Sulfate Sodium-induced Colitis In Mice Research Articles

Narirutin mitigates dextrose sodium sulfate-induced colitis in mice by modulating intestinal flora

BackgroundUlcerative colitis (UC) is a prolonged inflammatory disease of the gastrointestinal tract. Current therapeutic options remain limited, underscoring the imperative to explore novel therapeutic strategies. Narirutin (NR), a flavonoid naturally present in citrus fruits, exhibits excellent anti-inflammatory effects in vitro, yet its in vivo efficacy, especially in UC, remains underexplored. ObjectiveThis work examined the effect of NR on dextrose sodium sulfate (DSS)-induced UC in mice in vivo, with a specific focus on the role of gut flora in it. MethodsThe effects of NR (10, 20, and 40 mg/kg) on DSS-induced UC in mice were investigated by monitoring changes in body weight, disease activity index (DAI) scores, colon length, and histological damage. Colonic levels of pro-inflammatory mediators, tight junction (TJ) proteins, and inflammation-related signaling pathway proteins were analyzed via enzyme-linked immunosorbent assay, western blot, and immunofluorescence. The role of gut microbiota in NR against colitis was analyzed through 16S rRNA sequencing, flora clearance assays, and fecal microbiota transplantation (FMT) assays. ResultsNR administration suppressed DSS-induced colitis as reflected in a decrease in body weight loss, DAI score, colon length shortening, and histological score. Furthermore, NR administration preserved the integrity of the DSS-induced intestinal barrier by inhibiting the reduction of TJ proteins (claudin3, occludin, and zonula occludens-1). Moreover, NR administration markedly repressed the activation of the toll-like receptor 4-mitogen-activated protein kinase/nuclear factor-κB pathway and reduced the amount of pro-inflammatory mediators in the colon. Importantly, the results of 16S rRNA sequencing showed that the intestinal flora of mice with colitis exhibited richer microbial diversity following NR administration, with elevated abundance of Lactobacillaceae (Lactobacillus) and decreased abundance of Bacteroidaceae (Bacteroides) and Shigella. In addition, the anti-colitis effect of NR almost disappeared after gut flora clearance. Further FMT assay also validated this gut flora-dependent protective mechanism of NR. ConclusionOur findings suggest that NR is a prospective natural compound for the management of UC by modulating intestinal flora.

Bazedoxifene attenuates dextran sodium sulfate-induced colitis in mice through gut microbiota modulation and inhibition of STAT3 and NF-κB pathways

Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract for which treatment options remain limited. In this study, we used a dual-luciferase-based screening of an FDA-approved drug library, identifying Bazedoxifene (BZA) as an inhibitor of the NF-κB pathway. We further investigated its therapeutic effects in a dextran sodium sulfate (DSS)-induced colitis model and explored its impact on gut microbiota regulation and the underlying molecular mechanisms. Our results showed that BZA significantly reduced DSS-induced colitis symptoms in mice, evidenced by decreased colon length shortening, lower histological scores, and increased expression of intestinal mucosal barrier-associated proteins, such as Claudin 1, Occludin, Zo-1, Mucin 2 (Muc2), and E-cadherin. Used independently, BZA showed therapeutic effects comparable to those of infliximab (IFX). In addition, BZA modulated the abundance of gut microbiota especially Bifidobacterium pseudolongum, and influenced microbial metabolite production. Crucially, BZA's alleviation of DSS-induced colitis in mice was linked to change in gut microbiota composition, as evidenced by in vivo gut microbiota depletion and fecal microbiota transplantation (FMT) mice model. Molecularly, BZA inhibited STAT3 and NF-κB activation in DSS-induced colitis in mice. In general, BZA significantly reduced DSS-induced colitis in mice through modulating the gut microbiota and inhibiting STAT3 and NF-κB activation, and its independent use demonstrated a therapeutic potential comparable to IFX. This study highlights gut microbiota's role in IBD drug development, offering insights for BZA's future development and its clinical applications.

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.

Clostridium butyricum isolated from giant panda can attenuate dextran sodium sulfate-induced colitis in mice.

