Sulfate Sodium-induced Colitis In Mice Research Articles

Diallyl trisulfide alleviates dextran sulphate sodium-induced colitis in mice by inhibiting NLRP3 inflammasome activation via ROS/Trx-1 pathway.

Diallyl trisulfide (DATS), a sulphur-containing compound isolated from the medicinal food plant garlic, has been previously reported to attenuate experimental colitis induced by either dextran sodium sulphate (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS) in mice; however, the underlying mechanism remains to be identified. In this study, we deciphered the key mechanism by which DATS alleviates ulcerative colitis (UC). We showed that oral administration of DATS for 10 consecutive days greatly restrained the infiltration of macrophages and the pathological changes in colonic tissues of mice with DSS-induced colitis. DATS treatment notably dampened the content of IL-1β and IL-18 and suppressed NLRP3 inflammasome activation in colon. Mechanistically, DATS effectively diminished the generation of ROS in macrophages. The suppressive effect of DATS on the activation of NLRP3 inflammasome and downregulation of IL-18 and IL-1β levels was blunted by xanthine oxidase. Further studies revealed that DATS inhibited NF-κB pathway activation by suppressing the expression of Trx-1, thereby inhibiting NLRP3 inflammasome activation. Trx-1 overexpression and interference in macrophages promoted and diminished NLRP3 inflammasome activation, respectively. In summary, garlic and its main active ingredient DATS have potentials to prevent and treat UC, and DATS functions by inhibiting NLRP3 inflammasome activation via Trx-1/ROS pathway.

Osa-miR168a, a Plant miRNA That Survives the Process of In Vivo Food Digestion, Attenuates Dextran Sulfate Sodium-Induced Colitis in Mice by Oral Administration.

Previous studies showed that osa-miR168a, a plant miRNA rich in fruits and vegetables, had cross-kingdom biological effects on immunocytes, silkworms, and rodents. In this study, the effects of miR168a on mouse colitis induced by dextran sulfate sodium (DSS) were investigated. The results showed that miR168a oligomers were resistant during the process of food digestion, ending up with a residual concentration of 67.8 ± 11.2 fM in mouse intestines 4 h after oral gavage. More importantly, direct oral administration of the miRNA to the colitis mice significantly ameliorated the progression of the disease, as evidenced by the reduction in DAI score, histopathological lesions, and proinflammatory cytokines. Repairing intestinal barrier function by promoting the regeneration of TJ proteins and the mucus layer, suppressing oxidative stress and colonic inflammation via modulating Nrf2 and NF-κB signaling pathways, and restoring the imbalanced gut microbiota caused by DSS are proposed mechanisms behind the anticolitis activity of miR168a. This study provided new evidence of the cross-kingdom regulatory effects of dietary miRNAs, suggesting the potential of the plant miRNA for the prevention and treatment of inflammatory bowel diseases.

ChiA: a major player in the virulence of Crohn’s disease-associated adherent and invasive Escherichia coli (AIEC)

ABSTRACT We investigated the role of ChiA and its associated polymorphisms in the interaction between Crohn’s disease (CD)-associated adherent-invasive Escherichia coli (AIEC) and intestinal mucosa. We observed a higher abundance of chiA among the metagenome of CD patients compared to healthy subjects. In dextran sulfate sodium-induced colitis mice model, AIEC-LF82∆chiA colonization was reduced in ileal, colonic and fecal samples compared to wild-type LF82. The binding of ChiA to recombinant human CHI3L1 or mucus was higher with the pathogenic polymorphism. The strength of ChiA-mucin interaction was 300-fold stronger than ChiA-rhCHI3L1. ChiA was able to degrade mucin to promote its growth and enabled LF82 to get closer to epithelial cells. The pathogenic polymorphism of ChiA had a stronger impact on mucus degradation than on the binding capability of AIEC to adhere to the intestinal epithelium. We observed that ChiA could favor an efficient bacterial invasion of intestinal crypts, and that ChiA, especially its pathogenic polymorphism, gives LF82 an advantage to uptake within Peyer’s patches, macrophages and mesenteric lymph nodes. All together, these data support the role of ChiA in the virulence of AIEC and show that it could be a promising target to reduce AIEC colonization in patients with CD.

