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• Macrophages are key immune cells in inflammatory bowel disease. • Alcohol is a widely used solvent in pharmaceutical formulations. • Alcohol consumption is associated with an increased risk and severity of colitis. • Alcohol promotes macrophage M2b polarization through the TRPV1-MAPK/NF-κB pathways. Macrophages exhibit different phenotypes in inflammatory bowel disease (IBD) and promote inflammation or tissue repair depending on their polarization state. Alcohol is a widely used solvent in pharmaceutical formulations, and its consumption is associated with an increased risk of colitis; however, its effects on macrophages in IBD remain poorly understood. This study aimed to investigate the effect of alcohol on macrophages in dextran sodium sulfate (DSS)-induced colitis and understand the underlying mechanisms. DSS-treated C57BL/6 mice were exposed to varying concentrations of alcohol, transient receptor potential vanilloid 1 (TRPV1) antagonist, and 5-aminosalicylic acid. The distal colon was resected, fixed, stained, and histologically analyzed, through hematoxylin and eosin (H&E) staining and immunofluorescence staining. Ratio [Ca2+]i measurements, western blotting, quantitative polymerase chain reaction, cytokine measurements, and RNA sequencing analyses were also performed. Peritoneal macrophages and RAW264.7 cells were used for in vitro experiments, and various assays were performed to evaluate cellular responses, gene expression, and signaling pathways. Alcohol exacerbated DSS-treated mice colitis and promoted the secretion of various inflammatory cytokines from colonic macrophages. Alcohol enhances the calcium ion influx induced by lipopolysaccharide (LPS) in peritoneal macrophages, while the TRPV1 antagonist capsazepine (CPZ) inhibits LPS- and/or alcohol- induced calcium influx in macrophages. Alcohol and LPS activate the MAPK/P38, MAPK/ERK, and NF-κB signaling pathways and induce the macrophage M2b polarization, resulting in the increased expression level of inflammatory cytokines such as Tnf, Il1b, and Il10. Additionally, CPZ can inhibit the facilitatory effects of alcohol or LPS on the abovementioned pathways and inflammatory factors, reversing macrophage M2b polarization and promoting alcohol-induced colitis. The inhibition of nucleotide binding oligomerization domain containing 2 (NOD2) partially suppressed the alcohol and LPS effects on macrophages. Alcohol exacerbates experimental colitis and induces M2b polarization of macrophage via TRPV1-MAPK/NF-κB. Our study provides new insights into the potential therapeutic targets for IBD treatment by elucidating the role of TRPV1 in alcohol-exacerbated colitis, using CPZ as a potential therapeutic option. The identification of transient receptor potential ankyrin subtype 1 (TRPA1) as a therapeutic target expands the scope of future research. [Display omitted] [ABSTRACT FROM AUTHOR]

