and intestinal inflammation in CD. Evidence was synthesized narratively to integrate clinical and experimental findings. Results: Dietary interventions such as the Crohn’s disease exclusion diet (CDED), specific carbohydrate diet (SCD), low-FODMAP diet, and Mediterranean diet (MD) demonstrate varying degrees of efficacy in improving clinical symptoms and, in some cases, inflammatory markers. In contrast, high consumption of ultra-processed foods is consistently associated with increased disease risk and activity. Emerging evidence highlights the role of food additives—particularly emulsifiers and artificial sweeteners—in disrupting gut barrier integrity, promoting dysbiosis, and enhancing inflammatory responses. Recent human studies further suggest that exposure to these compounds may correlate with disease activity, supporting their potential role in CD pathophysiology. Conclusions: Diet plays a significant adjunctive role in the management of Crohn’s disease. Reducing exposure to ultra-processed foods and potentially harmful food additives, while promoting balanced dietary patterns, may improve clinical outcomes. Further research is needed to clarify long-term effects and to develop personalized, evidence-based nutritional strategies for patients with CD. Full article

Background/Objectives: Intestinal diseases are a major global health problem due to their high prevalence, chronic course, and significant impact on quality of life. Increasing attention has been given to the extra-skeletal effects of vitamin D, particularly its role in immune regulation, maintenance of intestinal barrier integrity, and modulation of the gut microbiota. The aim of this review was to evaluate current evidence regarding the role of vitamin D in immune regulation, intestinal barrier function, and the pathogenic mechanisms of intestinal diseases, including inflammatory and functional gastrointestinal disorders. Methods: A structured narrative review was conducted using the PubMed, Scopus, and Web of Science databases to identify publications addressing the role of vitamin D in intestinal diseases. The literature search was updated in May 2026 and included studies published between 2004 and 2026. The aim of this review was to summarize current evidence on the effects of vitamin D on immune regulation, intestinal barrier integrity, gut microbiota, and their clinical relevance in intestinal diseases. Results: The included studies demonstrated that vitamin D plays an important role in maintaining intestinal homeostasis through regulation of innate and adaptive immune responses, preservation of epithelial barrier integrity, and modulation of gut microbiota composition. Vitamin D deficiency was associated with impaired VDR-dependent signalling, increased intestinal permeability, dysbiosis, and enhanced pro-inflammatory immune responses, which may contribute to the development and progression of inflammatory bowel disease, Crohn’s disease, ulcerative colitis, irritable bowel syndrome, and celiac disease. Conclusions: Current evidence supports the important role of vitamin D in immune regulation, intestinal barrier protection, and maintenance of gut microbial balance. Further clinical studies are required to better understand its therapeutic potential in intestinal diseases. Full article

Background/Objectives: Inflammatory bowel disease (IBD) is a chronic and recurrent gastrointestinal disorder characterized by intestinal inflammation and gut microbiota dysbiosis, but current therapies remain limited by adverse effects and suboptimal long-term efficacy. Methods: Here, using a dextran sulfate sodium (DSS)-induced mouse model of IBD-like colitis, we investigated the protective effects of Yakuchinone B (YB)—a diarylheptanoid derived from Alpinia oxyphylla with reported anti-inflammatory and antioxidant activities—against inflammatory bowel disease (IBD). Results: YB supplementation significantly alleviated colitis symptoms, as evidenced by reduced body weight loss, lower disease activity index scores, attenuated colonic shortening, and ameliorated histopathological damage. YB also decreased the colonic and serum levels of TNF-α, IL-1β, and IL-6. Microbiome profiling showed that YB restored gut microbial diversity and reshaped microbial composition, with increased abundances of Alistipes and Duncaniella and reduced overgrowth of Akkermansia. Untargeted metabolomics revealed that YB modulated colitis-associated pathways, including purine metabolism, alanine, aspartate, and glutamate metabolism, and steroid hormone biosynthesis. Targeted analysis further showed that YB increased acetate, propionate, and butyrate levels. Conclusions: These results collectively suggest that YB ameliorates DSS-induced colitis by attenuating inflammation, associated with modulation of the gut microbiota-host metabolism axis, and promoting short-chain fatty acid production, supporting its potential as a promising functional dietary candidate for IBD management. Full article

