Sulfate Sodium-induced Colitis In Mice Research Articles

Deinococcus radiodurans R1 Lysate Induces Tolerogenic Maturation in Lipopolysaccharide-Stimulated Dendritic Cells and Protects Dextran Sulfate Sodium-Induced Colitis in Mice.

Deinococcus radiodurans is an extremophilic bacterium that can thrive in harsh environments. This property can be attributed to its unique metabolites that possess strong antioxidants and other pharmacological properties. To determine the potential of D. radiodurans R1 lysate (DeinoLys) as a pharmacological candidate for inflammatory bowel disease (IBD), we investigated the anti-inflammatory activity of DeinoLys in bone marrow-derived dendritic cells (BMDCs) and a colitis mice model. Lipopolysaccharide (LPS)-stimulated BMDCs treated with DeinoLys exhibited alterations in their phenotypic and functional properties by changing into tolerogenic DCs, including strongly inhibited proinflammatory cytokines (TNF-α and IL-12p70) and surface molecule expression and activated DC-induced T cell proliferation/activation with high IL-10 production. These phenotypic and functional changes in BMDCs induced by DeinoLys in the presence of LPS were abrogated by IL-10 neutralization. Furthermore, oral administration of DeinoLys significantly reduced clinical symptoms against dextran sulfate sodium-induced colitis, including body weight loss, disease activity index, histological severity in colon tissue, and lower myeloperoxidase level in mice. Our results establish DeinoLys as a potential anti-inflammatory candidate for IBD therapy.

Ulva prolifera Polysaccharide-Manganese Alleviates Inflammation and Regulates Microbiota Composition in Dextran Sulfate Sodium-Induced Colitis Mice.

Manganese (Mn) deficiency exacerbates colitis symptoms, whereas diet supplemented with inorganic Mn merely maintains colon length in experimental colitis. In the present study, a new form of Mn, Ulva prolifera polysaccharide cheated-Mn (PMn) was used and its treatment effects on dextran sulfate sodium (DSS)-induced colitis were investigated. Male C57BL/6 mice were orally administrated with 3.5% DSS to induce colitis. Then, the colitis mice were treated with PBS or PMn for 7 days. The results showed that PMn administration help retrieve the body weight loss and intestinal morphology damage, and alleviate apoptosis and inflammatory responses in colitis mice. Moreover, PMn administration decreased intestinal infiltration as indicated by decreased concentration of myeloperoxidase and eosinophil peroxidase. Importantly, PMn retrieved the increased abundance of Firmicutes and the decreased abundance of Bacteroidetes caused by DSS, suggested its beneficial roles in regulating microbiota composition in mice with colon inflammation. Gut microbiota composition at the genus level in the mice administrated with PMn was similar to those in control mice, whereas they were clearly distinct from DSS-treated mice. These results support the potential therapeutic role of PMn in the treatment of intestinal colitis and microbes may play critical roles in mediating its effects.

Perindopril/Ambrosin Combination Mitigates Dextran Sulfate Sodium-Induced Colitis in Mice: Crosstalk between Toll-Like Receptor 4, the Pro-Inflammatory Pathways, and SIRT1/PPAR-γ Signaling.

Colitis is one of the inflammatory states that affect the intestinal wall and may even predispose to malignancy due to chronic irritation. Although the etiology of colitis is not yet fully explored, a combination of genetic and environmental factors is strongly incriminated. Perindopril is an angiotensin-converting enzyme inhibitor that is used for the management of a wide range of cardiovascular diseases. Ambrosin is a sesquiterpene lactone that was proven to have beneficial effects in disorders characterized by inflammatory nature. The objective of this study is to make a comparison between the effects of perindopril or ambrosin on dextran sulfate sodium (DSS)-induced colitis in mice and to explore the effect of their combination. The present findings indicate that each ambrosin or perindopril alone or in combination is able to ameliorate oxidative stress and suppress the proinflammatory pathways in the colonic tissues of DSS-treated mice via mechanisms related to toll-like receptor 4/nuclear factor kappa B signaling and modulation of peroxisome proliferator-activated receptor gamma/sirtuin-1 levels. In addition, each ambrosin or perindopril alone or in combination inhibits apoptosis and augments the mediators of autophagy in DSS-treated mice. These effects are reflected in the amelioration of the histopathological and electron microscopic changes in the colonic tissues. Interestingly, the most remarkable effects are those encountered with the perindopril/ambrosin combination compared to the groups treated with each of these agents alone. In conclusion, the perindopril/ambrosin combination might represent an effective modality for mitigation of the pathogenic events and the clinical sequelae of colitis.