Optimization of a gelatin/carboxymethylcellulose-based probiotic microcapsule and its application in preventing dextran sodium sulfate-induced colitis in mice.

Oral administration of probiotics has demonstrated substantial potential in alleviating colitis. However, most of the ingested microorganisms struggle to survive the harsh conditions of the gastrointestinal tract, leading to decreased efficacy. In the present study, using double emulsification (W1/O/W2) and complex coacervation methods, we developed a gelatin/carboxymethyl cellulose (CMC)-based probiotic microcapsule and analyzed the efficacy of encapsulated probiotics in preventing dextran sodium sulfate (DSS)-induced colitis in mice. Our results reveal that nearly 90% of the encapsulated probiotics remained viable after 30-day storage at 4°C and approximately 38.1% of viable bacteria (4.0 × 108 cfu/g) survived after 4-h simulated gastrointestinal digestion. In a DSS-induced colitis model, pretreatment with probiotics exerted significant protective effects, with the bacterial microcapsule-treated group having superior outcomes to those of the bacterial suspension plus empty carrier group. Probiotic treatments, especially those administered in the encapsulated form, significantly increased fecal short-chain fatty acid contents, and altered the intestinal microbial composition. The family Muribaculaceae, dominant bacteria in the mouse gut, may be the key microorganism involved in the BM regulation process. Our study presents an alternative approach to treating colitis using probiotics. PRACTICAL APPLICATION: The encapsuled probiotic showed remarkable storage stability at 4°C, maintained good vitality after simulated digestion, and gained superior outcomes in preventing colitis. Our results offer an alternative approach for the probiotic preparations aiming to prevent the intestinal inflammation.

Attenuation by Zhiqiao neohesperidin on dextran sulfate sodium-induced colitis in mice through inhibition of the TLR4/NF-κB pathway

Attenuation by Zhiqiao neohesperidin on dextran sulfate sodium-induced colitis in mice through inhibition of the TLR4/NF-κB pathway

Phage cocktail inhibits inflammation and protects the integrity of the intestinal barrier in dextran sulfate sodium-induced colitis mice model

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by abdominal pain, diarrhea, and rectal bleeding. This study aims to explore the protective effects of a phage cocktail (108 PFU/mL of Clostridium perfringens phage, 108 PFU/mL of Escherichia coli phage, and 108 PFU/mL of Salmonella phage) on a mouse colitis model induced by dextran sulfate sodium (DSS) and its potential toxic effects on normal mice. The results demonstrate that the phage cocktail significantly alleviates clinical symptoms in mice, reduces colon shortening, weight loss, and colonic pathological damage. Furthermore, the phage cocktail markedly suppresses the inflammatory response and safeguards intestinal barrier integrity in the colonic tissues of the mouse colitis model. Preliminary investigation of the toxic effects of the phage cocktail in mice indicates that continuous administration for 14 days does not yield statistically significant differences in hematological and blood biochemical parameters, and specific pathological changes are absent in histopathological examination results. The aforementioned findings suggest that the phage cocktail exhibits anti-inflammatory and intestinal barrier protective effects in the mouse colitis model, and it does not exert significant toxic side effects on mice.

Sheep (Ovis aries) Milk Exosomal miRNAs Attenuate Dextran Sulfate Sodium-Induced Colitis in Mice via TLR4 and TRAF-1 Inhibition.