Probiotics are beneficial to the intestinal barrier, but few studies have investigated probiotics from giant pandas. This study aims to explore the preventive effects of giant panda-derived Clostridium butyricum on dextran sodium sulfate (DSS)-induced colitis in mice. Clostridium butyricum was administered to mice 14 days before administering DSS treatment to induce enteritis. Clostridium butyricum B14 could more effectively prevent colitis in mice than C. butyricum B13. C. butyricum B14 protected the mouse colon by decreasing the histology index and serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels, which improved intestinal inflammation-related symptoms. In addition, the treatment led to the regulation of the expression of Tifa, Igkv12-89, and Nr1d1, which in turn inhibited immune pathways. The expression of Muc4, Lama3, Cldn4, Cldn3, Ocln, Zo1, Zo2, and Snai is related the intestinal mucosal barrier. 16S sequencing shows that the C. butyricum B14 significantly increased the abundance of certain intestinal probiotics. Overall, C. butyricum B14 exerted a preventive effect on colitis in mice by inhibiting immune responses, enhancing the intestinal barrier and increasing the abundance of probiotic species. Thus, C. butyricum B14 administration helps regulate the balance of the intestinal microecology. It can suppress immune pathways and enhance barrier-protective proteins.

Phlorotannins Isolated from Eisenia bicyclis and Lactobacillus casei Ameliorate Dextran Sulfate Sodium-Induced Colitis in Mice through the AhR Pathway

Ulcerative colitis (UC), an inflammatory bowel disease (IBD) linked to colon cancer, needs effective natural preventive and therapeutic strategies to alleviate its clinical course. This study investigated the combined effects of phlorotannins (TAs) isolated from Eisenia bicyclis (E. bicyclis) and Lactobacillus casei (LC) on inflammatory markers in UC, with a focus on the aryl hydrocarbon receptor (AhR) axis. In vitro experiments revealed anti-inflammatory effects of the phlorotannin fraction isolated from E. bicyclis, especially in synergy with LC. In vivo experiments showed that a synbiotic combination of TAs and LC mitigated DSS-induced colitis and reduced intestinal shortening and splenic hypertrophy. The TA and LC combination suppressed inflammatory factors (IL-6, TNF-α, Lipocalin 2), while activating tight junction genes (Muc2, Zo-1, Occludin, and Claudin1) and enhancing antioxidant capacity (Nrf2 and Nqo1 genes). Activation of the AhR pathway, which is crucial for regulating intestinal inflammation via IL-22, was evident with both phlorotannin alone and synbiotic administration. The combination of TAs and LC amplified the synergistic effect on intestinal immunity and microbiota, favoring beneficial species and optimizing the Firmicutes/Bacteroidetes ratio. Overall, synbiotic use demonstrated superior preventive effects against UC, suggesting its potential benefits for improving the gut immune system through gut microbiota-derived metabolites.

Geraniin Alleviates Inflammation in Caco-2 Cells and Dextran Sulfate Sodium-Induced Colitis Mice by Targeting IL-1β.

IL-1β is an important cytokine implicated in the progression of inflammatory bowel disease (IBD) and intestinal barrier dysfunction. The polyphenolic compound, geraniin, possesses bioactive properties, such as antitumor, antioxidant, anti-inflammatory, antihypertensive, and antiviral activities; however, its IL-1β-targeted anticolitis activity remains unclear. Here, we evaluated the inhibitory effect of geraniin in IL-1β-stimulated Caco-2 cells and a dextran sulfate sodium (DSS)-induced colitis mouse model. Geraniin blocked the interaction between IL-1β and IL-1R by directly binding to IL-1β and inhibited the IL-1β activity. It suppressed IL-1β-induced intestinal tight junction damage in human Caco-2 cells by inhibiting IL-1β-mediated MAPK, NF-kB, and MLC activation. Moreover, geraniin administration effectively reduced colitis symptoms and attenuated intestinal barrier injury in mice by suppressing elevated intestinal permeability and restoring tight junction protein expression through the inhibition of MAPK, NF-kB, and MLC activation. Thus, geraniin exhibits anti-IL-1β activity and anticolitis effect by hindering the IL-1β and IL-1R interaction and may be a promising therapeutic anti-IL-1β agent for IBD treatment.