Latilactobacillus curvatus is a candidate probiotic that is known to have antioxidant, immunomodulatory, anti-obesity, and colitis-relieving beneficial effects. Here, we evaluated the effects of Lt. curvatus CCFM1268 on dextran sulfate sodium (DSS)-induced Caco-2 cell damage and colitis in mice. Our results demonstrate that Lt. curvatus CCFM1268 significantly restored cell viability and promoted the expression of barrier factors in vitro. In vivo , Lt. curvatus CCFM1268 significantly restored weight loss and colon damage in mice and modulated the levels of inflammatory factors and tight junction proteins in the colon. Latilactobacillus curvatus CCFM1268 also reduced the abundance of conditionally pathogenic bacteria including Escherichia_shigella and Alistipes , enriched the abundance of Lactobacillus , Parabacteroides , Enterococcus and Faecalibaculum , and significantly increased the concentrations of acetic, propionic, and butyric acid in the gut. These results indicate that Lt. curvatus CCFM1268 can alleviate colitis by inhibiting colonic inflammation, repairing the gut barrier, regulating the gut microbiota composition, and secreting metabolites, which was demonstrated both in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Background and Aims Tyrosine kinase 2 [TYK2] is required for the signalling of key cytokines in the pathogenesis of inflammatory bowel disease [IBD]. We assessed the efficacy of a novel selective TYK2 inhibitor [TYK2i] in experimental colitis, using pharmacological and genetic tools. Methods At onset of T cell transfer colitis, RAG1-/- mice received vehicle or TYK2i daily by oral gavage. T cells lacking TYK2 kinase activity [TYK2KE] were used to confirm selectivity of the inhibitor. To this end, RAG1-/- or RAG1-/-TYK2KE animals were transferred with either wild type [WT] or TYK2KE-CD45RBhigh colitogenic T cells. Loss of body weight, endoscopic disease, the disease activity index [DAI], and histopathology scores were recorded. Tissues were analysed ex vivo for lymphocyte populations by flow cytometry. The impact of TYK2 inhibition on human DC-T cell interactions were studied using autologous Revaxis specific T cell assays. Results TYK2i [70 mg/kg] prevented weight loss and limited endoscopic activity during T cell transfer colitis. TYK2i [70 mg/kg] decreased DAI. Whereas transfer of WT T cells into RAG-/-TYK2KE hosts induced colitis, TYK2KE T cells transferred into RAG1-/-TYK2KErecipients failed to do so. Ex vivo analysis showed a decrease in colon tissue Th1 cells and an increase in Th17 cells upon transfer of TYK2KE-CD45RBhigh cells. In human antigen-triggered T cells, TYK2i displayed reduced Th1 differentiation, similar to murine Th1 cells. Conclusions Oral administration of TYK2i, as well as transfer of T cells lacking TYK2 activity, reduced human Th1 differentiation and ameliorated the course of murine T cell transfer colitis. We conclude that TYK2 is a promising drug target for the treatment of IBD. [ABSTRACT FROM AUTHOR]

Background Tissue inflammation in inflammatory bowel diseases [IBD] is associated with local acidification. Genetic variants in the pH-sensing G protein-coupled receptor 65, also known as T cell death-associated gene 8 [TDAG8], have been implicated in IBD and other autoimmune diseases. Since the role of TDAG8 in intestinal inflammation remains unclear, we investigated the function of TDAG8 using murine colitis models. Methods The effects of TDAG8 deficiency were assessed in dextran sodium sulphate [DSS], IL-10-/-, and T cell transfer colitis murine models. RNA sequencing of acidosis-activated TDAG8-/- and wild-type [WT] peritoneal macrophages [MΦs] was performed. Results mRNA expression of IFN-γ, TNF, IL-6, and iNOS in TDAG8-/- mice increased significantly in colonic lymphoid patches and in colonic tissue in acute and chronic DSS colitis, respectively. In transfer colitis, there was a trend towards increased IFN-γ, iNOS, and IL-6 expression in mice receiving TDAG8-/- T cells. However, absence of TDAG8 did not lead to changes in clinical scores in the models tested. Increased numbers of infiltrating MΦs and neutrophils, but not CD3+ T cells, were observed in DSS-treated TDAG8-/- mice. No differences in infiltrating CD3+ T cells were observed between mice receiving TDAG8-/- or WT naïve T cells in transfer colitis. RNA sequencing showed that acidosis activation of TDAG8 in MΦs modulated the expression of immune response genes. Conclusions TDAG8 deficiency triggers colonic MΦ and neutrophil infiltration, and expression of pro-inflammatory mediators in DSS colitis models. In transfer colitis, mice receiving TDAG8-/- T cells presented a significantly higher spleen weight and a tendency towards increased expression of pro-inflammatory markers of monocyte/MΦ activity. [ABSTRACT FROM AUTHOR]