Trans-10-Hydroxy-2-Decenoic Acid Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice via Regulating the Inflammasome-Mediated Pyroptotic Pathway and Enhancing Colonic Barrier Function.

The objective of this study is to explore the effects of 10-hydroxy-2-decenoic acid (10-HDA), the major fatty acid in royal jelly, on dextran sodium sulfate (DSS)-induced mice ulcerative colitis (UC) and its potential mechanism of action. Forty male C57BL/6 mice are randomly divided into five experimental groups: control, DSS, DSS + 25 (or 100)mgkg-1 d-1 10-HDA, and DSS + 200mgkg-1 d-1 mesalazine (ME). UC is induced in mice using 2.5% DSS in drinking water for 7 days. During the induction, these UC mice are orally administrated 10-HDA or ME per day.Meanwhile, lipopolysaccharide (LPS)/adenosine-triphosphate (ATP)-stimulated THP1 cells are used as a model to test the effects of 10-HDA. 10-HDA reduces DSS-induced pathological damage, reactive oxygen species (ROS) accumulation, neutrophil infiltration, and cytokine production in colonic tissue. Compared with the DSS group, the expressions of thioredoxin interacting protein (TXNIP), NOD-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), cysteinyl aspartate specific proteinase-1 (Caspase-1), gasdermin-D (GSDMD), N-terminal domain of gasdermin-D (N-GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in the colon are decreased after administration of 10-HDA. 10-HDA also elevates the barrier integrity and the expressions of zonula occludens-1 (ZO-1) and Occludin in colonic epithelium exposed to DSS. In THP1 cells, the inflammasome-mediated pyroptosis induced by LPS/ATP is inhibited by 10-HDA pretreatment. 10-HDA alleviates DSS-induced colitis by regulating the NLRP3 inflammasome-mediated pyroptotic pathway and enhancing colonic barrier function.

Lactobacillus casei Strain Shirota Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Increasing Taurine-Conjugated Bile Acids and Inhibiting NF-κB Signaling via Stabilization of IκBα.

Inflammatory bowel disease (IBD) is a chronic progressive intestinal inflammatory disease, characterized by an altered gut microbiota composition and accompanying alterations in circulatory bile acids. Increasing evidence supports the beneficial effect of probiotics intake on health. Introduction of probiotics to the intestines can modulate gut microbiota composition and in turn regulate the host immune system and modify the inflammatory response. Probiotics can also improve intestinal barrier function and exhibit a positive impact on host physiological and pathological conditions via gut microbiota-derived metabolites. Previous studies have demonstrated that Lactobacillus casei strain Shirota (LcS) treatment could inhibit clinical manifestation of colitis in dextran sulfate sodium (DSS)-induced mice, however, the underlying mechanisms remain unknown. In this study, we employed the DSS-induced acute colitis mouse model to investigate the anti-inflammatory effects of LcS and related mechanisms. Administration of LcS ameliorated the severity of DSS-induced colitis and enhanced intestinal integrity via induction of mucin-2 and occludin expression in colons. Fecal microbiota analysis showed that LcS increased the relative abundance of beneficial bacterial species in colitic mice, whereas the relative abundance of pathobionts was reduced. Additionally, LcS treatment modulated circulating bile acid profiles in colitic mice. In mice treated with LcS, we identified increased levels of primary taurine-conjugated bile acids, including taurocholic acid (TCA) and taurochenodeoxycholic acid (TCDCA). LcS treatment also increased the levels of secondary taurine-conjugated bile acids, including taurodeoxycholic acid (TDCA) and tauroursodeoxycholic acid (TUDCA). Moreover, LcS treatment exhibited a suppressive effect on the hydroxylated primary bile acids α-muricholic acid (α-MCA) and β-muricholic acid (β-MCA). We further demonstrated that LcS treatment suppressed the expression of pro-inflammatory mediators interferon-gamma (IFN-γ) and nitric oxide (NO), and increased the expression of the anti-inflammatory mediator interleukin-10 (IL-10) in colon tissues, potentially as a result of altered bile acid profiles. Mechanistically, we showed that LcS treatment suppressed the activation of nuclear factor-kappa B (NF-κB) signaling via stabilization of inhibitor of NF-κB alpha (IκBα). Altogether, we have demonstrated the therapeutic effects of LcS in DSS-induced colitis, providing new insights into its effect on bile acid metabolism and the related anti-inflammatory mechanisms. Our findings provide support for the application of LcS in the treatment of IBD.