Antcin-H, a natural triterpene derived from Antrodia cinnamomea, ameliorates dextran sulfate sodium-induced colitis in mice by inhibiting the NLRP3 inflammasome

Inflammatory bowel disease (IBD) comprises idiopathic intestinal disorders, including ulcerative colitis and Crohn's disease. Patients with IBD experience a significantly reduced quality of life, and effective management remains challenging. The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome controls the expression of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18. Abnormal activation of the NLRP3 inflammasome is a crucial factor in the pathogenesis of IBD, making it an attractive therapeutic target. We discovered that Antcin-H, a triterpene isolated from the unique medicinal fungus Antrodia cinnamomea found in Taiwan, effectively inhibits the NLRP3 inflammasome in macrophages and alleviates dextran sulfate sodium (DSS)-induced colitis in a mouse model. We noted that Antcin-H effectively suppresses the NLRP3 inflammasome in macrophages by diminishing reactive oxygen species production, alleviating mitochondrial damage, and reducing apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization. Importantly, these effects are achieved without impacting NF-κB activation. Oral administration of Antcin-H improved symptoms such as diarrhea, bloody stool, weight loss, colon length shortening, and splenomegaly in DSS-treated mice. Antcin-H inhibits colonic expression of NLRP3, ASC, active caspase-1, IL-1β, IL-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, myeloperoxidase, C-X-C motif chemokine ligand 1, and cyclooxygenase-2 in DSS-treated mice. Furthermore, Antcin-H modulates the colonic expression of long non-coding RNAs involved in the regulation of NLRP3 inflammasome activation. These results indicate that Antcin-H has the potential to improve IBD by reducing colonic inflammation and suppressing NLRP3 inflammasome activation.

Efficacy and Mechanism of the Action of Live and Heat-Killed Bacillus coagulans BC198 as Potential Probiotic in Ameliorating Dextran Sulfate Sodium-Induced Colitis in Mice.

Inflammatory bowel disease alters the gut microbiota, causes defects in mucosal barrier function, and leads to dysregulation of the immune response to microbial stimulation. This study investigated and compared the efficacy of a candidate probiotic strain, Bacillus coagulans BC198, and its heat-killed form in treating dextran sulfate sodium-induced colitis. Both live and heat-killed B. coagulans BC198 increased gut barrier-associated protein expression, reduced neutrophil and M1 macrophage infiltration of colon tissue, and corrected gut microbial dysbiosis induced by colitis. However, only live B. coagulans BC198 could alleviate the general symptoms of colitis, prevent colon shortening, and suppress inflammation and tissue damage. At the molecular level, live B. coagulans BC198 was able to inhibit Th17 cells while promoting Treg cells in mice with colitis, reduce pro-inflammatory MCP-1 production, and increase anti-inflammatory IL-10 expression in the colonic mucosa. The live form of B. coagulans BC198 functioned more effectively than the heat-killed form in ameliorating colitis by enhancing the anti-inflammatory response and promoting Treg cell accumulation in the colon.

Toll-like receptor 3 signaling drives enteric glial cells against dextran sulfate sodium-induced colitis in mice.

The activation of toll-like receptor 3 (TLR3) has been reported to attenuate astrocytes injury in central nervous system, but its effect on enteric glial cells (EGCs) remains unknown. Here, we confirmed that the residence of EGCs was regulated by TLR3 agonist (polyinosinic-polycytidylic acid, PIC) or TLR3/dsRNA complex inhibitor in dextran sulfate sodium (DSS)-induced mice. In vitro, TLR3 signaling prevented apoptosis in EGCs and drove the secretion of EGCs-derived glial cell line-derived neurotrophic factor, 15-hydroxyeicosatetraenoic acid and S-nitrosoglutathione. PIC preconditioning enhanced the protective effects of EGCs against the dysfunction of intestinal epithelial barrier and the development of colitis in DSS-induced mice. Interestingly, PIC stimulation also promoted the effects of EGCs on converting macrophages to an M2-like phenotype and regulating the levels of inflammatory cytokines, including IL-1β, TNF-α and IL-10, in DSS-induced mice. These findings imply that TLR3 signaling in EGCs may provide a potential target for the prevention and treatment of colitis.

