Sulfate Sodium-induced Colitis In Mice Research Articles

Possibility of alleviate dextran sulfate sodium-induced colitis in mice by modulate intestinal barrier function and gut microbiota with laminarin acetyl esters

Possibility of alleviate dextran sulfate sodium-induced colitis in mice by modulate intestinal barrier function and gut microbiota with laminarin acetyl esters

Segmental Regulation of Intestinal Motility by Colitis and the Adaptive Immune System in the Mouse Ileum and Colon.

Gastrointestinal motility disturbances are a hallmark of inflammatory bowel disease (IBD); however, their mechanisms remain unclear. This study used a dextran sulfate sodium-induced colitis mouse model, deficient in mature B and T lymphocytes, to assess intestinal motility and the role of the adaptive immune system in health and IBD. In healthy mice, the absence of adaptive lymphocytes reduced acetylcholine (ACh) sensitivity in the ileum. During colitis, it decreases motility by reducing the intensity and frequency of spontaneous contractions while increasing cholinergic responsiveness. In the proximal colon, adaptive immunity deficiency led to increased contractility and reduced ACh sensitivity in homeostasis, whereas colitis reduced contractile capacity. In the mid colon, immune-deficient mice had reduced ACh sensitivity in homeostasis and exacerbated contractile responses during colitis. In the distal colon, adaptive immunity loss reduced contractility in health and cholinergic responsiveness during colitis. These motility alterations were associated with altered acetylcholinesterase and M2/M3 muscarinic receptor expression. Notably, adaptive lymphocyte deficiency resulted in reduced tissue damage and lower tumor necrosis factor-α expression in the colon during colitis, paralleling intestinal motility changes. Overall, the adaptive immune system critically regulates motility and inflammation across different intestinal segments in IBD.

Lysosomes finely control macrophage inflammatory function via regulating the release of lysosomal Fe2+ through TRPML1 channel

Lysosomes are best known for their roles in inflammatory responses by engaging in autophagy to remove inflammasomes. Here, we describe an unrecognized role for the lysosome, showing that it finely controls macrophage inflammatory function by manipulating the lysosomal Fe2+—prolyl hydroxylase domain enzymes (PHDs)—NF-κB—interleukin 1 beta (IL1B) transcription pathway that directly links lysosomes with inflammatory responses. TRPML1, a lysosomal cationic channel, is activated secondarily to ROS elevation upon inflammatory stimuli, which in turn suppresses IL1B transcription, thus limiting the excessive production of IL-1β in macrophages. Mechanistically, the suppression of IL1B transcription caused by TRPML1 activation results from its modulation on the release of lysosomal Fe2+, which subsequently activates PHDs. The activated PHDs then represses transcriptional activity of NF-κB, ultimately resulting in suppressed IL1B transcription. More importantly, in vivo stimulation of TRPML1 ameliorates multiple clinical signs of Dextran sulfate sodium-induced colitis in mice, suggesting TRPML1 has potential in treating inflammatory bowel disease.

Studies on the alleviating effect of Bifidobacterium lactis V9 on dextran sodium sulfate-induced colitis in mice

BackgroundInflammatory bowel disease (IBD) has become a global public health problem with complex pathogenesis and limited therapeutic options. We aimed to investigate the potential mechanisms by which Bifidobacterium lactis V9 (V9) alleviated colitis in a dextran sodium sulfate-induced colitis model mice.MethodsMice were induced to develop colitis by drinking DSS solution to induce colitis. The expression of the relevant factors in the blood supernatant of the mice was determined by ELISA. RT-qPCR and Western blotting were used to detect mRNA and protein expression of target genes. The fecal microbiota was analyzed by 16S rRNA sequencing. Intestinal metabolites were analyzed by untargeted metabolomics;ResultsV9 effectively improved the overall symptoms of the colitis model mice. H&E showed that V9 re-stored the intestinal tissue structure. ELISA showed that V9 decreased the levels of IL-6, IL-22, and TNF-α and increased IL-10, SP, VIP, and 5-HT. V9 increased the expression of AHR, CYP1A1, MUC2, Claudin-3, Occludin, and ZO-1, and decreased 5-hydroxytryptamine transporter and Claudin-2. V9 increased the abundance of gut microbiota in colitis mice to promote the growth of beneficial bacteria. V9 increased tryptophan metabolites, and short-chain fatty acids, and improved gut inflammation.ConclusionV9 attenuates intestinal inflammation, improves the mucosal barrier, modulates intestinal microecology and exerts a protective effect in a mouse model of DSS-induced colitis.

