Search Results (3,107)

Bovine colostrum stands out as a natural supplement with rich bioactive components that attract attention for its therapeutic potential in the maintenance and improvement of gastrointestinal (GI) health. The major bioactive components of bovine colostrum include immunoglobulin (Ig) (especially immunoglobulin G), lactoferrin (LF), growth Factors (IGF-I, TGF-β, EGF), oligosaccharides (OS), and bioactive peptides. These components play a role in epithelial repair, suppression of inflammation, balancing the microbiota, and enhancing the mucosal barrier. Various animal models and recent human studies show that bovine colostrum has various positive effects against gastrointestinal tract diseases such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), non-steroidal anti-Inflammatory drug (NSAID)-induced enteropathy, and necrotizing enterocolitis (NEC). These effects include preservation of epithelial integrity, reduction of inflammatory markers, and improvement of intestinal permeability. Studies on the tolerability and efficacy profiles of various bovine colostrum formulations for oral, oropharyngeal, and enteral administration are increasing. In this review, the multifaceted effects of bovine colostrum on the gastrointestinal tract are explained at a mechanistic level, and potential areas of study for clinical translation are presented. Bovine Colostrum stands out as a promising natural biotherapeutic agent for both preventive and therapeutic approaches. Full article

Inflammatory bowel diseases (IBDs) encompass Crohn’s disease and ulcerative colitis. They represent idiopathic and chronic inflammatory conditions. Mucosal immune dysfunction and compromised gastrointestinal barrier integrity are implicated in the pathophysiological mechanisms of inflammatory bowel diseases. Recent studies have identified endothelial dysfunction as a pivotal mediator in IBD pathogenesis. Through multiple cellular and molecular interactions, endothelial dysfunction orchestrates inflammatory responses. Objectives: This systematic review examines contemporary evidence (2019–2025), emphasising the role of endothelial dysfunction in intestinal inflammation mechanisms, focusing on vascular-epithelial crosstalk, molecular signalling pathways, and therapeutic implications. Methods and results: A comprehensive literature search was conducted using PubMed, Google Scholar, Europe PMC and DOAJ databases, focusing on peer-reviewed articles published between 2019 and 2025. Following the database search and screening process, a total of 53 studies met the eligible criteria and were included in the final analysis. Keywords included “endothelial dysfunction,” “inflammatory bowel disease,” “gut-vascular barrier,” “nitric oxide,” and “intestinal inflammation.” Contemporary research demonstrates that endothelial dysfunction in IBD manifests through decreased nitric oxide bioavailability, enhanced oxidative stress, aberrant cytokine networks, pathological angiogenesis, and compromised gut-vascular barrier integrity. The emerging concept of dual barrier dysfunction highlights the interdependent relationship between epithelial and endothelial barriers in maintaining intestinal homeostasis. Conclusions: Offering novel therapeutic targets for precision medicine approaches, endothelial dysfunction represents a central driver in the pathophysiological mechanism in IBD. Understanding vascular-epithelial interactions provides fundamental insights for developing targeted interventions to restore intestinal barrier function and resolve chronic inflammation. Full article

Background: Ulcerative colitis (UC), a chronic and relapsing form of inflammatory bowel disease (IBD), arises from a multifactorial interplay of genetic predisposition, immune dysregulation, and environmental triggers. Despite advances in understanding UC pathogenesis, the identification of reliable biomarkers and key regulatory genes remains essential for unraveling disease mechanisms. Such insights are crucial for improving diagnostic precision and developing personalized therapeutic strategies. Methods: In this study, gene expression profiles from publicly available microarray and RNA-sequencing datasets were systematically analyzed using advanced bioinformatics tools. Differentially expressed genes (DEGs) were identified through statistical comparisons, and functional enrichment analyses were performed to explore their biological relevance. A total of 141 overlapping DEGs were extracted from three GEO datasets, and 20 key DEGs were further prioritized via protein–protein interaction (PPI) network construction. Hub genes, relevant signaling pathways, associated transcription factors (TFs), and microRNAs (miRNAs) linked to disease progression were identified. Potential therapeutic compounds were also predicted through computational drug–gene interaction analysis. Results: The analysis revealed a panel of novel biomarkers-TLR2, IFNG, CD163, CXCL9, CCL4, PRF1, TLR8, ARG1, LILRB2, FPR2, and PPARG-that function as key hub genes implicated in ulcerative colitis (UC) pathogenesis. These genes were associated with critical biological processes including signal transduction, inflammatory and immune responses, proteolysis, lipid transport, and cholesterol/triglyceride homeostasis. Furthermore, transcription factors (FOXC1, GABPA, GATA2, SUPT5H) and microRNAs (hsa-miR-34a-5p, hsa-miR-335-5p, hsa-miR-24-3p, hsa-miR-23a-5p, hsa-miR-26a-5p) revealed key regulatory networks influencing post-transcriptional gene regulation. Molecular docking analysis predicted Apremilast and Golotimod as promising therapeutic candidates for UC intervention. Conclusions: In conclusion, this study enhances our understanding of ulcerative colitis pathogenesis by identifying key biomarkers and therapeutic targets, paving the way for future advancements in personalized diagnosis and treatment strategies. Full article