Development of Early-Life Gastrointestinal Microbiota in the Presence of Antibiotics Alters the Severity of Acute DSS-Induced Colitis in Mice.

ABSTRACTEarly-life gastrointestinal microbiota development is crucial for physiological development and immunological homeostasis. In the current study, perinatal microbiota and the development of gastrointestinal microbiota in different early-life periods (perinatal, lactation, and postweaning nutrition periods) were explored by using an antibiotic-interfered mouse model and a dextran sulfate sodium-induced colitis mouse model. Gut microbiota samples were collected from mother mice and litters. The results of 16S rRNA gene sequences suggested that microbiota in the gastrointestinal system were present in prenatal fetal mice, and microbiota structures in different parts of the gastrointestinal system of the fetal mice were similar to those in the corresponding gut parts of maternal mice. Microbiota in mucus samples from different regions exhibited higher diversity at birth than at other periods and varied substantially over time with diet change. Moreover, antibiotic treatment in early life affected the composition and diversity of gastrointestinal microbiota in adult mice and enhanced susceptibility to experimental colitis in mice, particularly in the lactation period. This approach of exploring gut microbiota evolution is hoped to provide an enhanced view of how resident microbiota develop in early life, which in turn might facilitate understanding of gut microbiota and related diseases.IMPORTANCE This study investigated resident microbiota in the whole gastrointestinal (GI) tract to explore gut microbiota development in early life and found that early-life antibiotic exposure exacerbated alterations in gut microbiota and murine dextran sulfate sodium (DSS)-induced colitis. Furthermore, the presence of bacteria in the GI tract of mice before birth and the importance of the lactation period in GI microbiota development were confirmed.

Immunomodulatory effects of Companilactobacillus allii WiKim39 and Lactococcus lactis WiKim0124 isolated from kimchi on lipopolysaccharide-induced RAW264.7 cells and dextran sulfate sodium-induced colitis in mice

• Vegetable juice was fermented with Companilactobacillus allii WiKim39 or Lactococcus lactis Wikim0124 isolated from kimchi. • VJ + WiKim39 and VJ + WiKim0124 exhibited anti-inflammatory effects in LPS-induced RAW264.7 cells. • VJ + WiKim39 and VJ + WiKim0124 exhibited anti-inflammatory effects in DSS-induced colitis in mice. • The anti-inflammatory effects of VJ + WiKim39 and VJ + WiKim0124 were established via the NF-kB pathway in vitro and in vivo . Lactic acid bacteria (LAB) isolated from kimchi has beneficial antioxidant, anti-obesity, anti-cancer and immunomodulatory effects. Here, we investigated the immunomodulatory effects of vegetable juice (VJ) fermented with Companilactobacillus allii WiKim39 (VJ + WiKim39) or Lactococcus lactis WiKim0124 (VJ + WiKim0124) isolated from kimchi, in vitro and in vivo . Nitric oxide (NO) production and levels of inflammatory markers were significantly lower in lipopolysaccharide (LPS)-stimulated RAW264.7 cells treated with heat-inactivated VJ + WiKim39 and heat-inactivated VJ + WiKim0124 than in untreated cells ( P < 0.05). In mice with dextran sulfate sodium (DSS)-induced colitis, oral administration of VJ + WiKim39 and VJ + WiKim0124 attenuated DSS-induced decrease in colon length and mucosal epithelia. Moreover, VJ + WiKim39 and VJ + WiKim0124 significantly downregulated several inflammatory markers ( P < 0.05). Overall, WiKim39 and WiKim0124 showed immunomodulatory activity in vitro and in vivo and thus, they could be used in health promoting fermented foods.