Adhesive polyelectrolyte coating through UV-triggered polymerization on PLGA particles for enhanced drug delivery to inflammatory intestinal mucosa

Administering medication precisely to the inflamed intestinal sites to treat ulcerative colitis (UC), with minimized side effects, is of urgent need. In UC, the inflammation damaged mucosa contains a large number of amino groups which are positively charged, providing new opportunities for drug delivery system design. Here, we report an oral drug delivery system utilizing the tacrolimus-loaded poly (lactic-co-glycolic acid) (TAC/PLGA) particles with an adhesion coating by in situ UV-triggered polymerization of polyacrylic acid and N-hydroxysuccinimide (PAA-NHS). The negatively charged carboxyl groups effectively interact with the positively charged focal mucosa, and the NHS ester groups form the covalent bonds with the amino groups, thereby synergically enhancing the adhesion of the PLGA particles to the focal mucosa. Our findings reveal that, compared to the naked particles, the PAA-NHS coating increases the adhesion of particles to the inflammatory intestine. In a dextran sulfate sodium-induced acute colitis mouse model, the TAC/PLGA particles with PAA-NHS coating exhibits substantial retention of TAC within the inflammatory intestine, enhancing drug delivery efficiency and therapeutic effects. This approach holds promise for UC management, minimizing systemic side effects and optimizing therapeutic outcomes.Graphical abstract

A pectic polysaccharide from Lycium ruthenicum Murray alleviates dextran sulfate sodium-induced colitis in mice

A pectic polysaccharide from Lycium ruthenicum Murray alleviates dextran sulfate sodium-induced colitis in mice

The inflammatory bowel disease and gut microbiome are restored by employing metformin-loaded alginate-shelled microcapsules.

Inflammatory bowel disease (IBD) is a chronic or recurrent inflammatory disorder affecting various parts of the gastrointestinal tract. Metformin, a widely prescribed hypoglycemic drug for type 2 diabetes, has shown potential in reducing IBD risk. However, its oral administration faces significant challenges due to the harsh gastrointestinal environment, requiring higher or more frequent doses to achieve therapeutic effects, which increases the risk of side effects. To address this, we developed alginate-shelled hydrogel microcapsules with a thin oil layer for targeted intestinal delivery of metformin. The oil layer protects metformin from gastric acid and ensures its release specifically in the intestines. In a dextran sulfate sodium-induced colitis mouse model, metformin-loaded hydrogel microcapsules (MHM) significantly reduced disease activity, intestinal epithelial damage, and macrophage infiltration linked to pro-inflammatory cytokine factors. Additionally, MHM improved dysbiosis of specific bacterial genera, including Bacteroides vulgatus, Lactobacillus (L.) gasseri, L. reuteri, and L. intestinalis, optimizing the abundance and composition of microorganisms. These findings indicate that encapsulating metformin within alginate shelled-microcapsules with a thin oil layer presents a potential delivery system for IBD treatment.

Optimization of a green tea seed oil-loaded double-layer emulsion and its preventive effects on dextran sulfate sodium-induced colitis in mice.

