Search Results (88)

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

Since colonic dopamine levels are markedly reduced during inflammatory bowel disease (IBD), we investigated how dopamine affects regulatory T-cells (Treg), which critically limit gut inflammation. Previously, we showed that the stimulation of the high-affinity dopamine receptor D₃ (Drd3) impairs suppressive Treg activity and limits their recruitment into the colon upon gut inflammation. Here we study the role of the low-affinity dopamine receptor Drd2 in Treg. We find that mice harbouring Drd2-deficient T-cells developed more severe colitis induced by dextran sodium sulphate. The stimulation of Drd2 potentiated the suppressive Treg activity and increased their ability to reach the colonic tissue. A transcriptomic analysis of intestinal mucosa from IBD patients revealed an association with increased DRD3 and reduced DRD2 expression. Bioluminescence resonance energy transfer assays revealed that Drd2 and Drd3 form a heteromer. An in situ proximity ligation assay indicated that the Drd2:Drd3 heteromer was expressed on colonic Treg, and its expression was increased upon inflammation. Using peptides analogous to the transmembrane (TM) segments from Drd2 and Drd3 in bimolecular fluorescence complementation assays, we found TM peptides able to disassemble this heteromer. The heteromer disassembly dampened the suppressive Treg activity and impaired the recruitment of Treg into the colon upon inflammation. Our findings indicate that the Drd2:Drd3 heteromer constitutes a dopamine sensor that regulates suppressive Treg activity and their colonic recruitment. Full article

Current therapies for inflammatory bowel disease (IBD), such as olsalazine and cyclosporine, often exhibit limited long-term efficacy and are associated with adverse effects. Cannabidiol (CBD), a non-psychoactive phytocannabinoid, shows promise for its anti-inflammatory properties, though its effectiveness as a monotherapy remains inconclusive. This study investigates the therapeutic potential of combining low-dose CBD (10 mg/kg) with olsalazine (50 mg/kg) or cyclosporine (2.5, 5 mg/kg) in dextran sulphate sodium (DSS)-induced acute and chronic colitis models in mice. Disease severity was assessed via disease activity index (DAI), colon morphology, cytokine and chemokine expression, myeloperoxidase (MPO) activity, systemic inflammatory markers, and glucagon-like peptide-1 (GLP-1) regulation. Safety evaluations included haematology and plasma biochemistry. DSS-treated mice showed elevated DAI scores, colon shortening, heightened inflammation, and organ enlargement. Combination therapies significantly ameliorated colitis, reducing DAI, MPO activity, and inflammatory cytokines, while restoring colon length and GLP-1 levels—without inducing liver or kidney toxicity. These findings demonstrate that combining a low dose of CBD with standard IBD drugs enhances therapeutic efficacy while minimizing side effects, supporting its integration into future combination strategies for more effective and safer IBD management. Full article

Inflammatory bowel disease (IBD) results from genetic factors, environmental factors, and intestinal microbiota interactions. This study investigated the effects of Biombalance™ (BB) in dextran sulphate sodium (DSS)-induced colitis in mice. BB extract exhibits high antioxidant activity, as determined by DPPH and ORAC tests. Mice were fed a standard diet, and BB was administered by gavage for ten days, before administration of 2.75% DSS in drinking water. BB significantly protected mice against DSS effects, as assessed by colon length, disease activity index (DAI) scores and colonic pathological damage. In addition, BB inhibited the expression of proinflammatory markers, such as IL-6, IL-17, CXCL1 and TNF-α, and the inflammatory mediators iNOS, TGF-β, FoxP3 and F4/80, while increasing IL-10 expression in the colon. BB modified microbiota composition, attenuating the microbial diversity lost due to DSS, increasing beneficial bacteria like Muribaculum, Lactobacillus, Muscispirillum, Roseburia and Bifidobacterium, and decreasing potentially harmful bacteria such as Proteobacteria and Enterococcus. Interestingly, microbiota-predicted functions using PICRUSt revealed that BB extract increases the antioxidant superpathway of ubiquinol biosynthesis, including ubiquinol-7, 8, 9 and 10 (CoenzymesQ). These findings suggest that Biombalance™ administration may help to reduce gut inflammation and oxidation, at least partly through modifications of the microbiota and its metabolites. Full article