Immuno‐Engineered Nanodecoys for the Multi‐Target Anti‐Inflammatory Treatment of Autoimmune Diseases

Overactivated T cells and overproduced pro-inflammatory cytokines form a self-amplified signaling loop to continuously exacerbate the dysregulated inflammatory response and propel the progression of autoimmune diseases (AIDs). Herein, immuno-engineered nanodecoys (NDs) based on poly(lactic-co-glycolic acid) nanoparticles coated with programmed death-ligand 1 (PD-L1)-expressing macrophage membrane (PRM) are developed to mediate multi-target interruption of the self-promoted inflammatory cascade in AIDs. The PRM collected from IFN-γ-treated RAW 264.7 cells possesses elevated surface levels of adhesion molecule receptors and pro-inflammatory cytokine receptors, and, thus, systemically administered PRM NDs afford higher accumulation level in inflamed tissues and stronger scavenging efficiency toward multiple pro-inflammatory cytokines. More importantly, IFN-γ treatment induces remarkable PD-L1 expression on PRM, thereby allowing PRM NDs to bind membrane-bound programmed death-1 (PD-1) on CD4+ T cell surfaces or neutralize free soluble PD-1, which reconstructs the PD-1/PD-L1 inhibitory axis to suppress CD4+ T cell activation and restore immune tolerance. As such, PRM NDs provoke potent and cooperative anti-inflammatory and immune-suppressive efficacies to alleviate autoimmune damages in Zymosan A-induced arthritis mice and dextran sulfate sodium-induced ulcerative colitis mice. This study provides an enlightened example for the immuno-engineering of cell-membrane-based NDs, rendering promising implications into the treatment of AIDs via multi-target immune-modulation.

Chitosan Oligosaccharides Alleviate Colitis by Regulating Intestinal Microbiota and PPARγ/SIRT1-Mediated NF-κB Pathway.

Chitosan oligosaccharides (COS) have been shown to have potential protective effects against colitis, but the mechanism underlying this effect has not been fully elucidated. In this study, COS were found to significantly attenuate dextran sodium sulfate-induced colitis in mice by decreasing disease activity index scores, downregulating pro-inflammatory cytokines, and upregulating Mucin-2 levels. COS also significantly inhibited the levels of nitric oxide (NO) and IL-6 in lipopolysaccharide-stimulated RAW 264.7 cells. Importantly, COS inhibited the activation of the NF-κB signaling pathway via activating PPARγ and SIRT1, thus reducing the production of NO and IL-6. The antagonist of PPARγ could abolish the anti-inflammatory effects of COS in LPS-treated cells. COS also activated SIRT1 to reduce the acetylation of p65 protein at lysine 310, which was reversed by silencing SIRT1 by siRNA. Moreover, COS treatment increased the diversity of intestinal microbiota and partly restored the Firmicutes/Bacteroidetes ratio. COS administration could optimize intestinal microbiota composition by increasing the abundance of norank_f_Muribaculaceae, Lactobacillus and Alistipes, while decreasing the abundance of Turicibacte. Furthermore, COS could also increase the levels of propionate and butyrate. Overall, COS can improve colitis by regulating intestinal microbiota and the PPARγ/SIRT1-mediated NF-κB pathway.

Oral benzo[a]pyrene administration attenuates dextran sulfate sodium-induced colitis in mice