Mammalian milk exosomal miRNAs play an important role in maintaining intestinal immune homeostasis and protecting epithelial barrier function, but the specific miRNAs and whether miRNA-mediated mechanisms are responsible for these benefits remain a matter of investigation. This study isolated sheep milk-derived exosomes (sheep MDEs), identifying the enriched miRNAs in sheep MDEs, oar-miR-148a, and oar-let-7b as key components targeting TLR4 and TRAF1, which was validated by a dual-luciferase reporter assay. In dextran sulfate sodium-induced colitis mice, administration of sheep MDEs alleviated colitis symptoms, reduced colonic inflammation, and systemic oxidative stress, as well as significantly increased colonic oar-miR-148a and oar-let-7b while reducing toll-like receptor 4 (TLR4) and TNF-receptor-associated factor 1 (TRAF1) level. Further characterization in TNF-α-challenged Caco-2 cells showed that overexpression of these miRNAs suppressed the TLR4/TRAF1-IκBα-p65 pathway and reduced IL-6 and IL-12 production. These findings indicate that sheep MDEs exert gastrointestinal anti-inflammatory effects through the miRNA-mediated modulation of TLR4 and TRAF1, highlighting their potential in managing colitis.

Proanthocyanidins and β-Glucan Synergistically Regulate Intestinal Inflammation in Dextran Sulfate Sodium-Induced Colitis Mice.

Proanthocyanidins (PA) have been proven to have an anti-inflammation effect in multiple models by regulating oxidative stress. β-glucan (BG) could alleviate colitis from the perspectives of intestinal permeability and gut microbiota. In the present study, the synergistic anti-inflammatory function of PA and BG was explored from multiple aspects including immune response, intestinal barrier, gut microbiota, and differential metabolites. The results showed that the supplementation of PA and BG improved the colitis symptoms including atrophy of the colon, body weight loss, and organ index increase. Additionally, inflammatory cytokine levels and oxidative stress status were significantly regulated with the intake of PA and BG. Moreover, PA and BG intervention improved intestinal permeability and promoted the expression of barrier proteins. The microbiome and metabolic profile of cecal contents showed that PA and BG supplementation increased the abundance of anti-inflammatory bacteria and decreased the abundance of pro-inflammatory bacteria. Furthermore, some beneficial metabolites involved in amino acid metabolism, carbohydrate metabolism, and biosynthesis of other secondary metabolite pathways were increased. Overall, these findings have demonstrated the regulation of the inflammatory response and remodel of metabolite profiles by PA and BG complexes, indicating that it may serve as a new strategy for inflammatory bowel disease treatment in the future.

Amelioration of dextran sodium sulphate-induced colitis in mice by treatment with Lactobacillus rhamnosus and Lactobacillus reuteri: intraspecific and interspecific patterns

Lactobacillus rhamnosus (Rh) and Lactobacillus reuteri (Re) are well-known probiotic species in inflammatory bowel disease (IBD) research. The variations between these species’ efficacy against colitis, and their model of action in this regard, are intriguing and enable treatment to be individually tailored to patients. In this study, four strains each of Rh and Re were isolated from fecal samples and their draft genomes were sequenced. The anti-colitis activities of both strains involved various aspects of intestinal immune, physical, chemical, and biological barrier function. Strikingly, the tested strains exhibited considerable interspecies and intraspecies specificity in colitis amelioration. Rh strains significantly outperformed Re strains in terms of short-chain fatty acid synthesis. Nevertheless, Re strains were more effective than Rh strains in inhibiting production of inflammatory factors; promoting production of intestinal mucus, antimicrobial peptides, and tight junction proteins; and supporting the stem cell compartment. This accounts for the anti-colitis outcomes of Re strains being superior to those of Rh strains. In addition, the effective Rh and Re strains were found to express high concentrations of specific carbohydrate metabolism- and prophage-related genes, respectively. Taken together, the results of this study could assist researchers in developing effective therapies for IBD.

Multiomics analysis reveals the potential mechanism of high-fat diet in dextran sulfate sodium-induced colitis mice model.