Green tea seed oil (GTSO; Camellia sinensis) is rich in bioactive compounds and has great potential for preventing intestinal inflammation. Conversely, high-fat diets have been shown to promote or aggravate gastrointestinal inflammation, and the bioactive ingredients of GTSO face difficulty passing through the gastrointestinal tract while remaining intact. This study employed whey protein isolate (WPI) and sodium carboxymethyl cellulose (CMC-Na) to prepare a GTSO-loaded double-layer emulsion. The optimal parameters were as follows: WPI (2% w/w) and 35% oil phase for the primary emulsion preparation, CMC-Na (0.8% w/w) for the final emulsion, and 450W of ultrasonic power for homogenization. No significant changes in particle size or coalescence in the emulsions were observed after 30days of storage at 4°C. In addition, in a simulated gastrointestinal digestion system, more than 60% of the encapsulated GTSO was able to remain intact while passing through the gastric and small intestinal environment. In mice with dextran sulfate sodium-induced colitis, pretreatment with the GTSO emulsion significantly prevented the further development of colitis, whereas an empty-carrier-plus-free-GTSO treatment had no such protective effects and even tended to aggravate the disease. The results of the present study suggest that encapsulated GTSO is a reliable alternative approach for colitis prevention. PRACTICAL APPLICATION: The green tea seed oil-loaded double-layer emulsion demonstrates good storage stability when kept at 4°C, exhibits excellent slow-release performance, and achieves superior outcomes in the prevention of colitis. Our current study provides a reliable alternative approach for the prevention of colitis.

Elegant approach to intervention of homogalacturonan from the fruits of Ficus pumila L. in colitis: Unraveling the role of methyl esters and acetyl groups.

Oral administration of homogalacturonan (HG) has shown significant potential in anti-colitis activity, yet the therapeutic efficacy of naturally sourced HG still requires enhancement. Herein, HG from the fruits of Ficus pumila L. was modified by chemical methods and the intervention effect of modified HG with different degrees of methyl-esterification (DM) and acetylation (DA) on dextran sulfate sodium-induced colitis in mice was explored. Our results indicated that low-DM HG (DM3 and DM25) primarily mitigated colitis by reducing inflammation (TNF-α, IL-1β, IL-17, and IL-6), while high-DM HG (DM54 and DM94) primarily repaired the intestinal barrier. These effects may be attributed to the differential regulation of gut microbiota by HG with varying DM, such as Lachnospiraceae_NK4A136_group, Lactobacillus, Mucispirillum, Escherichia-Shigella, Bifidobacterium, and Bacteroides. Increased DA reduced the solubility of HG, showing limited anti-inflammatory response but unique advantages in intestinal barrier repair and microbiome regulation (Bifidobacterium, Candidatus_Saccharimonas, Lachnospiraceae_NK4A136_group, Mucispirillum, and Escherichia-Shigella). Furthermore, various structural parameters and substitution degrees showed no significant impact on HG's regulation of oxidative stress reactions. This study emphasized the importance of substituent effect in determining HG's functional role, providing a robust foundation for the design and development of functional polysaccharides for the prevention of intestinal inflammation and other related conditions.

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.

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

Ulcerative colitis is a chronic inflammatory disease closely associated with immune dysregulation. Zhiqiao (Fructus aurantii), the nearly mature fruit of Citrus aurantium L., is widely used in traditional dietary therapy for intestinal health. Here, we extracted and purified neohesperidin from Zhiqiao and explored its alleviative effects on dextran sulfate sodium-induced colitis and related inflammatory pathways in mice. The results showed that neohesperidin administration significantly ameliorated symptoms of colitis and reduced the accumulation of inflammatory cytokines in mouse tissues and serum. Decreases in the TLR4, MyD88, and NF-κB p65 mRNA expression levels indicated that activity of the TLR4/NF-κB signaling pathway was downregulated. Molecular docking results showed that neohesperidin occupies the lipopolysaccharide-binding pocket of MD-2 and binds to the interacting surface of TLR4/MD-2 and that of the subsequently formed homodimer, thereby disrupting recognition of inflammatory ligands by the TLR4-mediated pathway. Neohesperidin holds promise for the adjunctive treatment of ulcerative colitis.

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.

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.

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.