Background: The interaction between probiotics and the vitamin D/vitamin D receptor (VDR) pathway has been increasingly explored as a potential mechanism for immune modulation in inflammatory bowel disease (IBD). Lactobacillus rhamnosus GG (LGG) has shown promising results in ulcerative colitis (UC) patients, but its effect on the VDR pathway remains unexplored in humans. Aim: To test the hypothesis that LGG can stimulate the vitamin D/VDR pathway and modulate mucosal-adherent microbiota. Methods: In this study, we analyzed a subgroup of 13 patients from the LGGinUC trial, in which UC patients with mild-to-moderate disease activity received LGG monotherapy for four weeks. Colonic biopsy samples were collected before and after treatment to evaluate VDR expression via RT-qPCR and immunohistochemistry. Mucosal-adherent microbiota was also analyzed by DNA extraction and next-generation sequencing (NGS). Results: LGG administration significantly increased VDR mRNA expression in colonic mucosa (p < 0.05), with a corresponding rise in VDR protein levels in both epithelial and sub-epithelial compartments. Microbiota analysis revealed a reduction in α-diversity, primarily due to a decrease in commensal bacterial species, while β-diversity remained largely unchanged. Conclusions: Although the present results have to be considered preliminary, this is the first human study demonstrating that probiotic supplementation can upregulate VDR expression in colonic mucosa. We propose that LGG may exert its beneficial effects in UC by stimulating the VDR pathway, which in turn modulates mucosal immunity and microbiota composition. Further studies with larger sample sizes and longer treatment durations are needed to validate these findings and explore their therapeutic implications. Full article

Archaea, one of the three domains of life, are increasingly recognized as consistent, though often underappreciated, members of the human microbiome, yet their roles in health and disease remain poorly understood. Unlike bacteria, no archaeal species have been conclusively identified as primary mammalian pathogens, but their widespread presence across diverse body sites suggests potential indirect contributions to host physiology and pathology. Current evidence is synthesized on archaeal diversity and habitat specificity across multiple human-associated sites, encompassing the gastrointestinal, aerodigestive, and urogenital tracts as well as the skin. Methanogens dominate the lower gastrointestinal tract (LGT), where they influence fermentation dynamics and methane production, while members of the class Nitrososphaeria are prevalent on the skin and upper aerodigestive tract (UAT), reflecting ecological specialization. Variability in archaeal composition across niches highlights possible links to disease processes: methanogens have been associated with irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), obesity, and colorectal cancer (CRC); Methanobrevibacter oralis is enriched in periodontal disease; and archaea have been detected in the lungs of cystic fibrosis patients. Although archaea lack canonical bacterial virulence factors, they may contribute indirectly through metabolic cross-feeding, immune modulation, synergy in polymicrobial infections, and alteration of host–microbiome network dynamics. This review explores the emerging concept of the human “archaeome”, evaluates current evidence for archaeal involvement in disease, and highlights emerging technologies, such as bacteria-MERFISH and multi-omics profiling, that enable translational applications including microbiome diagnostics, therapeutic targeting, and microbiome engineering. Full article