Microencapsulation as a Protective Strategy for Sialylated Immunoglobulin G: Efficacy in Alleviating Symptoms of Dextran Sulfate Sodium-Induced Colitis in Mice and Potential Mechanisms.

Sialylated immunoglobulin G (IgG) is a vital glycoprotein in breast milk with the ability to promote the growth of Bifidobacterium in gut microbiota and relieve inflammatory bowel disease (IBD) symptoms in vitro. Here, it was found that the microcapsules with sialylated IgG could protect and release sialylated IgG with its structure and function in the intestine. Furthermore, the sialylated IgG microcapsules alleviated the clinical symptoms (body weight, feed quantity, and colon length loss), decreased disease activity index score, suppressed the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IFN-γ, and MCP-1) and endotoxin (lipopolysaccharide), and enhanced the intestinal mucosal barrier (Claudin1, Muc2, Occludin, and ZO-1) in dextran sulfate sodium (DSS)-induced colitis mice. Additionally, the sialylated IgG microcapsules improved the gut microbiota by increasing the relative abundance of critical microbe Bifidobacterium bifidum and promoted the production of short-chain fatty acids (SCFAs). Correlation analysis indicated that the key microbes were strongly correlated with pro-inflammatory factors, clinical symptoms, tight junction protein, and SCFAs. These findings suggest that the sialylated IgG microcapsules have the potential to be used as a novel therapeutic approach for treating IBD.

The intestinal microbiota modulates the transcriptional landscape of iNKT cells at steady-state and following antigen exposure

Invariant Natural Killer T (iNKT) cells are unconventional T cells that respond to microbe-derived glycolipid antigens. iNKT cells exert fast innate effector functions that regulate immune responses in a variety of contexts, including during infection, cancer, or inflammation. The roles these unconventional T cells play in intestinal inflammation remain poorly defined and vary based on the disease model and species. Our previous work suggested that the gut microbiota influenced iNKT cell functions during dextran sulfate sodium-induced colitis in mice. In this study, we show that iNKT cell homeostasis and response following activation are altered in germ-free mice. Using prenatal fecal transplant in specific pathogen-free mice, we show that the transcriptional signatures of iNKT cells at steady state and following αGC-mediated activation in vivo are modulated by the microbiota. Our data suggest that iNKT cells sense the microbiota at homeostasis independently of their TCR. Finally, iNKT cell transcriptional signatures are different in male and female mice. Collectively, our findings suggest that sex and the intestinal microbiota are important factors that regulate iNKT cell homeostasis and responses. A deeper understanding of microbiota-iNKT cell interactions and the impact of sex could improve the development of iNKT cell-based immunotherapies.

Preventive effect of Lacticaseibacillus rhamnosus 2016SWU.05.0601 and its postbiotic elements on dextran sodium sulfate-induced colitis in mice.

Microbial-based therapies are one of the hotspots in the field of ulcerative colitis research. The lactic acid bacteria and their postbiotics occupy a key position in microbial therapies, however, the mechanism by which they alleviate ulcerative colitis in mice is unknown. We investigated the effects of Lacticaseibacillus rhamnosus 2016SWU.05.0601 (Lr-0601) and its postbiotics on male Kunming mice with dextran sulfate sodium salt (DSS)-induced ulcerative colitis (UC). The results showed that Lr-0601 significantly alleviated the deterioration of UC and restored the expression of intestinal mechanical barrier proteins. In addition, Lr-0601 significantly reduced the expression of inflammatory cytokines in the body and regulated the expression of key regulatory genes of the NF-κB-iNOS/COX-2 signaling pathway in colon tissues to a large extent. Our results suggest that supplementation with Lr-0601 and its postbiotics can effectively prevent DSS-induced UC and have a beneficial effect on intestinal health, which also provides new insights and research bases for the prevention as well as the treatment of ulcerative colitis and other diseases related to intestinal barrier dysfunction and other diseases.