Benzo[a]pyrene (BaP) is an environmental pollutant produced by combustion processes and is present in grilled foods as well as in tobacco smoke. BaP acts as an agonist for the aryl hydrocarbon receptor (AHR), and is metabolized by AHR-inducing enzymes. BaP metabolism can result in either detoxification or metabolic activation, the latter leads to an increased risk of disease, particularly lung cancer and cardiovascular disease, in a context-dependent manner. Although AHR activation has been thought to protect against inflammatory bowel disease, it remains unknown whether BaP exerts a protective or deleterious effect on colitis. In this study, we examined the effect of oral BaP administration on colitis induced by dextran sulfate sodium (DSS) in mice, an animal model of inflammatory bowel disease. BaP administration attenuated weight loss, shortening of the colon, disease activity index scores, and histological damage in DSS-induced colitis mice. BaP also suppressed colonic expression of inflammation-associated genes and plasma interleukin-6 secretion induced by DSS treatment. BaP-DNA adduct formation, a marker of BaP metabolic activation, was not enhanced in the colon after DSS treatment. Thus, oral BaP exerts an anti-inflammatory effect on DSS-induced colitis, without the toxicity associated with metabolic activation. The results provide insights into the disease-specific roles of BaP.

Ginger Extract Decreases Susceptibility to Dextran Sulfate Sodium-Induced Colitis in Mice Following Early Antibiotic Exposure.

Background: Intestinal microbial colonization in early life plays a crucial role in immune development and mucosal homeostasis in later years. Antibiotic exposure in early life increases the risk of inflammatory bowel disease (IBD). Ginger acts like a prebiotic and has been used in traditional Chinese medicine for colitis. We investigated the protective effect of ginger against dextran sulfate sodium (DSS)-induced colitis in mice exposed to antibiotic in their early years.Methods: A weaned mouse model exposed to azithromycin (AZT) for 2 weeks was used to mimic antibiotic exposure in childhood among humans. A diet containing ginger extract was administered to mice for 4 weeks after antibiotic exposure. The susceptibility to DSS-induced colitis was evaluated in terms of weight loss, disease activity index (DAI) score, colon length, colitis biomarkers, and intestinal barrier function. The gut microbiota was analyzed in terms of 16S rRNA levels.Results: Ginger extract prevented weight loss, colon shortening, inflammation, and intestinal barrier dysfunction in mice exposed to antibiotics in early life. Ginger increased the bacterial diversity and changed the abundance of bacterial belonging to family Peptococcaceae and Helicobacter species to modulate microbiota structure and composition adversely affected by early antibiotic exposure.Conclusion: Ginger has a protective effect in potentially decreasing the susceptibility to colitis in mice exposed to antibiotics early in life.

Differential effects of various dietary proteins on dextran sulfate sodium-induced colitis in mice.

Chronic colitis is a risk factor for colorectal cancer (CRC) development in both animals and humans. Previously, we reported that a diet rich in protein (with casein as the protein source) significantly increased the risk of mouse CRC development in a dose-dependent manner. In this study, we investigated the effects of different protein sources on the risk of colitis development. Balb/c mice were divided into 7 experimental groups: 20% casein (20C), 20C-dextran sulfate sodium (DSS), 40% casein-DSS (40CD), 40% whey protein-DSS (40WD), 40% soy protein-DSS (40SD), 40% white meat-DSS (40WMD), and 40% red meat-DSS (40RMD). Mice were fed an experimental diet for 4 wk and received 3% DSS in their drinking water for 6 days during the 4th wk of the experimental period. Compared to other groups, the 40CD group showed the most aggravated colitis with increased disease activity and inflammatory markers. In the 40RMD group, interleukin (IL)-6 levels were the highest among all the groups. The 40SD group showed conflicting effects, for example, elevated mortality and disease activity but decreased nitric oxide (NO) levels. The 40WD group showed attenuated colitis with increased IL-10 levels and decreased NO levels. The 40WMD group showed conflicting effects, including decreased NO levels and elevated fecal lipocalin-2 and IL-6 levels. These results suggest that, at levels of 40% in the diet, casein and red meat exacerbate colitis, whereas whey protein mitigates it the most effectively.

Tuberous Sclerosis Complex 1 Deficiency in Macrophages Promotes Unclassical Inflammatory Response to Lipopolysaccharide In Vitro and Dextran Sodium Sulfate-Induced Colitis in Mice.