Comprising multiple microorganisms, the microbiota plays a crucial role in regulating the immune system and maintaining homeostasis. The influence of genetic and environmental factors causes the composition of the microbiota to change throughout life, which is called the plasticity of the microbiota. A eubiotic microbiota promotes the immune response, reducing the risk of inflammation and diseases such as IBD and cancer. The Mediterranean diet is of fundamental importance for a healthy microbiota. On the contrary, Western diets lead to microbiota dysbiosis and inflammation. Microalgae, and, in particular, their derivatives, show promise and relevance in the search for potential anti-inflammatory and antioxidant biomolecules. This review focuses on the correlation between microbiota, nutrition, immunity and microalgal derivatives, highlighting how these may be a potential innovative therapeutic strategy for the management of chronic inflammatory diseases. Full article

The pathogenesis of Inflammatory Bowel Disease is complex and not completely understood, resulting from multifactorial interactions between genetic predisposition, environmental triggers, and dysregulation of both innate and adaptive immune responses. Cytokines, produced by dysregulated immune cells, trigger chronic intestinal inflammation leading to tissue damage, carcinogenesis, and disease perpetuation. Current advanced therapies—including tumor necrosis factor (TNF)-α antagonists, adhesion and trafficking inhibitors (such as anti-integrin agents and sphingosine-1-phosphate receptor modulators), interleukin inhibitors, and Janus kinase inhibitors—have improved patient outcomes, but targeting a single inflammatory pathway is often insufficient for long-term disease control. To further improve therapeutic efficacy, novel approaches are under investigation, including advanced combination therapies that simultaneously inhibit multiple pro-inflammatory pathways and microbiome-based treatments to restore intestinal homeostasis. In this evolving therapeutic scenario, precision medicine and advanced combination therapies appear promising for breaking through the current therapeutic ceiling. This review highlights current knowledge on the role of cytokines in IBD pathogenesis and explores how their modulation can modify and control disease course. Full article

Natural bioactive chemicals sourced from marine species have attracted growing interest due to their immunomodulatory, antioxidant, and gut microbiota-regulating characteristics. These chemicals, especially peptides, offer therapeutic approaches for addressing inflammation, immunological dysfunction, and intestinal barrier disturbance, which are frequently observed in conditions such as inflammatory bowel disease (IBD). This review centers on current discoveries about marine-derived peptides from octopus, sea conch, and scallop. These substances have demonstrated a considerable ability to restore intestinal integrity, regulate immune cell function, reduce pro-inflammatory cytokines, and rebalance dysbiotic gut microbiota. We consider several in vivo scenarios, encompassing dextran sulphate sodium (DDS)-induced colitis and cyclophosphamide-induced immunosuppression. These compounds raise the expression of tight junction proteins (including ZO-1 and occludin), boost the production of mucin, and encourage the growth of good bacteria such as Lactobacillus and Lachnospiraceae. Their effects are mechanistically associated with the inhibition of critical inflammatory pathways (e.g., Nuclear factor-κB (NF-κB), Toll-like receptor 4 (TLR-4)) and the modulation of both innate and adaptive immune responses. These versatile bioactives can serve as dietary supplements or complementary therapies for gastrointestinal and cancer-related issues. This review emphasizes the therapeutic potential of marine peptides, concentrating on gut–immune–microbiota interactions, as well as exploring future avenues for clinical translation and drug development Full article

Background/Objectives: Because of the chronic course of the disease, clinicians managing IBD frequently encounter patients with a prior or newly diagnosed cancer. This can be related to the specific background cancer risk in that subject, aging, familial/genetic factors, or ongoing chronic inflammation. However, a potential influence of some therapeutic agents should also be considered. This setting, in the absence of controlled trials and few open series reports available, raises issues such as correct screening, prevention, and surveillance, but also eventual modification or adaptation of the medical management. Methods and Results: Few consensus guidelines and studies are available on the management of IBD patients with a history of cancer, and therefore, we aim to review the recommendations of the current guidelines and the evidence reported in the most recent real-world cohorts. Conclusions: This review will offer (a) an understanding of the background of cancer risk in IBD patients; (b) analysis and discussion of the risk of cancer related to IBD therapy; and, finally, (c) some clues for the management of IBD in patients with a previous or current history of cancer. Full article