Circadian Rhythm Perturbation Aggravates Gut Microbiota Dysbiosis in Dextran Sulfate Sodium-Induced Colitis in Mice.

Circadian rhythm disruption is increasingly considered an environmental risk factor for the development and exacerbation of inflammatory bowel disease. We have reported in a previous study that nychthemeral dysregulation is associated with an increase in intestinal barrier permeability and inflammation in mice with dextran sulfate sodium (DSS)-induced colitis. To investigate the effect of circadian rhythm disruption on the composition and diversity of the gut microbiota (GM), sixty male C57BL/6J mice were initially divided to two groups, with the shifted group (n = 30) exposed to circadian shifts for three months and the non-shifted group (n = 30) kept under a normal light-dark cycle. The mice of the shifted group were cyclically housed for five days under the normal 12:12 h light-dark cycle, followed by another five days under a reversed light-dark cycle. At the end of the three months, a colitis was induced by 2% DSS given in the drinking water of 30 mice. Animals were then divided into four groups (n = 15 per group): sham group non-shifted (Sham-NS), sham group shifted (Sham-S), DSS non-shifted (DSS-NS) and DSS shifted (DSS-S). Fecal samples were collected from rectal content to investigate changes in GM composition via DNA extraction, followed by high-throughput sequencing of the bacterial 16S rRNA gene. The mouse GM was dominated by three phyla: Firmicutes, Bacteroidetes and Actinobacteria. The Firmicutes/Bacteroidetes ratio decreased in mice with induced colitis. The richness and diversity of the GM were reduced in the colitis group, especially in the group with inverted circadian rhythm. Moreover, the GM composition was modified in the inverted circadian rhythm group, with an increase in Alloprevotella, Turicibacter, Bacteroides and Streptococcus genera. Circadian rhythm inversion exacerbates GM dysbiosis to a less rich and diversified extent in a DSS-induced colitis model. These findings show possible interplay between circadian rhythm disruption, GM dynamics and colitis pathogenesis.

Anthocyanin Extracted from Purple Sweet Potato Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice by Suppressing Pyroptosis and Altering Intestinal Flora Structure.

The objective of this study was to examine the impact and underlying mechanisms of pelargonidin-3-galactoside (Pg3gal) produced from purple sweet potatoes on colonic inflammation induced by dextran sulfate sodium (DSS) in a murine model of ulcerative colitis (UC). C57BL/6J mice were categorized into four groups (n = 6 per group): DSS+Pg3gal, control, control+Pg3gal, and DSS. Colitis was induced by providing free access to 3% DSS for 10 days. The DSS+Pg3gal model mice received DSS concurrently with intragastric Pg3gal (25 mg/kg). The health of the mice was carefully monitored on a regular basis, and scores for the Disease Activity Index (DAI) were documented. A histological assessment was conducted using hematoxylin and eosin staining to evaluate the extent of mucosal injury present. The expression levels of IL-6, NLRP3, ASC, cleaved-Caspase-1, TNF-α, N-GSDMS, and cleaved-IL-1β proteins were evaluated by Western blot analysis. The process of 16S rRNA sequencing was carried out to examine the composition and relative abundance of gut microbiotas within the intestines of the mice. The DAI results revealed that Pg3gal significantly attenuated the DSS-induced UC in mice. In addition, it successfully alleviated the decline in colon size, improved the condition of colonic tissue, and significantly inhibited the production of proinflammatory cytokines, such as IL-6, IL-1β, and TNF-α, in the colon tissues. Additionally, Pg3gal modulated the DSS-induced imbalanced gut microbiota, as evidenced by decreased Proteobacteria and Deferribacteres and simultaneous elevation in Firmicutes, Bacteroidetes, and Verrucomicrobia. In summary, Pg3gal alleviated DSS-induced UC by inhibiting pyroptosis in intestinal epithelial cells and enhancing the structural integrity of the gut microbiota.