Abstract Background This study aimed to analyze the effects of quercitrin, which has anti-inflammatory properties, on bacterial translocation in inflammatory bowel diseases by using an experimental colitis model. Methods Forty male Wistar-Albino rats were used in the study. Rats were divided into 4 groups (control, colitis, treatment 1 and 2 groups). The rats in the control group were given normal drinking water. In the colitis group, colitis was induced by 5% DSS in drinking water. The control and colitis groups underwent operation on Day 7. In the 2 treatment groups, 5% DSS was added to drinking water for the first 7 days and the groups were treated with quercitrin at the doses of 1 and 5 mg/kg/day for the following 10 days. Treatment groups operated on Day 18. Blood samples were taken for blood culture and left colectomy was performed. The inflammation in the colon was macroscopically and microscopically evaluated and graded. Tissue samples were taken (liver, spleen and mesenteric lymph nodes (MLN)) for tissue culturing in order to assess bacterial translocation. Tissue myeloperoxidase (MPO), serum tumor necrosis factor-alpha (TNF-α) and plasma endotoxin levels were measured. Results When the control and colitis groups were compared, observed that colitis was induced by DSS (p < 0.05). When the colitis and treatment groups were compared, it was found that quercitrin had a significant therapeutic effect (p < 0.05). Conclusion In the experimental colitis model established by using DSS, treatment with quercitrin resulted in a histopathological improvement and reduction in biochemical parameters, inflammation and in bacterial translocation (p < 0.05). [ABSTRACT FROM AUTHOR]

Dietary supplementation with pure cis9, trans11 isomer of Conjugated Linoleic Acid –known as Rumenic Acid (RA)– improves cytoprotective defenses downstream through the activation of nuclear factor-E2-related factor-2(Nrf2). This capability, when Rumenic Acid is consumed in the form of foods, is still unknown. The ability of standard ( St ) or cow milk naturally-enriched in RA ( En ) to activate Nrf2 pathway and its impact on dextran sodium sulfate (DSS)-induced colitis was comparatively evaluated. Activity of Nrf2 pathway was investigated in colonic tissue of BALB/c mice, receiving 4-week supplement with skimmed milk ( SK ), St or St reinforced with pure RA ( RSt ) providing increasing RA dose (0, 124 or 404 mg RA/kg -1 b.w, respectively). Next, the anti-oxidant/ anti-inflammatory effect produced by St or En treatment (383 mg RA/kg -1 b.w.) was explored. Finally, macroscopic and histomorphologic features of colitis were evaluated in animals challenged with 5% (w/v) DSS, at the end of St or En treatment. Significant activation of Nrf2 pathway is associated with RSt and En intake (P<0.05), but not with SK or En treatment. En pre-treatment offers better protection, in comparison with St , against pro-oxidant, pro-inflammatory signs (P<0.01) and macroscopic signs triggered by DSS. It can be concluded that Nrf2 activation by higher RA amount contained in En is, at least in part, responsible for the improved protection associated with En intake against DSS-induced colitis. [ABSTRACT FROM AUTHOR]

This study investigates the effects of a pea ( Pisum sativum ) seed albumin extract (PSE) on the colonic microbiota in a model of experimental dextran sodium sulfate (DSS)-induced colitis in mice. Male C57BL/6J mice were assigned to three groups: one non-colitic and two colitic. Colitis was induced by incorporating DSS (3.5%) in the drinking water for four days, after which DSS was removed. The pre-treated group received orally PSE (15 g/kg·day) starting two weeks before colitis induction, and was maintained for nine days after. Mice pre-treated with PSE showed a recovery in colon length compared with non-treated DSS group. Both RT-qPCR and pyrosequencing analysis showed that DSS induced significant modifications in the microbiota composition of colonic contents and tissue. In conclusion, PSE modulated colonic microbiota in a model of experimental dextran sodium sulfate (DSS)-induced colitis in mice, and prevented colonic DSS induced dysbiosis in mice. [ABSTRACT FROM AUTHOR]