This review consolidates current knowledge on the phytochemical composition, traditional uses, pharmacological properties, and industrial application of Ricinus communis L. This plant belongs to the Euphorbiaceae family and is a globally distributed plant of considerable medicinal and industrial importance. It is rich in bioactive compounds, notably ricinoleic acid as the dominant fatty acid in seed oil, as well as ricin, ricinine, phenolic acids and flavonoids distributed across different plant parts. Variations in phytochemical profiles among cultivars and tissues are influenced by genetic and environmental influences. Traditional medicinal uses of the leaves, roots, seeds, and oil, particularly for inflammatory conditions, pain, infections, wound healing, and gastrointestinal disorders, are critically examined in relation to experimental pharmacological evidence. Castor oil extracted from the R. communis plant remains central to the plant’s industrial value, serving as a renewable feedstock for pharmaceuticals, cosmetics, polymers, lubricants, and biofuels due to the unique hydroxyl functionality of ricinoleic acid. However, the presence of the highly toxic protein ricin in unprocessed seeds necessitates strict processing and safety controls. Overall, R. communis emerges as a chemically versatile species with significant therapeutic and industrial potential, warranting further research into cultivar-specific chemistry, standardization of extraction and testing methods, and safe value-adding applications. Full article

Parkinson’s disease (PD) is a multisystem disorder in which gastrointestinal dysfunction often precedes motor symptoms, yet the molecular links between peripheral stress and central neurodegeneration remain unclear. We investigated whether genes commonly dysregulated in PD and a classic model of intestinal inflammation (IBD) might reveal conserved stress-responsive molecules relevant to brain pathology. Shared gene signatures between PD and inflammatory bowel disease (IBD) were identified from peripheral blood transcriptomes using weighted gene co-expression network analysis (WGCNA). Hub genes were prioritized via protein–protein interaction (PPI) analysis and evaluated for expression consistency in independent brain tissue transcriptomic datasets. Single-cell RNA sequencing (scRNA-seq) of the PD substantia nigra was used to define the cellular context of the key hub gene, and CellChat analysis assessed intercellular communication changes. Immunofluorescence validation was performed in an MPTP-induced PD mouse model. We identified 79 shared genes and 6 hub genes, among which only HSP90AA1 showed consistent upregulation across independent PD transcriptomic validation datasets. Functional enrichment highlighted inflammation-related pathways. Because peripheral immune infiltration showed only minor changes, we further investigated the cellular context of HSP90AA1 within the PD brain. ScRNA-seq analysis of the PD substantia nigra demonstrated that HSP90AA1 was expressed across multiple cell populations. Integration with transcriptional regulatory analysis identified TP53 as a potential upstream regulator, and the strongest TP53–HSP90AA1 co-expression and cellular colocalization signals were observed in astrocytes, prompting further astrocyte-focused investigation. CellChat analysis revealed altered intercellular communication patterns in PD substantia nigra, including changes in synapse-associated ligand–receptor interaction signatures, particularly involving NCAM-related pathways. In the MPTP-induced PD mouse model, immunofluorescence identified astrocytic HSP90α upregulation, and increased nuclear p53 signal in astrocytes, accompanied by dopaminergic neuron loss. Conclusion: Astrocytic upregulation of HSP90AA1 is associated with altered synapse-related intercellular communication patterns in the PD substantia nigra, potentially involving a predicted TP53 associated regulatory component. These findings, validated in an MPTP mouse model, identify HSP90AA1 as a candidate stress-responsive hub linking peripheral inflammatory states with astrocyte-associated molecular alterations in PD, providing a framework for further experimental investigation. Full article