Inflammatory bowel disease commonly requires advanced therapies to induce and maintain durable remission. Sphingosine-1-phosphate receptor modulators are the latest class of orally administered small molecules that have been added to the therapeutic armamentarium for inflammatory bowel disease. These molecules reduce inflammation by sequestering lymphocytes in lymph nodes, thereby reducing immune cell trafficking to the gut. Etrasimod and ozanimod are both licensed for moderate-to-severe ulcerative colitis and have both shown superiority over placebo, with emerging data for their use in Crohn’s disease. By modulating immune cell distribution, without reducing overall immune function, they offer a highly favourable safety profile. This narrative review explores the pharmacology, safety and efficacy of sphingosine-1-phosphate receptor modulators based on clinical trials and real-world evidence and offers practical guidance on their initiation and monitoring. Full article

Inflammatory bowel disease (IBD) is a multifactorial and complex condition of the gastrointestinal tract shaped by host genetics, immune dysregulation, gut microbiota and environmental determinants, with a steadily rising global prevalence. Although the etiology of IBD remains incompletely understood, chronic inflammation accompanied by oxidative stress, immune dysregulation, and gut dysbiosis is widely recognized as a hallmark of the condition. Given the frequent occurrence of undernutrition in IBD patients, the role of vitamins and micronutrients in modulating disease activity has been recently explored. Selenium (Se) is universally recognized as an essential trace element due to its diverse physiological functions, including potent antioxidant activity, anti-inflammatory effects, immunomodulatory properties, and the ability to influence gut microbial composition and diversity. This comprehensive review examines current evidence on the relationship between Se status and IBD, integrating epidemiological and experimental findings, elucidating the underlying biological mechanisms, and introducing Se nanoparticles, a viable therapeutic option using Se in IBD management. Full article

Background: Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder with limited treatment options. Emerging evidence reveals bidirectional crosstalk between gut and brain through inflammatory signaling, leading us to hypothesize that anti-neuroinflammatory agents may concurrently ameliorate intestinal inflammation. The scorpion venom-derived heat-resistant synthetic peptide (SVHRSP), a bioactive peptide initially identified in scorpion venom and subsequently synthesized by our laboratory, possesses neuroprotective, anti-inflammatory, and antioxidative activities. Its properties make SVHRSP a promising candidate for investigating the therapeutic potential of anti-neuroinflammatory strategies in mitigating intestinal inflammation. Methods: Using a chronic dextran sodium sulfate (DSS)-induced colitis model in wild-type and α7 nicotinic acetylcholine receptor (α7nAChR) knockout mice, along with lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, we assessed SVHRSP’s effects on inflammation, histopathology, gut permeability, oxidative stress markers, and α7nAChR-Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling. Results: SVHRSP treatment significantly ameliorated colitis symptoms in wild-type mice by reducing inflammation, repairing histological damage, restoring gut barrier function, and attenuating oxidative stress, with these effects abolished in α7nAChR knockout mice. Mechanistically, SVHRSP activated JAK2/STAT3 signaling through α7nAChR engagement, suppressing proinflammatory cytokine production in macrophages. Conclusion: These results demonstrated that SVHRSP alleviated intestinal inflammation via α7nAChR-dependent JAK2/STAT3 activation. Combined with its known neuroprotective properties, our findings support the repurposing of this neuroactive peptide, SVHRSP, for treating intestinal inflammatory disorders. Full article

Background: Opioid use is common among patients hospitalized for inflammatory bowel disease (IBD) exacerbation and has been associated with an increased risk of readmissions. Prior studies, however, have mostly limited their analysis to hospital opioid use. This study examines opioid exposure and dosing before, during, and after hospitalization and its impact on 30- and 90-day hospital readmissions. Methods: We reviewed all adults admitted for an IBD exacerbation from 1 January 2016 to 3 January 2020, excluding pregnant patients and those with an IBD-related surgery. Use and dose of opioids before and during hospitalization and at discharge were identified through manual chart review. IBD type, demographics, and comorbidities were defined. The associations between opioid use characteristics and readmission were assessed using a series of multivariable logistic regression models. Results: Among 1062 patients meeting inclusion criteria, 191 (18.0%) were readmitted within 30 days of their index hospitalization, and 285 (26.8%) were readmitted within 90 days. Of these 1062 patients, 96 (9.02%) had preadmission opioid use, 340 (31.95%) had inpatient use, and 133 (12.50%) received a discharge opioid prescription. Preadmission, inpatient, and discharge opioid use were not associated with 30-day readmission. Preadmission and inpatient opioid use were also not associated with 90-day readmission; however, a prescription for an opioid at discharge was associated with 90-day readmission even after adjusting for confounders, OR 1.86 (1.27, 2.75), p = 0.002. On multivariable analysis, we also found that higher maximum daily dose of discharge opioids, OR 1.01 (1.00, 1.02), p = 0.037, was found to be associated with 30-day readmissions, and higher opioid doses preadmission, OR 1.01 (1.00, 1.03), p = 0.029, and at hospital discharge, OR 1.01 (1.00, 1.02), p = 0.034, were associated with increased 90-day readmission. Conclusions: Opioid prescribing at discharge poses a significant risk for readmissions. Discharge planning should emphasize minimal use of opioids at discharge. Full article