Human tuberous sclerosis (TSC) is mainly caused by genetic mutations of tuberous TSC1or TSC2. Recent studies found that TSC1 deficiency promoted classical M1 macrophage polarization. However, whether TSC1 regulates other inflammatory cytokine expression in lipopolysaccharidem (LPS)-stimulated macrophages is unknown. Herein, we studied the cytokine expression profile of wild-type (WT) and TSC1-deleted macrophages after LPS stimulation in vitro and the pathogenesis of dextran sodium sulfate (DSS)-induced colitis in mice with myeloid-specific TSC1 deletion (TSC1cKO mice). We found that TSC1-deficient macrophages exhibited the enhanced secretion of interleukin-17A (IL-17A), IL-17F, and interferon-gamma (IFN-γ) in response to LPS stimulation in vitro. This is in contrast to LPS-stimulated WT macrophages, which usually do not. Importantly, TSC1cKO mice exhibited exacerbated DSS-induced acute colitis with severer symptoms. MTOR deletion or rapamycin treatment significantly reversed the enhanced expressions of IL-17A, IL-17F, and IFN-γ in LPS-stimulated TSC1-deficient macrophages in vitro and rescued the enhanced DSS-induced colitis in TSC1cKO mice, indicating that TSC1 deficiency increased these cytokine productions in an mTOR-dependent manner. RNA-sequencing and molecular studies indicated that TSC1 deficiency enhanced the aerobic glycolysis process and the activities of mTOR-STAT3-RORγT pathway in LPS-stimulated macrophages. Inhibition of aerobic glycolysis, STAT3, or RORγT reversed IL-17 and IFN-γ expression in LPS-treated TSC1-deficient macrophages. Thus, TSC1 is essential for macrophages to shut down IL-17A, IL-17F, and IFN-γ expression during LPS stimulation by suppressing the aerobic glycolysis process and mTOR-STAT3, RORγT, and T-bet pathways. The present study uncovered the key role of TSC1 in shutting down IL-17A, IL-17F, and IFN-γ expressions in LPS-treated macrophages.

Epoxymicheliolide Prevents Dextran Sulfate Sodium-Induced Colitis in Mice by Inhibiting TAK1-NF-κB Pathway and Activating Keap1-NRF2 Signaling in Macrophages

Epoxymicheliolide Prevents Dextran Sulfate Sodium-Induced Colitis in Mice by Inhibiting TAK1-NF-κB Pathway and Activating Keap1-NRF2 Signaling in Macrophages

A β-N-acetylhexosaminidase Amuc_2109 from Akkermansia muciniphila protects against dextran sulfate sodium-induced colitis in mice by enhancing intestinal barrier and modulating gut microbiota.

Inflammatory bowel disease (IBD) is associated with the microbial composition of the gut and its metabolites. Akkermansia muciniphila is a probiotic that exerts a significant alleviative or therapeutic effect on host enteritis. This study was designed to determine the protective effect and potential mechanism underlying the secretion of β-acetylaminohexosidase (Amuc_2109) by A. muciniphila against dextran sulfate sodium (DSS)-induced colitis in mice. C57BL/6 mice were gavaged with Amuc_2109 for 21 days, and during the last seven days of treatment, they drank DSS dissolved in their drinking water to induce colitis. Our results showed that supplementation with Amuc_2109 improved DSS-induced colitis as evidenced by lowered disease activity index (DAI) scores, reduced weight loss, increased colon length, and inhibited oxidative stress. In addition, Amuc_2109 inhibited the overexpression of inflammatory cytokines (TNF-α, IL-1β, IL-6) and the NLR family pyrin domain containing 3 (NLRP3) inflammasome in DSS-induced colitis. Furthermore, supplementation with Amuc_2109 also restored the mRNA expression of tight junction proteins (ZO-1, occludin, claudin-1). Further analysis of fecal microbial 16S rRNA sequences showed that Amuc_2109 reshaped the intestinal microbiota. While the anti-inflammatory effects of Amuc_2109 were only manifested with the wild-type protein, the anti-inflammatory effects were completely lost after the mutation of its key catalytic amino acids rendered Amuc_2109 inactive. In summary, these findings demonstrate the potential of Amuc_2109, as a therapeutic agent for ulcerative colitis. We posit that it will provide additional assistance in the prevention and treatment of mucus layer-related diseases such as ulcerative colitis.

Therapeutic effect of indirubin-loaded bovine serum albumin nanoparticules on ulcerative colitis.