Summary Background & aims Nutritional therapy is a viable therapeutic option for the treatment of Crohn disease (CD). Therefore improving nutritional therapy would greatly benefit CD patients. The aim of this study was to define the anti-inflammatory properties of a novel nutritional polymeric formula (PF) in comparison to a currently available standard PF. Methods Dextran sodium sulfate (DSS) was utilized to induce colitis in C57BL/6 mice with mice randomized to receive either standard PF or novel PF in addition to control groups. Changes in body weight were recorded and colonic damage was assessed histologically and biochemically. Additional experiments were also included where the cytokine response of colonic biopsies from pediatric CD patients was measured following exposure to standard PF or novel PF. Results DSS induced significant body weight loss, morphological changes in the colon, increased myeloperoxidase (MPO) activity and up-regulated colonic mRNA expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12 and monocyte chemoattractant protein (MCP)-1, as well as associated histological changes. Other than histological damage, these inflammatory changes were reversed by both novel and standard PF. However, the novel PF, but not standard PF, completely suppressed TNF-α, IL-6 and IL-8 levels from cultured biopsies. Conclusions Newly developed nutritional formula reproducibly ameliorated DSS-induced colitis in a murine model, although this response was not measurably different to standard PF. However, the novel PF was significantly superior in suppressing inflammatory cytokine release from cultured colonic biopsies. Collectively, these findings support a possible role for novel PF in advancing nutritional therapy for CD patients. [ABSTRACT FROM AUTHOR]

Summary Background & aims IBD is a chronic disorder of the gastrointestinal tract characterized by mucosal inflammation and epithelial damage. Biologic therapy has significantly improved the course of the disease but there are still a high percentage of patients that do not respond to current therapies. We aim to determine the effects of the flesh ethanolic extract of Hylocereus polyrhizus (EH) in a mice model of colitis induced by TNBS. Methods Balb/c mice received TNBS (175 mg/kg, 100 μl, i.r.) and six and thirty hours later were administered with EH (1 g/kg, i.p.). Mice were weighted daily and after sacrificing (2 and 4 days after TNBS) we analyzed mucosal histology, myeloperoxidase activity (MPO), the expression of pro-inflammatory molecules (qPCR) and NF-κB and Iκβ-α protein levels. The chemical characterization of the EH was determined by LC–MS/MS. Results The administration of EH to TNBS-treated mice prevented (P < 0.05) the loss of body weight and significantly reduced in the colon: a) histological damage score, b) MPO enzymatic activity c) the expression of pro-inflammatory molecules and d) Iκβ-α degradation and nuclear NF-κβ protein levels. The LC–MS analysis detected metabolites such as polyphenols and fatty acids. Conclusion Systemic administration of the ethanolic extract of H. polyrhizus exerts an anti-inflammatory effect and prevents murine colitis induced by TNBS. [ABSTRACT FROM AUTHOR]

Background and Aims: In recent years, mesenchymal stromal cells [MSCs] emerged as a promising therapeutic option for various diseases, due to their immunomodulatory properties. We previously observed that intraperitoneally injected MSCs in experimental colitis form spherical shaped aggregates. Therefore, we aggregated MSCs in vitro into spheroids and injected them intraluminally in mice with established colitis, to investigate whether these MSC spheroids could alleviate the colitis. Methods: We injected 0.5 x 106 MSCs in spheroids, 2.0 x 106 MSCs in spheroids, or phosphatebuffered saline [PBS] as a treatment control, via an enema in mice with established dextran sulphate sodium [DSS]-induced colitis. Body weight was measured daily and disease activity score was determined at sacrifice. Endoscopy was performed to evaluate mucosal healing. After sacrifice, both systemic and local inflammatory responses were evaluated. Results: Intraluminally injected MSC spheroids alleviated DSS-induced colitis, resulting in significantly less body weight loss and lower disease activity score at sacrifice when a high dose of MSC spheroids was administered. However, the percentage of mucosal lesions in the distal colon and endoscopy scores were not significantly lower after treatment with 2.0 x 106 MSCs in spheroids compared with PBS-treated mice. Systemic inflammation marker serum amyloid A [SAA] was significantly reduced after treatment with 2.0 x 106 MSCs in spheroids. In addition, local cytokine levels of IFN-ɣ, TNF-α, IL-6, and IL-17a, as well as numbers of macrophages and neutrophils, showed a clear decrease--though not always significant--after intraluminal injection of the MSC spheroids. Conclusion: Intraluminally injected MSC spheroids at least partially attenuate experimental colitis, with fewer phagocytes and proinflammmatory cytokines, when a high dose of MSCs in spheroids was administered. Conclusion: Intraluminally injected MSC spheroids at least partially attenuate experimental colitis, with fewer phagocytes and proinflammmatory cytokines, when a high dose of MSCs in spheroids was administered. [ABSTRACT FROM AUTHOR]