Combination of selenium (Se) and glutathione peroxidase (GPx) can reduce the dose of Se used while concurrently exploiting their antioxidative performance, which can be used as a potential treatment for ulcerative colitis. Nanozymes possess higher stability, are more economical, and have more multifunctionalities than natural enzymes and thus could be an ideal approach for their combination. Therefore, this study synthesised a nanozyme using glutathione (GSH) and Se—GSH-Se—and evaluated its alleviating effects on colitis in mice induced by dextran sulphate sodium salt (DSS). Three doses of GSH-Se, 6 mM, 12 mM, and 18 mM were supplemented in DSS-induced colitis in mice. Findings showed that GSH-Se supplementation ameliorated colitis by improving the colonic mucosal integrity, reducing inflammatory responses and oxidative stress, and alleviating gut microbiota imbalance in mice with DSS-induced colitis. Moreover, an in vitro experiment was performed to unravel the molecular mechanism by which GSH-Se ameliorated colitis in mice, based on lipopolysaccharide-induced inflammation in mouse colon epithelial cells. The results suggested that the alleviating effects of GSH-Se on mouse colitis was likely mediated by the activation of the Nrf2/Keap1 (nuclear factor E2-related factor 2/Kelch-like ECH-associated protein 1) and GPx4 signalling pathways. Full article

Background/Objectives: Current inflammatory bowel disease (IBD) treatments focus on symptomatic relief, highlighting the need for innovative approaches. Dysregulation of the cannabinoid 1 (CB1) receptor, part of the endocannabinoid system, is linked to colitis. While tetrahydrocannabinol (THC) alleviates colitis via CB1 activation, its psychotropic effects limit clinical use. ZCZ011, a CB1R allosteric modulator, and cannabidiol (CBD), a non-psychoactive cannabinoid, offer alternatives. This study investigated combining sub-therapeutic THC doses with ZCZ011 or CBD in a murine model of dextran sodium sulphate (DSS)-induced colitis. Methods: Acute colitis was induced with 4% DSS for 7 days, followed by 3 days of water. Chronic colitis was modelled over 24 days with alternating DSS concentrations. The combination of 2.5 mg/kg THC with 20 mg/kg ZCZ011 or 10 mg/kg CBD was evaluated. Key markers were assessed to determine efficacy and safety, including disease activity index (DAI), inflammation, cytokine levels, GLP-1, and organ health. Results: DSS-induced colitis resulted in increased DAI scores, cytokines, organ inflammation and dysregulation of GLP-1 and ammonia. THC at 10 mg/kg significantly improved colitis markers but was ineffective at 2.5 and 5 mg/kg. ZCZ011 alone showed transient effects. However, combining 2.5 mg/kg THC with either 20 mg/kg ZCZ011 or 10 mg/kg CBD significantly alleviated colitis markers, restored colon integrity and reestablished GLP-1 homeostasis. This combination also maintained favourable haematological and biochemical profiles, including a notable reduction in colitis-induced elevated ammonia levels. Conclusions: This study demonstrates the synergistic potential of low-dose THC combined with CBD or ZCZ011 as a novel, effective and safer therapeutic strategy for ulcerative colitis. Full article

Ulcerative colitis is a chronic relapsing–remitting and potentially progressive form of inflammatory bowel disease in which there is extensive inflammation and mucosal damage in the colon and rectum as a result of an abnormal immune response. MV130 is a mucosal-trained immunity-based vaccine used to prevent respiratory tract infections in various clinical settings. Additionally, MV130 may induce innate immune cells that acquire anti-inflammatory properties and promote tolerance, which could have important implications for chronic inflammatory diseases such as ulcerative colitis. This work demonstrated that the prophylactic administration of MV130 substantially mitigated colitis in a mouse model of acute colitis induced by dextran sulphate sodium. MV130 downregulated systemic and local inflammatory responses, maintained the integrity of the intestinal barrier by preserving the enterocyte layer and goblet cells, and reduced the oedema and fibrosis characteristic of the disease. Mechanistically, MV130 significantly reduced the infiltration of neutrophils and pro-inflammatory macrophages in the intestinal wall of the diseased animals and favoured the appearance of M2-polarised macrophages. These results suggest that MV130 might have therapeutic potential for the treatment of ulcerative colitis, reducing the risk of relapse and the progression of disease. Full article