Indirubin is considered to have promising potential in the treatment of ulcerative colitis (UC). However, poor aqueous solubility and low bioavailability limit its clinical application. We produced indirubin-loaded bovine serum albumin nanoparticles (INPs) and characterized their drug encapsulation efficiency, drug-loading capacity, capacity to release indirubin in vitro and short-term physical stability. We also investigated the pharmacokinetics of INPs in mice. We then compared the curative effects of INPs and indirubin against dextran sulfate sodium-induced colitis in mice and 3D cultured biopsies from patients with UC. In the mouse model, the outcomes of INP treatment, including the disease activity index and serous levels of interleukin (IL)-1β and IL-10, were significantly different from those of indirubin treatment. Similarly, when we administered INPs and indirubin to the ex vivo colonic tissues of patients with UC, the effect of INPs was stronger than that of indirubin for most antioxidant and anti-inflammatory biomarkers. The results of both the animal trial and ex vivo experiment indicate that the therapeutic effect of indirubin was further enhanced by the carrier system, making it a highly promising medical candidate for UC.

Orphan G protein-coupled receptor GPR35 contributes to the pathogenesis of dextran sulfate sodium-induced colitis in mice.

Orphan G protein-coupled receptor GPR35 contributes to the pathogenesis of dextran sulfate sodium-induced colitis in mice.

Fermented egg-milk beverage alleviates dextran sulfate sodium-induced colitis in mice through the modulation of intestinal flora and short-chain fatty acids.

Fermented egg-milk beverage (FEMB) can alleviate the symptoms of intestinal diseases by regulating intestinal flora and supplying nutrition. This study investigated the protective effect of FEMB on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. The results showed that FEMB relieved the UC mice's pathological abnormalities and colonic inflammation, and restructured the intestinal flora composition simultaneously. After FEMB treatment for 14 days, the body weight of the mice rose and the disease activity index (DAI) value decreased. Furthermore, the length and form of colons in the UC mice were notably restored. Inflammatory cells decreased or disappeared, and goblet cells and crypt were enriched and modified. 16S rRNA gene sequencing results demonstrated that FEMB treatment could increase the abundance of beneficial bacteria in the cecum content of mice, including unclassified_f_Lachnospiraceae and Lactobacillus. Moreover, probiotics that can increase the content of short-chain fatty acids (SCFAs) may contribute to inflammation alleviation. An increase in amino acids was observed in our experiment, which may benefit nutritional supplements. In conclusion, FEMB treatment can alleviate the damage of DSS-induced colitis in Balb/c mice. This study provides a theoretical basis for both the relief of inflammation and the application of FEMB.

Isomaltulose alleviates acute colitis via modulating gut microbiota and the Treg/Th17 balance in mice.

Food-grade isomaltulose exhibits significant modulation of gut microbiota and its metabolites in healthy populations. This study further explored the preventive therapeutic effect and anti-colitis potential of isomaltulose on dextran sulfate sodium-induced colitis in mice. Our results suggested that isomaltulose played a significant role in preventing colon shortening, reducing intestinal epithelial destruction and inhibiting inflammatory cell infiltration. Meanwhile, the isomaltulose supplement greatly reduced the production of pro-inflammatory cytokines and restored the balance between T helper type 17 (Th17) cells and regulatory T (Treg) cells. Pathway enrichment analysis for differentially expressed genes (DEGs) also indicated that the anti-inflammatory effect of isomaltulose was closely related to intestinal immunity. Moreover, the disturbed gut microbiota in ulcerative colitis (UC) was partially restored after treatment with isomaltulose. These results suggest that isomaltulose is a promising therapeutic agent for the prevention and adjunctive treatment of UC by maintaining intestinal immune homeostasis and remodeling the gut microbiota.

Bile Salt Hydrolase of &lt;i&gt;Lactobacillus Plantarum&lt;/i&gt; Plays an Important Role in the Amelioration of Dextran Sulfate Sodium-Induced Colitis in Mice

Bile Salt Hydrolase of &lt;i&gt;Lactobacillus Plantarum&lt;/i&gt; Plays an Important Role in the Amelioration of Dextran Sulfate Sodium-Induced Colitis in Mice