Background: Tumor necrosis factor-alpha (TNF-α) serves as a central mediator of inflammation and represents key therapeutic target in inflammatory bowel disease (IBD). This study investigates the protective effects of salidroside (Sal) against inflammation and explores its underlying molecular mechanisms. Methods: We employed network pharmacology to identify potential targets of Sal. The anti-inflammatory effects of Sal were evaluated in LPS-Induced cellular models using NCM460 colonic epithelial cells and RAW264.7 macrophages, as well as in a murine model of acute colonic inflammation. Direct target engagement was confirmed through cellular thermal shift assay (CETSA) and co-immunoprecipitation (Co-IP). The mechanism was further elucidated via site-directed mutagenesis and analysis of the IKK/NF-κB signaling pathway. Results: Network pharmacology predicted TNF-α as a key target. Sal significantly attenuated LPS-Induced inflammation in vitro and ameliorated colitis symptoms in vivo. Notably, CETSA and Co-IP assays confirmed direct interaction between Sal and TNF-α. Mutagenesis studies identified Arg179, Lys188, and Tyr191 as critical residues for this binding. Mechanistically, Sal inhibited TNF-α-mediated activation of the IKK/NF-κB pathway and the subsequent production of pro-inflammatory cytokines. Conclusion: Our findings demonstrate that Sal alleviates inflammation by directly binding to TNF-α and suppressing the downstream NF-κB signaling cascade, thereby positioning it as a promising therapeutic candidate for TNF-α-driven inflammatory diseases. Full article

Background: Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn’s disease (CD), is characterized by chronic intestinal inflammation with fluctuating clinical severity. Although fecal calprotectin (FC) and fecal occult blood (FOBT) are established noninvasive biomarkers of intestinal inflammation, their interplay with nutritional status and disease activity has not been fully elucidated. This study aimed to explore the relationship between FC, FOBT, and disease activity in IBD, and to assess the potential mediating role of nutritional status as measured by the prognostic nutritional index (PNI). Methods: This retrospective study includes 128 adult patients with confirmed IBD (50 UC and 78 CD) examined at a tertiary care center between December 2023 and August 2025. Disease activity was assessed using the Mayo score for UC and the Harvey–Bradshaw Index for CD. FC levels were quantitatively measured using an enzyme-linked immunosorbent assay (ELISA), and fecal occult blood testing was performed with an automated latex agglutination-based system. Multivariable linear regression models were conducted to identify independent predictors of disease activity. Results: UC patients had significantly higher FC levels (278.0 vs. 133.5 µg/g, p < 0.001), FOBT positivity rates (76.7% vs. 43.6%, p = 0.002), and lower PNI (49.2 ± 4.2 vs. 51.5 ± 4.6, p = 0.048) compared to CD patients. In both UC and CD, disease activity scores were positively correlated with FC, FOBT positivity, CRP, and duration of illness, and negatively correlated with PNI (p < 0.05). In multivariable regression, PNI lost predictive value when FC and FOBT were included; FC and FOBT remained strong independent predictors of disease activity. Conclusions: FC and fecal occult blood are independently associated with higher disease activity in IBD, and may mediate the observed relationship between poor nutritional status and inflammation severity. The loss of significance of PNI in adjusted models suggests that intestinal inflammation and bleeding may act as intermediaries linking malnutrition to disease activity. Full article