A high-fat diet (HFD) is recognized as an important contributor to inflammatory bowel disease (IBD). However, the precise underlying mechanism of HFD on IBD remains elusive. This study aimed to investigate the potential mechanism by which HFD affects IBD using 16S rRNA-sequencing and RNA-seq technology. Results indicated that HFD-treated mice exhibited notable alternations in the structure and composition of the gut microbiota, with some of these alternations being associated with the pathogenesis of IBD. Analysis of the colon transcriptome revealed 11 hub genes and 7 hub pathways among control, DSS-induced colitis, and HFD + DSS-treated groups. Further analysis explores the relationship between the hub pathways and genes, as well as the hub genes and gut microbiota. Overall, the findings indicate that the impact of HFD on DSS-induced colitis may be linked to intestinal dysbiosis and specific genes such as Abca8b, Ace2, Apoa1, Apoa4, Apoc3, Aspa, Dpp4, Maob, Slc34a2, Slc7a9, and Trpm6. These results provide valuable insights for determining potential therapeutic targets for addressing HFD-induced IBD.

Protective effect of walnut active peptide against dextran sulfate sodium-induced colitis in mice based on untargeted metabolomics

Inflammatory bowel disease (IBD) is a chronic condition characterized by inflammation of the digestive tract, whose exact cause remains unknown, and its prevalence is on the rise. This study investigated the effects of a walnut-derived peptide LPLLR (LP-5) on intestinal inflammation and metabolism in IBD mice. Metabolomics revealed that LP-5 regulated the levels of metabolites, such as thalsimidine, fumagillin, and geniposide, and LP-5 could regulate several signaling pathways, such as protein digestion and absorption, aminoacyl-tRNA biosynthesis, and ABC transporters. Additionally, LP-5 alleviated dextran sulfate sodium (DSS)-induced colitis by modulating autophagy and inflammasome pathways. Western blotting demonstrated that LP-5 reduced the expressions of NLRP3, Caspase-1, ASC and IL-1β, and increased the expressions of Beclin-1 and LC3-II/LC3-I, corresponding to activation of the AMPK/mTOR/ULK1 pathway. These findings suggested that LP-5 activated autophagy in vivo to suppress inflammation and modulate metabolic substances, highlighting potential implications for gut health and the development of functional foods containing LP-5.

A comparative analysis of the composition of the primary bioactive molecules, antioxidant activities, and anti-inflammation abilities of the roots of Zanthoxylum nitidum harvested at different years of cultivation

Zanthoxylum nitidum is a traditional medicinal herb prevalent in China and Southeast Asia. However, despite being a widely cultivated perennial woody plant, an accurate reference and guide for determining the appropriate harvesting age in lacking. This study employed high-performance liquid chromatography (HPLC) and ultraviolet-visible (UV-Vis) spectrophotometry, along with in vitro antioxidant and in vivo anti-inflammatory assays, to comprehensively analyze and compare the roots of Z. nitidum at 1–9 and 14 years. The results indicated a positive correlation between the increase in age and the root biomass. The highest decoction rates were observed in the roots of the 5- (44.08 %) and 4-year-old plants (40.42 %). However, the total alkaloid content (TAC) and the levels of nitidine chloride (NC), chelerythrine, and sanguinarine chloride initially increased but then decreased; their highest contents were 1.49 % (3-year-old), 0.50 % (7-year-old), 0.50 % (5-year-old), and 0.061 % (6-year-old), respectively. The levels of magnoflorine exhibited a trend of 3-year peaks; the respective contents were 0.36 % (3-year-old), 0.30 % (5-year-old), and 0.33 % (14-year-old). The change in the in vitro antioxidant potency composite index correlated with the wave-like trends in the total flavonoid content (TFC) and total phenolic acid (TPA). The indices for 9-, 5-, and 3-year-olds ranked among the top three and were >90. Extracts of Z. nitidum roots demonstrated a therapeutic effect in dextran sulfate sodium-induced ulcerative colitis mice, with that from the roots of 5-year-old plants showing the highest impact. Overall, the Z. nitidum roots of 4–6-year-old plants can be harvested as high-quality raw materials that meet the Pharmacopoeia of the People's Republic of China standards. This study provides scientific references for aspects such as the rational harvesting of Z. nitidum during artificial cultivation, the optimal utilization of land resources, and clinical use.