Background: Malakoplakia is a rare chronic granulomatous inflammatory disorder characterized by defective macrophage phagolysosomal activity and accumulation of Michaelis–Gutmann bodies on histopathology. It occurs predominantly in immunocompromised individuals and may mimic infectious, inflammatory, or neoplastic processes, creating significant diagnostic challenges. We describe four cases of malakoplakia occurring in distinct immunocompromised states and review the published literature to better characterize its clinical spectrum, management, and outcomes. Methods: We conducted a retrospective case series of four patients diagnosed with histologically confirmed malakoplakia at our institution. Cases occurred in the setting of liver transplantation, kidney transplantation, relapsed acute myeloid leukemia, and ulcerative colitis treated with immunosuppressive therapy. A literature review was performed using PubMed and Google Scholar to identify published cases of malakoplakia in immunocompromised hosts. Demographic, clinical, microbiological, therapeutic, and outcome data were extracted and analyzed descriptively. Results: Four patients with malakoplakia involving the gastrointestinal tract or renal allograft were identified. Clinical presentations ranged from incidental endoscopic findings and tumor-like colonic masses to recurrent bacteremia and graft dysfunction. Histopathologic examination demonstrated characteristic Michaelis–Gutmann bodies in all cases. Management included antimicrobial therapy, observation, and surgical intervention when necessary. Two patients achieved complete clinical and histologic resolution, one required transplant nephrectomy because of persistent allograft infection, and one died from progressive acute myeloid leukemia. Combined with 48 cases identified in the literature, 52 patients were analyzed. The gastrointestinal tract was the most frequently affected site (76.9%), followed by the genitourinary tract (19.2%). Malignancy (32.7%), solid-organ transplantation (26.9%), and autoimmune disease (21.2%) were the most common underlying conditions. Conclusions: Malakoplakia should be considered in the differential diagnosis of mass lesions, persistent infections, and inflammatory lesions in immunocompromised patients, particularly those with malignancy or receiving immunosuppressive therapy. Early histopathologic diagnosis is essential to distinguish malakoplakia from malignancy and guide appropriate management. Our findings highlight the heterogeneous clinical manifestations and outcomes of this uncommon condition and emphasize the importance of multidisciplinary evaluation in affected patients. Full article

Inflammatory bowel diseases (IBDs), chronic inflammatory disorders of the gastrointestinal tract, are classified into Crohn’s disease (CD) and ulcerative colitis (UC). Despite differing clinical manifestations, both CD and UC share a common immunopathogenesis, involving excessive production of proinflammatory cytokines by macrophages and dendritic cells. Tumor necrosis factor-α (TNF-α), interleukin-12 (IL-12), and IL-23 are prototypical proinflammatory cytokines associated with CD and UC development, and biologics targeting these cytokines are widely used for treating patients with IBD. Antibodies (Abs) against IL-12 and IL-23 decrease intestinal inflammation by binding to the soluble forms of IL-12 and IL-23, respectively. Notably, anti-TNF-α Abs induce remission by neutralizing soluble TNF-α as well as membrane-bound TNF-α (mTNF-α). The binding of anti-TNF-α Abs to mTNF-α enables the diverse functions of IBD-specific TNF-α-inhibitors. Multiple modes of action of anti-TNF-α Abs for IBD include complement-dependent cytotoxicity, Ab-dependent cellular cytotoxicity, apoptosis of cells expressing mTNF-α, apoptosis of lamina propria T cells, and induction of regulatory T cells and macrophages. In this article, we introduce the diverse actions of anti-TNF-α Abs beyond TNF-α neutralization and discuss how these unique properties of anti-TNF-α Abs contribute to the efficient downregulation of IBD-associated inflammation. Full article