Cannabinoids are emerging as promising treatments for inflammatory diseases such as ulcerative colitis. Specifically, cannabinoid 2 (CB2) receptors, which are upregulated during inflammation, have been distinctively linked to anti-inflammatory and analgesic effects. HU308, a synthetic cannabinoid developed to activate CB2 receptors selectively, aims to minimize unwanted off-target side effects. This study evaluated the effectiveness of both cannabidiol (CBD) and HU308 in mouse models of dextran sodium sulphate (DSS)-induced colitis, which mimic the acute and chronic phases of ulcerative colitis. Mice were treated with DSS in drinking water (four percent for the acute model and one to two percent for the chronic model) to induce colitis, as indicated by increased disease activity index (DAI) scores and inflammatory markers. Treatment with 60 mg/kg of CBD, but not lower doses, significantly reduced colitis symptoms, such as inflammation, cytokine levels, and MPO activity, while also normalizing glucagon-like peptide-1 (GLP-1) levels. HU308 showed comparable efficacy to high-dose CBD (60 mg/kg) but at a much lower dose (2.5 mg/kg), without observable toxicity. HU308 effectively normalized DAI scores, colon inflammation, ammonia levels, and GLP-1 expression in both colitis models. These results suggest that both CBD and HU308 are promising treatments for ulcerative colitis. However, HU308 demonstrates enhanced therapeutic potential by achieving similar outcomes at a fraction of the dose required for CBD, reducing the risk of off-target side effects. The ability of HU308 to modulate GLP-1, a biomarker of gut endocrine function, further underscores its promise as a novel treatment option. Full article

Background/Objectives: Cow’s milk allergy is one of the most common food allergies in children, and its pathomechanism is still under investigation. Recently, an increasing number of studies have linked food allergy to intestinal barrier dysfunction. The present study aimed to investigate changes in the intestinal microenvironment during the development of β-lactoglobulin (β-lg) allergy under conditions of early intestinal dysfunction. Methods: BALB/c mice received intraperitoneal β-lg with Freund’s adjuvant, followed by oral β-lg while receiving dextran sulphate sodium salt (DSS) in their drinking water (0.2% w/v). The immunized group without DSS and the groups receiving saline, oral β-lg, or DSS served as controls. Results: The study showed that the immunization effect was greater in mice with mild intestinal barrier dysfunction. Although DSS did not affect the mice’s humoral response to β-lg, in combination with β-lg, it significantly altered their cellular response, affecting the induction and distribution of T cells in the inductive and peripheral tissues and the activation of immune mediators. Administration of β-lg to sensitized mice receiving DSS increased disease activity index (DAI) scores and pro-inflammatory cytokine activity, altered the distribution of claudins and zonulin 1 (ZO-1) in the colonic tissue, and negatively affected the balance and activity of the gut microbiota. Conclusions: The research model used appears attractive for studying food allergen sensitization, particularly in relation to the initial events leading to mucosal inflammation and the development of food hypersensitivity. Full article

Acetate-producing Saccharomyces cerevisiae var. boulardii strains could exert improved effects on ulcerative colitis, which here, was preclinically evaluated in an acute dextran sodium sulphate induced model of colitis. Nine-week-old female mice were divided into 12 groups, receiving either drinking water or 2.75% dextran sodium sulphate for 7 days, combined with a daily gavage of various treatments with different levels of acetate accumulation: sham control (phosphate buffered saline, no acetate), non-probiotic control (Baker’s yeast, no acetate), probiotic control (Enterol^®, transient acetate), and additionally several Saccharomyces cerevisiae var. boulardii strains with respectively no, high, and extra-high acetate accumulation. Disease activity was monitored daily, and feces samples were collected at different timepoints. On day 14, the mice were sacrificed, upon which blood and colonic tissue were collected for analysis. Disease activity in inflamed mice was lower when treated with the high-acetate-producing strain compared to sham and non-probiotic controls. The non-acetate-producing strain showed higher disease activity compared to the acetate-producing strains. Accordingly, higher histologic inflammation was observed in non- or transient-acetate-producing strains compared to the sham control, whereas this increase was not observed for high- and extra-high-acetate-producing strains upon induction of inflammation. These anti-inflammatory findings were confirmed by transcriptomic analysis of differentially expressed genes. Moreover, only the strain with the highest acetate production was superior in maintaining a stable gut microbial alpha-diversity upon inflammation. These findings support new possibilities for acetate-mediated management of inflammation in inflammatory bowel disease by administrating high-acetate-producing Saccharomyces cerevisae var. boulardii strains. Full article