Xiaoyankangjun tablet alleviates dextran sulfate sodium-induced colitis in mice by regulating gut microbiota and JAK2/STAT3 pathway

Xiaoyankangjun tablet (XYKJP) is a traditional Chinese medicine formulation used to treat intestinal disorders in clinical practice. However, the specific therapeutic mechanism of action of XYKJP in colitis has not yet been elucidated. This study aimed to reveal the multifaceted mechanisms of action of XYKJP in treating colitis. The model established based on DSS-induced colitis in C57BL/6 mice was employed to estimate the effect of XYKJP on colitis, which was then followed by histological assessment, 16S rRNA sequencing, RT-qPCR, ELISA, and Western blot. XYKJP alleviated the symptoms of DSS-induced colitis mainly by reducing oxidative stress, inflammatory responses, and intestinal mucosal repair in colitis tissues. In addition, XYKJP regulated the intestinal flora by increasing the relative abundance of Akkermansia and Bifidobacterium and reducing the relative abundance of Coriobacteriaceae_UCG-002. Mechanistically, XYKJP increased the content of short-chain fatty acids (SCFAs) in the feces, particularly propanoic acid and butyric acid, activated their specific receptor GPR43/41, furthermore activated the Nrf2/HO-1 pathway, and suppressed the JAK2/STAT3 pathway. XYKJP significantly alleviated the symptoms of experimental colitis and functioned synergistically by regulating the intestinal flora, increasing the production of SCFAs, and activating their specific receptors, thereby repressing oxidative stress and inflammation.Graphical

Genistein alleviates dextran sulfate sodium-induced colitis in mice through modulation of intestinal microbiota and macrophage polarization.

Ulcerative colitis (UC) is a colonic immune system disorder, manifested with long duration and easy relapse. Genistein has been reported to possess various biological activities. However, it remains unclear whether genistein can ameliorate UC by modulating the homeostasis of the intestinal bacterial community. The dextran sodium sulfate (DSS)-induced UC mice were administrated with genistein (20mg/kg/day) or genistein (40mg/kg/day) for ten days. The general physical condition of the mice was monitored. After sacrifice, the changes in colon length and colonic pathological morphology were observed. The expression of intestinal barrier proteins, inflammatory cytokines, and macrophage markers in the colon was detected. The composition and metabolic products of the intestinal microbiota were analyzed. Genistein treatment visibly improved body weight change and disease activity index in DSS-induced mice. Genistein treatment ameliorated colonic pathological alterations and promoted the expression of mucin-2 and tight junction proteins. Genistein administration inhibited myeloperoxidase activity and colonic inflammatory cytokines. Furthermore, genistein administration improved the structure of the intestinal microbial community, promoted the production of short-chain fatty acids, and modulated macrophage polarization. These results revealed that genistein mediated macrophage polarization balance by improving intestinal microbiota and its metabolites, thereby alleviating DSS-induced colitis.

Weissella paramesenteroides NRIC1542 inhibits dextran sodium sulfate-induced colitis in mice through regulating gut microbiota and SIRT1/NF-κB signaling pathway.

Inflammatory bowel disease (IBD) is a kind of recurrent inflammatory disorder of the intestinal tract. The purpose of this study was to investigate the effects of Weissella paramesenteroides NRIC1542 on colitis in mice. A colitis model was induced by adding 1.5% DSS to sterile distilled water for seven consecutive days. During this process, mice were administered different concentrations of W. paramesenteroides NRIC1542. Colitis was assessed by DAI, colon length and hematoxylin-eosin staining of colon sections. The expressions of NF-κB signaling proteins and the tight junction proteins ZO-1 and occludin were detected by western blotting, and the gut microbiota was analyzed by 16S rDNA. The results showed that W. paramesenteroides NRIC1542 significantly reduced the degree of pathological tissue damage and the levels of TNF-α and IL-1β in colonic tissue, inhibiting the NF-κB signaling pathway and increasing the expression of SIRT1, ZO-1 and occludin. In addition, W. paramesenteroides NRIC1542 can modulate the structure of the gut microbiota, characterized by increased relative abundance of Muribaculaceae_unclassified, Paraprevotella, Prevotellaceae_UCG_001 and Roseburia, and decrease the relative abundance of Akkermansia and Alloprevotella induced by DSS. The above results suggested that W. paramesenteroides NRIC1542 can protect against DSS-induced colitis in mice through anti-inflammatory, intestinal barrier maintenance and flora modulation.