Background and Aims: Proper interpretation of data from preclinical animal studies requires thorough knowledge of the pathophysiology of both the human disease and animal models. In this study, the expression of inflammatory bowel disease [IBD]-associated genes was characterised in mouse models of colitis to examine the underlying molecular pathways and assess the similarity between the experimental models and human disease. Methods: RNA sequencing was performed on colon biopsies from Crohn's disease [CD] patients, ulcerative colitis [UC] patients and non-IBD controls. Genes shown to be significantly dysregulated in human IBD were used to study gene expression in colons from a piroxicam-accelerated colitis interleukin-10 knockout [PAC IL-10 k.o.], an adoptive transfer [AdTr] and a dextran sulfate sodium [DSS] colitis mouse model. Results: Of 115 literature-defined genes linked to IBD, 92 were significantly differentially expressed in inflamed mucosa of CD and/or UC patients compared with non-IBD controls. The most upregulated genes were shared by both diseases, including REG1A, LCN2, NOS2, CXCL1-2, and S100A9. Of those 92 IBD-associated genes, 71 [77%] were significantly dysregulated in PAC IL-10 k.o. mice, whereas 59 [64%] were significantly dysregulated in AdTr mice compared with wild-type controls. Some of the most upregulated genes, including S100a8-9, Nos2, and Lcn2, were shared by the colitis models and correlated with disease activity. Conclusions: IBD and experimental murine colitis have a high degree of similarity in the colonic transcriptional profile, probably secondary to non-specific inflammatory processes. However, differences do exist between models, emphasising the need for careful selection and interpretation of qualified animal models in preclinical research. [ABSTRACT FROM AUTHOR]

Background and aims Pharmacological treatment and/or maintenance of remission in inflammatory bowel diseases (IBD) is currently one of the biggest challenge in the field of gastroenterology. Available therapies are mostly limited to overcoming the symptoms, but not the cause of the disease. Recently, the endocannabinoid system has been proposed as a novel target in the treatment of IBD. Here we aimed to assess the anti-inflammatory action of the novel fatty acid amide hydrolase (FAAH) inhibitor PF-3845 and its effect on the endocannabinoid and related lipid metabolism during the course of experimental colitis. Methods We used two models of experimental colitis in mice (TNBS- and DSS-induced) and additionally, we employed LC/MS/MS spectrometry to determine the changes in biolipid levels in the mouse colon during inflammation. Results We showed that the FAAH inhibitor PF-3845 reduced experimental TNBS-induced colitis in mice and its anti-inflammatory action is associated with altering the levels of selected biolipids (arachidonic and oleic acid derivatives, prostaglandins and biolipids containing glycine in the mouse colon). Conclusions We show that FAAH is a promising pharmacological target and the FAAH-dependent biolipids play a major role in colitis. Our results highlight and promote therapeutic strategy based on targeting FAAH-dependent metabolic pathways in order to alleviate intestinal inflammation. [ABSTRACT FROM AUTHOR]