Histamine plays an essential role in gastrointestinal physiology and immune control, while its balance in the intestinal environment is largely maintained through degradation by diamine oxidase (DAO), a copper-dependent enzyme mainly produced by differentiated enterocytes. Impaired DAO activity reduces the intestinal barrier to luminal histamine, leading to increased local and systemic exposure and contributing to altered motility, permeability, visceral sensitivity, and immune activation. Accumulating research suggests that disturbances in diamine oxidase regulation contribute to the development of various gastrointestinal diseases, including histamine intolerance, inflammatory and functional bowel disorders, intestinal ischemia, and liver pathology. This review summarizes current knowledge on the biochemistry, localization, and regulation of DAO, as well as histamine signalling via H1–H4 receptors in the gastrointestinal tract. We highlight the interaction between epithelial injury, immune activation, dysbiosis, and histamine accumulation, and discuss the divergent interpretation of mucosal versus circulating DAO activity. Finally, we critically assess the diagnostic limitations of serum DAO and explore emerging therapeutic strategies targeting impaired histamine degradation. Although DAO represents a promising adjunctive biomarker and therapeutic target, its clinical utility requires standardized measurement methods and integrative diagnostic approaches. Full article

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that arises from a complex interplay of genetic susceptibility, immune dysregulation, environmental exposures, and altered host–microbiome interactions. Increasing evidence identifies the gut microbiota as a central component of IBD pathogenesis. In healthy individuals, the intestinal microbiota supports epithelial integrity, metabolic homeostasis, immune education, colonization resistance, and bidirectional gut–brain communication. In IBD, this ecosystem is disrupted by reduced microbial diversity, expansion of pathobionts, and broader functional alterations affecting community stability and metabolic output. Importantly, these changes are increasingly viewed not merely as consequences of inflammation, but as active contributors to disease development and persistence. Dysbiosis may also influence neuroimmune signaling through the gut–brain axis, linking microbial metabolites, intestinal barrier dysfunction, enteric nervous system activity, and psychological comorbidities frequently observed in patients with IBD. This review provides a comprehensive overview of the role of the gut microbiota in IBD, beginning with its physiological functions in intestinal homeostasis and the evidence linking dysbiosis to disease pathogenesis, followed by a critical evaluation of current microbiome-based therapeutic strategies, their translational challenges, and prospects for personalized microbiota-directed interventions. Approaches such as fecal microbiota transplantation (FMT), probiotics, live biotherapeutic products, and genetically engineered bacteria aim to restore microbial balance and modulate intestinal inflammation. Among these, FMT has provided the strongest proof-of-concept for microbiome restoration, whereas probiotic efficacy remains variable and strain-dependent. Emerging defined microbial consortia and engineered bacterial platforms offer improved standardization and mechanistic precision, but their clinical application remains limited by challenges related to engraftment, durability of response, safety, and treatment optimization. Collectively, current evidence supports gut microbiota as both a key determinant of IBD pathogenesis and a promising therapeutic target, underscoring the need for more precise and personalized microbiota-directed approaches in IBD management. Full article

The development of patient-derived organoids (PDOs) has substantially advanced the study of gastrointestinal diseases by providing three-dimensional human models that faithfully recapitulate the structural, molecular, and functional characteristics of native tissues. Unlike conventional two-dimensional cultures and animal models, intestinal organoids preserve epithelial architecture, cellular heterogeneity, and patient-specific genetic features, enabling more physiologically relevant investigations of gastrointestinal physiology and disease. Recent technological advances, including co-culture systems, organoid-derived monolayers, and organ-on-chip platforms, have further expanded their ability to model epithelial interactions with immune cells, stromal components, and the gut microbiota. These developments have facilitated mechanistic studies of epithelial barrier function, host–microbiota communication, microbial metabolites, and endocrine signaling, while also supporting translational applications in inflammatory bowel disease, infectious disorders, inherited gastrointestinal diseases, and gastrointestinal cancers. Moreover, patient-derived organoids have emerged as promising platforms for drug screening, biomarker discovery, precision medicine, and regenerative therapies. Despite these advances, several challenges remain, including limited representation of the native tissue microenvironment, lack of standardized culture protocols, scalability, and regulatory issues that currently restrict routine clinical implementation. This review summarizes recent progress in gastrointestinal organoid technology, highlighting current applications, emerging experimental platforms, and future perspectives for integrating organoid-based models into translational research and personalized medicine. Full article