Benzyl Isothiocyanate and Resveratrol Synergistically Alleviate Dextran Sulfate Sodium-Induced Colitis in Mice.

The aim of our study was to investigate whether the combination of benzyl isothiocyanate (BITC) and resveratrol (RES) has a synergistic effect on the inhibition of inflammation in colitis. The results revealed that the BITC and RES combination (BITC_RES) was more effective than either substance alone at significantly alleviating the symptoms of dextran sodium sulfate (DSS)-induced colitis in mice, including the prevention of colon shortening and loss of body weight, a reduction in the disease activity index, and prevention of colon damage. Similarly, compared with the DSS group, BITC_RES reduced myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) levels in the mouse colon by 1.4-3.0-fold and 1.4-fold, respectively. In addition, the combination of BITC and RES upregulated the inflammatory factor IL-10 by 1.3- and 107.4-fold, respectively, compared to the individual BITC and RES groups, whereas the proinflammatory factors, including TNF-α, IL-1β, and IL-6, were downregulated by 1.1-7.4-, 0.7-3.6-, and 0.6-2.6-fold, respectively, in the BITC_RES group compared with the individual groups. Gut microbiome analysis indicated that BITC_RES remodeled the structure of gut bacteria at the phylum, family, and genus levels, upregulating the abundance of the phylum Bacteroidetes and the family Muribaculaceae and the genus norank_f_Muribaculaceae and downregulating the abundance of the phylum Firmicutes. Significant correlations between the relative levels of these proinflammatory cytokines and changes in the gut microbiota were found using Pearson's correlation analysis. BITC and RES exhibited synergistic effects by reshaping the gut microbiota and modulating the level of serum cellular inflammatory factors, thus exerting a protective effect against colitis.

A derivative of 3-(1,3-diarylallylidene)oxindoles inhibits dextran sulfate sodium-induced colitis in mice

BackgroundIA-0130 is a derivative of 3-(1,3-diarylallylidene)oxindoles, which is a selective estrogen receptor modulator (SERM). A previous study demonstrated that SERM exhibits anti-inflammatory effects on colitis by promoting the anti-inflammatory phenotype of monocytes in murine colitis. However, the therapeutic effects of oxindole on colitis remain unknown. Therefore, we evaluated the efficacy of IA-0130 on dextran sulfate sodium (DSS)-induced mouse colitis.MethodsThe DSS-induced colitis mouse model was established by administration of 2.5% DSS for 5 days. Mice were orally administered with IA-0130 (0.01 mg/kg or 0.1 mg/kg) or cyclosporin A (CsA; 30 mg/kg). Body weight, disease activity index score and colon length of mice were calculated and histological features of mouse colonic tissues were analyzed using hematoxylin and eosin staining. The expression of inflammatory cytokines and tight junction (TJ) proteins were analyzed using quantitative real-time PCR and enzyme-linked immunosorbent assay. The expression of interleukin-6 (IL-6) signaling molecules in colonic tissues were investigated using Western blotting and immunohistochemistry (IHC).ResultsIA-0130 (0.1 mg/kg) and CsA (30 mg/kg) prevented colitis symptom, including weight loss, bleeding, colon shortening, and expression of pro-inflammatory cytokines in colon tissues. IA-0130 treatment regulated the mouse intestinal barrier permeability and inhibited abnormal TJ protein expression. IA-0130 down-regulated IL-6 expression and prevented the phosphorylation of signaling molecules in colonic tissues.ConclusionsThis study demonstrated that IA-0130 suppressed colitis progression by inhibiting the gp130 signaling pathway and expression of pro-inflammatory cytokines, and maintaining TJ integrity.

Tauroursodeoxycholic Acid Reverses Dextran Sulfate Sodium-Induced Colitis in Mice via Modulation of Intestinal Barrier Dysfunction and Microbiome Dysregulation.