Abstract: Background: In inflammatory bowel disease (IBD), gut inflammation is associated with the activation of nuclear factor kappa B (NF-κB), a key pro-inflammatory transcription factor. Aim: To investigate the therapeutic potential of a novel, specific NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), we examined its effect on IBD using murine experimental colitis models. Methods: The in vitro effect of DHMEQ was evaluated by inflammatory cytokine production and p65 immunostaining using HT-29 and RAW264.7 cells. The in vivo therapeutic effect of DHMEQ was studied in colitis induced by dextran sulphate sodium (DSS) and trinitrobenzenesulphonic acid (TNBS). In these, progression and severity of colitis was mainly assessed by the disease activity index (DAI), histopathology, cellular infiltration, and mRNA expression levels of pro-inflammatory cytokines in the colonic tissues. Results: In RAW264.7 cells, DHMEQ significantly inhibited tumour necrosis factor (TNF)-α and interleukin (IL)-6 production induced by LPS in a dose-dependent manner by blocking the nuclear translocation of NF-κB. In addition, DHMEQ inhibited IL-8 production induced by LPS in HT-29 cells. DHMEQ significantly ameliorated DSS colitis as assessed by DAI scores, colonic oedema, and histological scores. Immunohistochemistry revealed that DHMEQ inhibited colonic infiltration of nuclear p65+ cells, CD4+ lymphocytes, and F4/80+ macrophages. mRNA expression levels of the pro-inflammatory cytokines, such as IL-1β, TNF-α, IL-6, IL-12p40, IL-17, and MCP-1 were also suppressed by DHMEQ administration. Furthermore, DHMEQ significantly ameliorated TNBS colitis as assessed by body-weight changes and histological scores. Conclusion: DHMEQ ameliorated experimental colitis in mice. These results indicate that DHMEQ appears to be an attractive therapeutic agent for IBD. [Copyright &y& Elsevier]

Abstract: Background and Aims: Transglutaminases are tissue enzymes involved in different neuronal processes including maintenance and signalling. However, their up-regulation elicited by a variety of noxae contributes to neurodegeneration. This study tested the hypothesis that experimental inflammation evoked transglutaminase up-regulation in myenteric neurons and that this event had an impact on neuronal survival. Methods: Rats with or without trinitro-benzene-sulphonic acid-induced colitis were used. One week after colitis induction, longitudinal muscle-myenteric plexus preparations were obtained from left colon to assess tissue-transglutaminase activity, protein and mRNA expression. Double labelling immunofluorescence using antibodies to neuron-specific enolase and transglutaminase was performed to identify myenteric neurons expressing transglutaminase. Additional sets of experiments evaluated the involvement of transglutaminase in the apoptotic process of cultured myenteric neurons. Results: Compared to controls, rats with colitis showed several tranglutaminase/neuron-specific enolase positive myenteric neurons. Western blot analysis and RT-PCR confirmed that in rats with colitis, the increased neuronal transglutaminase-immunoreactivity was associated with an increased enzyme expression. Similarly, transglutaminase activity was significantly higher than in controls (1100±280mU/g vs. 725±119mU/g, p <0.05). In cultured myenteric neurons incubation with the specific transglutaminase inducer, retinoic acid, significantly increased neuronal apoptosis, whereas the presence of cystamine significantly reduced the number of apoptotic neurons. Conclusions: Experimental colitis evoked transglutaminase up-regulation and increased activity in myenteric neurons. This mechanism enhances neuronal susceptibility to apoptosis and could contribute to neuropathic changes during gut inflammation. [Copyright &y& Elsevier]

The pathogenesis of inflammatory bowel disease is thought to be a multifactorial process. One of the leading hypotheses is that an imbalance in normal gut flora induces an excessive immune response and contributes to inflammation in the gastrointestinal tract. Administration of probiotic bacteria reduces symptoms in patients suffering from inflammatory bowel diseases, probably via both manipulation of the microflora and stimulation of the intestinal immune system. In the current study the therapeutic potential of two different probiotics– Lactobacillus GG and a mixture of Streptococcus thermophilus, Lactobacillus acidophilus, and Bifidobacterium longum (YO-MIX™ Y 109 FRO 1000)—in a rat model of colitis were evaluated. Male Wistar rats were administered probiotics for three days simultaneously with colitis induction. Colonic damage was evaluated histologically and biochemically and colonic tissues, as well as fecal samples, were used for bacterial studies using 16S rRNA gene primers. Probiotics administration reduced the relative amounts of the pathogenic bacteria Aeromonas and Escherichia coli in the colonic tissue. However, whereas both probiotics affected colon morphology, only Lactobacillus GG administration reduced myeloperoxidase activity. We report the therapeutic rather than preventive potential of two different probiotics in an animal model of colitis. [ABSTRACT FROM AUTHOR]