Porcine Intestinal Mucosal Peptides Target Macrophage-Modulated Inflammation and Alleviate Intestinal Homeostasis in Dextrose Sodium Sulfate-Induced Colitis in Mice.

Porcine intestinal mucosal proteins are novel animal proteins that contain large amounts of free amino acids and peptides. Although porcine intestinal mucosal proteins are widely used in animal nutrition, the peptide bioactivities of their enzymatic products are not yet fully understood. In the present study, we investigated the effect of porcine intestinal mucosal peptides (PIMP) on the RAW264.7 cell model of LPS-induced inflammation. The mRNA expression of inflammatory factors (interleukin 6, tumor necrosis factor-α, and interleukin-1β) and nitrous oxide levels were all measured by quantitative real-time PCR and cyclooxygenase-2 protein expression measured by Western blot. To investigate the modulating effect of PIMP and to establish a model of dextran sodium sulfate (DSS)-induced colitis in mice, we examined the effects of hematoxylin-eosin staining, myeloperoxidase levels, pro-inflammatory factor mRNA content, tight junction protein expression, and changes in intestinal flora. Nuclear factor κB pathway protein levels were also assessed by Western blot. PIMP has been shown in vitro to control inflammatory responses and prevent the activation of key associated signaling pathways. PIMP at doses of 100 and 400 mg/kg/day also alleviated intestinal inflammatory responses, reduced tissue damage caused by DSS, and improved intestinal barrier function. In addition, PIMP at 400 mg/kg/day successfully repaired the dysregulated gut microbiota and increased short-chain fatty acid levels. These findings suggest that PIMP may positively influence inflammatory responses and alleviate colitis. This study is the first to demonstrate the potential of PIMP as a functional food for the prevention and treatment of colitis.

D-alanine inhibits murine intestinal inflammation by suppressing IL-12 and IL-23 production in macrophages.

Free D-amino acids, which have different functions from L-amino acids, have recently been discovered in various tissues. However, studies on the potential interactions between intestinal inflammation and D-amino acids are limited. We examined the inhibitory effects of D-alanine on the pathogenesis of intestinal inflammation. We investigated serum D-amino acid levels in 40 patients with ulcerative colitis and 34 healthy volunteers. For 7 d, acute colitis was induced using dextran sulfate sodium in C57BL/6J mice. Plasma D-amino acid levels were quantified in mice with dextran sulfate sodium-induced colitis, and these animals were administered D-alanine via intraperitoneal injection. IFN-γ, IL-12p35, IL-17A, and IL-23p19 mRNA expression in the colonic mucosa was measured using real-time PCR. In vitro proliferation assays were performed to assess naïve CD4+ T cell activation under Th-skewing conditions. Bone marrow cells were stimulated with mouse macrophage-colony stimulating factor to generate mouse bone marrow-derived macrophages. Serum D-alanine levels were significantly lower in patients with ulcerative colitis than in healthy volunteers. Dextran sulfate sodium-treated mice had significantly lower plasma D-alanine levels than control mice. D-alanine-treated mice had significantly lower disease activity index than control mice. IFN-γ, IL-12p35, IL-17A, and IL-23p19 mRNA expression levels were significantly lower in D-alanine-administered mice than in control mice. D-alanine suppressed naïve T cell differentiation into Th1 cells in vitro and inhibited the production of IL-12p35 and IL-23p19 in bone marrow-derived macrophages. Our results suggest that D-alanine prevents dextran sulfate sodium-induced colitis in mice and suppresses IL-12p35 and IL-23p19 production in macrophages.