Eosinophils are tissue-adapted granulocytes with important roles in host defense, immune regulation, barrier responses, and inflammatory disease. Beyond classical degranulation, activated eosinophils can release eosinophil extracellular traps (EETs), extracellular DNA and protein structures that arise through cytolytic nuclear EETosis or rapid mitochondrial DNA (mtDNA) release. These traps may contribute to host protection by immobilizing pathogens and concentrating eosinophil granule proteins at sites of mucosal or tissue inflammation. However, when EET formation is excessive, persistent, or insufficiently cleared, the same structures may promote epithelial injury, mucus viscosity, thromboinflammation, tissue remodeling, fibrosis, and chronic eosinophilic inflammation. This review summarizes the cellular mechanisms, structural organization, inducing stimuli, and disease relevance of EETs. Particular attention is given to infectious settings, eosinophilic airway and middle-ear disease, systemic vasculitic and hypereosinophilic disorders, inflammatory skin and ocular diseases, eosinophilic gastrointestinal disease, and cancer. Current evidence indicates that EETs should be interpreted as context-dependent eosinophil effector structures with dual biological potential. Although their mechanistic relevance is increasingly recognized, further histological, functional, and clinical validation is needed before EETs can be established as reliable biomarkers or therapeutic targets. Full article

Chronic constipation is a prevalent functional gastrointestinal disorder with limited long-term treatment options. This study examined whether a fucoidan preparation derived from Sargassum fusiforme (SF) ameliorates loperamide (LOP)-induced constipation in male ICR mice. SF was administered by oral gavage at 50, 100 or 200 mg/kg/day for 35 days, and constipation was induced with LOP (5 mg/kg) during the final 7 days; the design is therefore preventive rather than therapeutic. Defecation endpoints were recorded at the cage level (n = 3 cages per group) and fecal moisture in individual mice (n = 7 per group), whereas colonic cytokine and myeloperoxidase (MPO) measurements (n = 3–4 per group) and Western blot analyses (n = 3 per group) were performed in a small subset of animals, and histological analyses in n = 6–8 per group. SF increased fecal output and fecal moisture content with increasing dose; at 200 mg/kg the relative fecal number returned to the level of the Vehicle control group, although the absolute daily pellet count remained lower than that of the Vehicle control and of the Positive control group. SF administration was associated with lower colonic TNF-α, IL-6, IL-1β and MPO concentrations, with reduced phosphorylation of p38, JNK and ERK, with higher C-kit and stem cell factor (SCF) levels, with normalization of the LOP-induced increase in aquaporin-3 (AQP3), and with recovery of colonic mucosal thickness and mucin content. 16S rRNA gene sequencing showed a shift in fecal microbiota community structure (PERMANOVA p = 0.0002) and a dose-related increase in the combined relative abundance of Lactobacillus and Bifidobacterium, without a reduction in alpha diversity. These findings indicate that SF ameliorates LOP-induced constipation in male mice and that this effect is accompanied by changes in colonic inflammatory signaling, motility-related protein expression, mucosal architecture and gut microbiota composition. Full article