The enteric nervous system (ENS) interacts bidirectionally with the local immune system, responding to inflammation within the gastrointestinal (GI) tract. In a previous study using the same samples, several gene targets were identified as being differentially expressed in the inflamed colonic tissue of pigs challenged with dextran sodium sulphate (DSS). Additionally, animals in the basal DSS group, exhibited reduced growth and increased fecal and pathology scores, while the relative abundance of beneficial taxa was reduced and harmful bacteria increased. While changes in the innate immune response and barrier function are widely cited regarding inflammatory bowel disease (IBD), the effects of inflammation on the local structures of the enteric nervous system (ENS) are less well understood. Hence, the objectives of this study were to: (1) evaluate the expression of a range of functionally diverse neuroactive receptors, transporters and neurotrophic factors in RNA derived from the colonic tissue from the same pigs; (2) examine associations with these neuroactive components and inflammatory, barrier function and matrix remodeling targets. Mature pigs were split into two experimental groups: (1) basal diet (n = 10); (2) basal diet + DSS (n = 11). The pigs were orally challenged with DSS once daily for four days and sacrificed humanely. Colonic tissue was collected for gene expression analysis. Most of the targets evaluated in this study were present at low levels or in some cases were undetectable by QPCR, including the dopamine receptor DRD5 and the serotonin receptor HTR3A. The dopamine receptors (DRD1, DRD3, DRD4), serotonin receptor (HTR4), and other selected neuroactive receptors (GRM7, GABRA2) were down-regulated in the DSS-challenged animals relative to the basal group (p < 0.05). Most notably, DRD2, was up-regulated four-fold, suggesting an active process involving this receptor (p < 0.05). Relationships with (previously published) gene expression data from the same samples suggest that DRD1 and DRD2 are influenced by different pathways and may also be interlinked with matrix remodeling and, more specifically, genes relevant to the epithelial to mesenchymal transition (CDH1, CDH2, IL6, IL13, IL10, MMP1, MMP2) an important fibrotic process in the pathogenesis of IBD. Full article

The incidence of ulcerative colitis (UC) is increasing annually, and UC has a serious impact on patients’ lives. Polysaccharides have gained attention as potential drug candidates for treating ulcerative colitis (UC) in recent years. Huaier (Trametes robiniophila Murr) is a fungus that has been used clinically for more than 1000 years, and its bioactive polysaccharide components have been reported to possess immunomodulatory effects, antitumour potential, and renoprotective effects. In this study, we aimed to examine the protective effects and mechanisms of Huaier polysaccharide (HP) against UC. Based on the H₂O₂-induced oxidative stress model in HT-29 cells and the dextran sulphate sodium salt (DSS)-induced UC model, we demonstrated that Huaier polysaccharides significantly alleviated DSS-induced colitis (weight loss, elevated disease activity index (DAI) scores, and colonic shortening). In addition, HP inhibited oxidative stress and inflammation and alleviated DSS-induced intestinal barrier damage. It also significantly promoted the expression of the mucin Muc2. Furthermore, HP reduced the abundance of harmful bacteria Escherichia-Shigella and promoted the abundance of beneficial bacteria Muribaculaceae_unclassified, Anaerotruncus, and Ruminococcaceae_unclassified to regulate the intestinal flora disturbance caused by DSS. Nontargeted metabolomics revealed that HP intervention would modulate metabolism by promoting levels of 3-hydroxybutyric acid, phosphatidylcholine (PC), and phosphatidylethanolamine (PE). These results demonstrated that HP had the ability to mitigate DSS-induced UC by suppressing oxidative stress and inflammation, maintaining the intestinal barrier, and modulating the intestinal flora. These findings will expand our knowledge of how HP functions and offer a theoretical foundation for using HP as a potential prebiotic to prevent UC. Full article