Ulcerative colitis (UC) is an immune-mediated inflammatory disease that can lead to persistent damage and even cancer without any intervention. Conventional treatments can alleviate UC symptoms but are costly and cause various side effects. Tauroursodeoxycholic acid (TUDCA), a secondary bile acid derivative, possesses anti-inflammatory and cytoprotective properties for various diseases, but its potential therapeutic benefits in UC have not been fully explored. Mice were subjected to colitis induction using 3% dextran sulfate sodium (DSS). The therapeutic effect of TUDCA was evaluated by body weight loss, disease activity index (DAI), colon length, and spleen weight ratio. Tissue pathology was assessed using H&E staining, while the levels of pro-inflammatory and anti-inflammatory cytokines in colonic tissue were quantified via ELISA. Tight junction proteins were detected by immunoblotting and intestinal permeability was assessed using fluorescein isothiocyanate (FITC)-dextran. Moreover, the gut microbiota was profiled using high-throughput sequencing of the 16S rDNA gene. TUDCA alleviated the colitis in mice, involving reduced DAI, attenuated colon and spleen enlargement, ameliorated histopathological lesions, and normalized levels of pro-inflammatory and anti-inflammatory cytokines. Furthermore, TUDCA treatment inhibited the downregulation of intestinal barrier proteins, including zonula occludens-1 and occludin, thus reducing intestinal permeability. The analysis of gut microbiota suggested that TUDCA modulated the dysbiosis in mice with colitis, especially for the remarkable rise in Akkermansia TUDCA exerted a therapeutic efficacy in DSS-induced colitis by reducing intestinal inflammation, protecting intestinal barrier integrity, and restoring gut microbiota balance. SIGNIFICANCE STATEMENT: This study demonstrates the potential therapeutic benefits of Tauroursodeoxycholic acid (TUDCA) in ulcerative colitis. TUDCA effectively alleviated colitis symptoms in mice, including reducing inflammation, restoring intestinal barrier integrity and the dysbiosis of gut microbiota. This work highlights the promising role of TUDCA as a potentially alternative treatment, offering new insights into managing this debilitating condition.

Bear Bile Powder Inhibits the Release of NLRP3 by Activating the cAMP/PKA/CREB Signaling Pathway to Treat Dextran Sulfate Sodium-induced Colitis in Mice

Bear Bile Powder Inhibits the Release of NLRP3 by Activating the cAMP/PKA/CREB Signaling Pathway to Treat Dextran Sulfate Sodium-induced Colitis in Mice

The immunomodulatory effects of paraprobiotic mixtures derived from novel probiotic isolates in dextran sodium sulfate-induced colitis in mice via MAPK pathway

IntroductionThe positive effects of paraprobiotic which are inviable components derived from probiotic strains, in a colitis model have been reported in some studies, although the precise mechanisms behind these effects have not been fully elucidated. Therefore, the objective of this study was to evaluate the beneficial anti-inflammatory effect of paraprobiotics derived from our native Bifidobacterium and Lactobacillus spp. In a colitis model as a safer product in comparison to probiotic, through the MAPK signaling pathway. MethodsColitis was induced by orally administering 2 % DSS to C57BL/6 mice. Alongside DSS, a mixture of paraprobiotics was administered via gavage. After two weeks, the mice were assessed using Disease Activity Index and histopathological scores. Moreover, the colonic specimens were analyzed to determine the expression of inflammatory markers using qRT-PCR. ResultsThe consumption of DSS resulted in alterations in body weight and the structure of the colon. However, the administration of the paraprobiotics mixture exhibited a significant improvement in DSS-induced colitis in mice through a reduction in body weight loss and an increase in the colon length. Furthermore, there were decreases in DAI and histopathological scores observed following this treatment. The administration of paraprobiotics led to a reduction in inflammation by downregulating the expression of MAPK-related genes that were induced by DSS. ConclusionThe findings demonstrate that presented paraprobiotic have a protective effect in a mouse model of DSS-induced colitis by mitigating the inflammatory response. The present study provides support for the development of paraprobiotics as a safe alternative therapeutic agent for IBD.