Gut lactic acid bacteria are emerging as potential targets for modulating host purine metabolism and alleviating hyperuricemia-related disorders. This study aimed to isolate purine-degrading lactic acid bacterial strains from porcine intestine and systematically evaluate their probiotic potential through both in vitro and in vivo approaches. A strain designated Pedio6-1 was isolated and identified as Pediococcus acidilactici based on 16S rRNA sequencing. In vitro assays demonstrated that P. acidilactici Pedio6-1 exhibited nearly complete adenine clearance (approaching 100%) and a total purine clearance rate of 30.73%, along with strong tolerance to acidic conditions, bile salts, and gastrointestinal enzymes. To further assess its in vivo efficacy, a high-fat diet-induced obese mouse model was employed. After 8 weeks of intervention, Pedio6-1 supplementation significantly reduced the final body weight and liver index, and markedly decreased hepatic guanine levels (p < 0.05), with a trend toward lower total purine content compared to the obese control group. Mechanistically, Pedio6-1 treatment significantly downregulated the hepatic mRNA expression of pro-inflammatory cytokines IL-1β and TLR4 (p < 0.05). Serum untargeted metabolomics revealed that Pedio6-1 treatment shifted the metabolic profile toward that of normal diet-fed mice, with differential pathways predominantly enriched in porphyrin metabolism and amino acid biosynthesis and metabolism. Notably, key metabolites with antioxidant and metabolic regulatory functions, including bilirubin, biliverdin, glutathione, citrate, L-cystathionine, and 4-pyridoxic acid, were significantly elevated following treatment, while N-acetylornithine and methylmalonate ester were decreased, indicating coordinated remodeling of oxidative stress defense, vitamin B6 homeostasis, and energy metabolism. Collectively, these findings indicate that Pedio6-1 not only possesses direct purine-degrading activity in vitro, but also ameliorates purine metabolic disturbances, inflammation, and oxidative stress in obese mice, likely through the modulation of porphyrin and amino acid metabolic pathways, highlighting its promise as a functional probiotic candidate for managing obesity-associated purine metabolic disorders. Full article

Background: Eosinophilic jejuno-duodenitis is a rare inflammatory disorder characterized by eosinophilic infiltration of the gastrointestinal tract, with highly variable clinical presentations. Mucosal eosinophilic duodenitis and jejunitis associated with ascites is uncommon and may mimic inflammatory or neoplastic conditions. Case Presentation: A 26-year-old male presented with persistent left-sided abdominal pain without bowel habit changes. Laboratory investigations revealed only slight inflammatory syndrome and peripheral eosinophilia. Contrast-enhanced abdominopelvic computed tomography demonstrated minimal ascites and circumferential wall thickening with contrast enhancement of duodenal and jejunal loops in the left flank. Given the nonspecific imaging findings, differential diagnoses included Crohn’s disease, intestinal lymphoma, and infectious enteritis. Endoscopic evaluation with histopathological analysis confirmed dense eosinophilic infiltration of the duodenal and jejunal mucosa, establishing the diagnosis of eosinophilic jejuno-duodenitis after exclusion of secondary causes. Management and Outcome: The patient was treated with budesonide, with rapid clinical improvement and resolution of inflammatory markers. Follow-up magnetic resonance enterography performed three months after initiation of treatment demonstrated complete resolution of bowel wall thickening and disappearance of the minimal ascites. Conclusions: Eosinophilic jejuno-duodenitis should be considered in young patients presenting with small bowel thickening, ascites, and peripheral eosinophilia. Awareness of this entity is essential to avoid misdiagnosis and unnecessary invasive procedures. Full article

(1) Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain and altered bowel habits, linked to dysbiosis and inflammation. Currently available treatments, focused on symptom management, displayed limited efficacy. Recent research highlights microbiota modulation as a potential therapeutic strategy to restore intestinal barrier integrity; (2) A dextran sulfate sodium (DSS)-induced mouse model of post-colitis IBS-like symptoms was performed to evaluate the effect of a novel mixture of Enterococcus lactis SF68^®, butyrate, and folate. Disease activity index and spleen weight were assessed. Markers of gut inflammation, intestinal barrier alterations, and gut butyrate bioavailability were measured. The activity of colonic mitochondria was also analyzed; (3) Supplementation with the novel mixture significantly reduced spleen weight and cytokine levels. The intestinal epithelial barrier was restored through an increase in claudin-1, occludin, and defensin 1–3 and a reduction in LBP plasma level. Treatment with the mixture enhanced the expression of butyrate transporters in mice. Mitochondrial activity markers, including citrate synthase and Cytochrome c oxidase, were improved by treatment; (4) The novel mixture containing Enterococcus lactis, butyrate, and folate exerted a protective effect against post-inflammatory IBS by reducing local inflammation, restoring intestinal barrier integrity, and enhancing butyrate bioavailability, suggesting its potential for managing post-inflammatory IBS symptoms effectively. Full article