Neutrophil-myeloperoxidase (MPO) is a heme-containing peroxidase which produces excess amounts of hypochlorous acid during inflammation. While pharmacological MPO inhibition mitigates all indices of experimental colitis, no studies have corroborated the role of MPO using knockout (KO) models. Therefore, we investigated MPO deficient mice in a murine model of colitis. Wild type (Wt) and MPO-deficient mice were treated with dextran sodium sulphate (DSS) in a chronic model of experimental colitis with three acute cycles of DSS-induced colitis over 63 days, emulating IBD relapse and remission cycles. Mice were immunologically profiled at the gut muscoa and the faecal microbiome was assessed via 16S rRNA amplicon sequencing. Contrary to previous pharmacological antagonist studies targeting MPO, MPO-deficient mice showed no protection from experimental colitis during cyclical DSS-challenge. We are the first to report drastic faecal microbiota shifts in MPO-deficient mice, showing a significantly different microbiome profile on Day 1 of treatment, with a similar shift and distinction on Day 29 (half-way point), via qualitative and quantitative descriptions of phylogenetic distances. Herein, we provide the first evidence of substantial microbiome shifts in MPO-deficiency, which may influence disease progression. Our findings have significant implications for the utility of MPO-KO mice in investigating disease models. Full article

Transplantation of faecal microbiota (FMT) is generally considered a safe therapeutic procedure with few adverse effects. The main factors that limit the spread of the use of FMT therapy for idiopathic inflammatory bowel disease (IBD) are the necessity of minimising the risk of infection and transfer of another disease. Obtaining the animal model of UC (ulcerative colitis) by exposure to DSS (dextran sodium sulphate) depends on many factors that significantly affect the result. Per os intake of DSS with water is individual for each animal and results in the development of a range of various forms of induced UC. For this reason, the aim of our study was to evaluate the modulation and regenerative effects of FMT on the clinical and histopathological responses and the changes in the bowel microenvironment in pseudo germ-free (PGF) mice of the BALB/c line subjected to chemical induction of mild, moderate and serious forms of UC. The goal was to obtain new data related to the safety and effectiveness of FMT that can contribute to its improved and optimised use. The animals with mild and moderate forms of UC subjected to FMT treatment exhibited lower severity of the disease and markedly lower damage to the colon, including reduced clinical and histological disease index and decreased inflammatory response of colon mucosa. However, FMT treatment failed to achieve the expected therapeutic effect in animals with the serious form of UC activity. The results of our study indicated a potential safety risk involving development of bacteraemia and also translocation of non-pathogenic representatives of bowel microbiota associated with FMT treatment of animals with a diagnosed serious form of UC. Full article

Lactiplantibacillus plantarum D13 shows antistaphylococcal and antilisterial activity, probably due to the synthesis of a presumptive bacteriocin with antibiofilm capacity released in the cell-free supernatant (CFS), whose inhibitory effect is enhanced by cocultivation with susceptible strains. An in silico analysis of the genome of strain D13 confirmed the pln gene cluster. Genes associated with plantaricin biosynthesis, structure, transport, antimicrobial activity, and immunity of strain D13 were identified. Furthermore, the predicted homology-based 3D structures of the cyclic conformation of PlnE, PlnF, PlnJ, and PlnK revealed that PlnE and PlnK contain two helices, while PlnF and PlnJ contain one and two helices, respectively. The potential of the strain to modulate the intestinal microbiota in healthy or dextran sulphate sodium (DSS)-induced colitis mouse models was also investigated. Strain D13 decreased the disease activity index (DAI) and altered the gut microbiota of mice with DSS-induced colitis by increasing the ratio of beneficial microbial species (Allobaculum, Barnesiella) and decreasing those associated with inflammatory bowel disease (Candidatus Saccharimonas). This suggests that strain D13 helps to restore the gut microbiota after DSS-induced colitis, indicating its potential for further investigation as a probiotic strain for the prevention and treatment of colitis. Full article