Abstract: Background: Note that butyrate is utilised by colonocytes in energy production and that deficiency of this substance is observed in the colon of patients with chronic inflammatory bowel disease. Aims: We first assessed the efficacy of butyrate in rats with induced colitis, and since this condition represents a condition of increased risk of colonic neoplasia, we also evaluated whether butyrate treatment reduces susceptibility of the mucosa to the emergence of carcinoma in the colon of rats with experimental colitis. Materials and methods: Colitis was induced with trinitrobenzene-sulphonic acid and colonic tumours were induced with azoxymethane. Results: Colitis improved noticeably following treatment with butyrate and tumours emerging in colitis were significantly reduced in both size and number. Conclusions: The results obtained suggest the need for further study of the metabolic fate of butyrate and its role in maintaining the mucosal integrity of the colon. [Copyright &y& Elsevier]

Summary: Background & aims: Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. In inflammatory bowel disease (IBD), where major modifications of the intestinal microflora have been reported, there is an increasing interest in modulating the flora with probiotic products. This work addresses the anti-inflammatory potential of Lactibiane Tolérance, a probiotic dietary supplement (mixture of four strains) using in vitro and in vivo approaches. Methods: Comparison of the four individual strains and the commercial product reconstituted from them was conducted by in vitro tests (cytokine release after 24h stimulation of human peripheral blood mononuclear cells (PBMC)). The potential immunomodulatory characteristics of Lactibiane Tolérance were determined in vivo in an acute mice model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Assessment of colitis included blinded histological and macroscopic scores. Results: We showed that Lactibiane Tolérance has anti-inflammatory properties in vitro by stimulating IL-10 production and in vivo by conferring a significant protective effect in the TNBS-induced colitis model (more than 50% decrease of colitis symptoms, P<0.01). Conclusions: These results demonstrate that a probiotic dietary supplement, Lactibiane Tolérance, can significantly prevent the initial injury of TNBS and could stimulate the initiation of clinical trials in IBD. [Copyright &y& Elsevier]

PURPOSE: Inflammatory bowel disease is suggested to result from a dysregulated immune response toward intestinal microflora, which may be restored by probiotic therapy based on the concept of healthy microflora. Ideal probiotic bacteria may be beneficial in inflammatory bowel disease; however, the mechanism of action and the clinical efficacy of probiotic usage are still unclear. In the present study, the effect of exopolysaccharide producing probiotics was evaluated on an experimental colitis model in rats. METHODS: Colitis was induced by intracolonic administration of acetic acid. Then, rats were treated daily with two probiotic strains, Lactobacillus delbrueckii subsp. bulgaricus B3 strain (exopolysaccharide of 211 mg/l: high-EPS group) or Lactobacillus delbrueckii subsp. bulgaricus A13 strain (EPS of 27 mg/l: low-EPS group), which were given into the stomach. The non-colitis-fed control group was only treated with high-exopolysaccharide strain. The model-control and control groups were treated only with tap water. Rats were killed after a seven-day treatment period. Disease activity was quantified by use of histologic scores and colonic myeloperoxidase activity, which is a marker of neutrophil infiltration during inflammation. RESULTS: The enhanced inflammatory response was accompanied by a higher level of myeloperoxidase activity in the colitis group. Histologic scores of colonic damage and myeloperoxidase activity were lower in both probiotic-treated groups compared with those of the colitis control group (P < 0.001), although the mentioned scores improved significantly more in the high-EPS group than in the low-EPS group (P < 0.001). CONCLUSIONS: Exopolysaccharide-producing probiotics significantly attenuate experimental colitis, which may be mediated by exopolysaccharide in a dose-dependent manner. Therefore, exopolysaccharide-producing probiotics may be a promising therapeutic role in inflammatory bowel disease. [ABSTRACT FROM AUTHOR]