Effect of by BIOVITA 3 (a Blend of Three Probiotics) on Dextran Sulfate Sodium-Induced Colitis in Mice

Effect of by BIOVITA 3 (a Blend of Three Probiotics) on Dextran Sulfate Sodium-Induced Colitis in Mice

Gut Microbiota-mediated Alleviation of Dextran Sulfate Sodium-induced Colitis in Mice

Background and AimsGut dysbiosis characterized by an imbalanced microbiota is closely involved in the pathogenesis of a widespread gastrointestinal inflammatory disorder, inflammatory bowel disease (IBD). However, it is unclear how the complex intestinal microbiota affects development or resistant of mucosal inflammation. Our aim was to investigate the impact of the gut microbiota on susceptibility in a mouse model of ulcerative colitis. MethodsWe compared the susceptibility to dextran sulfate sodium (DSS)-induced colitis of inbred BALB/c mice obtained from the three main distributors of laboratory animals in Japan. Clinical symptoms of the colitis and the faecal microbiota were assessed. Cohousing approach was used to identify whether the gut microbiota is a primary factor determining disease susceptibility. ResultsHere, we showed differences in the susceptibility of BALB/c mice from the vendors to DSS colitis. Analysis of the gut microbiota using 16S rRNA sequencing revealed clear separation of the gut microbial composition among mice from the vendors. Notably, the abundance of the phylum Actinobacteriota was strongly associated with disease activity. We also observed the expansion of butyrate-producing Roseburia species in mice with decreased susceptibility of the disease. Further cohousing experiments showed that variation in clinical outcomes was more correlated with the gut microbiota than genetic variants among substrains from different suppliers. ConclusionsA BALB/c substrain that was resistant to DSS-induced colitis was observed, and the severity of DSS-induced colitis was mainly influenced by the gut microbiota. Targeting butyrate-producing bacteria could have therapeutic potential for ulcerative colitis.

Aged oolong tea alleviates dextran sulfate sodium-induced colitis in mice by modulating the gut microbiota and its metabolites

In this study, the mechanism of aged oolong tea (AOT) to alleviate colitis was investigated in terms of microbiome, metabolome, and fecal microbiota transplantation (FMT). AOT storage period could alleviate colitis in mice and there were some differences in AOT between storage periods, especially AOT-10. AOT improves UC by modulating oxidative stress and inflammatory factors and upregulating intestinal tight junction protein expression (Occludin, Claudin-1, ZO-1 and MUC2), which is associated with the recovery of gut microbiota. FMT and targeted metabolomics further demonstrate that the anti-inflammatory effects of AOT can reshape the gut microbiota through faecal bacterial transfer. Anti-inflammatory effects are exerted through the stimulation of metabolic pathways associated with amino acid, fatty acid and bile acid metabolites. Importantly, the study identified key bacteria (e.g., Sutterella, Clostridiaceae_Clostridium, Mucispirillum, Oscillospira and Ruminococcus) for the development and remission of inflammation. Conclusively, AOT may have great potential in the future adjuvant treatment of colitis.

Fraxetin ameliorates symptoms of dextran sulphate sodium-induced colitis in mice

Ulcerative colitis (UC) is one of the primary inflammatory bowel diseases (IBDs) and causes a serious threat to human public health around the world. Currently, there are no proven safe and effective treatment options to treat UC. Fraxetin (Fxt) is a widely recognized antioxidant and anti-inflammatory legume derived from ash bark. In the present study, we investigated the protective effect and mechanism of Fxt on UC. Our results showed that Fxt significantly attenuated the body weight, colon length reduction, tissue damage, and disease activity index induced by dextran sodium sulphate (DSS). Moreover, the DSS-induced activation of the NF-κB pathway and NLRP3 inflammasomes was inhibited, and the inflammatory response was reduced. Fxt restored gut barrier function by increasing the number of goblet cells and the levels of tight junction proteins (ZO-1 and occludin). In addition, Fxt can alter the intestinal microbiota by enhancing the diversity of the microbiota, increasing the relative abundance of beneficial bacteria and inhibiting the growth of harmful bacteria. These results revealed that Fxt alleviates DSS-induced colitis by modulating the inflammatory response, enhancing epithelial barrier integrity and regulating the gut microbiota. This study may provide a scientific basis for the potential therapeutic effect of Fxt in the prevention of colitis and other related diseases.