Reveal the pharmacodynamic substances and mechanism of an edible medicinal plant Rhodiola crenulate in DSS-induced colitis through plasma pharmacochemistry and metabolomics

Rhodiola crenulate is the edible medicinal herbal medicine widely used for altitude sickness in China.Interestingly,our previous work has found that R.crenulate extract(RCE)could significantly improve the pathology associated with dextran sulfate sodium-induced colitis.Thus,the current research aims to reveal the pharmacodynamic material basis of RCE,as well as its mechanism against colitis.The chemical characterization of RCE was performed by UHPLC-HR-MS,through which a total of 88 constituents were identified.Meanwhile,our results also found 29 constituents absorbed into blood and 8 metabolized absorbable compounds.The decreased flavonoids prototype and the elevated sulfated products of phenols were observed under pathophysiological conditions of colitis.The metabolomics study revealed that colitis caused the alternation of fatty acid metabolism,steroid hormone biosynthesis and bile acid metabolism.Correspondingly,RCE could prevent colitis by improving fatty acid metabolism and secondary bile acid metabolism.

Lactobacillus from fermented bamboo shoots prevents inflammation in DSS-induced colitis mice via modulating gut microbiome and serum metabolites

Fermented bamboo shoots(FBS)is a region-specific food widely consumed in Southwestern China,with Lactobacillus as the predominant fermenting bacteria.However,the probiotic potential of Lactobacillus derived from FBS reminds largely unexplored,especially for diseases with a low prevalence in areas consuming FBS,namely,inflammatory bowel disease.In this study,Lactiplantibacillus pentosus YQ001 and Lentilactobacillus senioris YQ005 were screening by in vitro probiotic tests to further investigate the probioticlike bioactivity in dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)mouse.They exhibited more positive probiotic effects than Lactobacillus rhamnosus GG in preventing intestinal inflammatory response.The results revealed that both strains improved the abundance of deficient intestinal microbiota in UC mice,including Muribaculaceae and Akkermansia.In the serum metabolome,they modulated the DSS-disturbed levels of metabolites,with significant increment of cinnamic acid.Meanwhile,they reduced the expression levels of interleukin-1β(IL-1β),interleukin-6(IL-6)inflammatory factors and increased zonula occludens-1(ZO-1),Occludin,and cathelicidin-related antimicrobial peptide(CRAMP)in the colon.Consequently,these results demonstrated that Lactobacillus spp.isolates derived from FBS showed promising probiotic activity based on the gut microbiome homeostasis modulation,anti-inflammation and intestinal barrier protection in UC mice.

Anti-inflammatory Activity of Mollugin on DSS-induced Colitis in Mice

We aimed to explore the anti-infammatory bactivity of mollugin extracted from Rubia cordifolia L,a traditional Chinese medicine,on dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)in mice.Thirty C57BL/6 mice were divided into a control group(n=6),a model group(n=6),and three experimental groups(40,20,10 mg/kg of mollugin,n=6 each).DSS solution(3%)was given to mice in the model group and experimental groups from day 4 to day 10 to induce the mouse UC model.Mice in the experimental groups were intragastrically administrated mollugin from day 1 to day 10.Animals were orally given distilled water in the control group for the whole experiment time and in the model group from day 1 to day 3.The changes in colon pathology were detected by hematoxylin and eosin(HE)staining.Interleukin-1β(IL-1β)in the serum,and tumor necrosis factor-α(TNF-α)and interferon-γ(IFN)in the tissues were measured by enzyme linked immunosorbent assay.Expression levels of Toll-like receptor 4(TLR4)and myeloid differentiation factor 88 in the colon tissues were detected by immunohistochemistry.Results showed that mollugin could significantly reduce weight loss and the disease activity index in the DSS-induced UC mouse model.HE examinations demonstrated that mollugin treatment effectively improved the histological damage(P<0.05).The overproduction of IL-Iβand TNF-α was remarkably inhibited by mollugin treatment at doses of 20 and 40 mg/kg(P<0.05).Additionally,the levels of TLR4 in colon tissues were significantly reduced in mollugin-treated groups compared with the DSS group.Our findings demonstrated that mollugin ameliorates DSS-induced UC by inhibiting the production of pro-inflammatory chemocytokines.

Preserved egg white alleviates DSS-induced colitis in mice through the reduction of oxidative stress,modulation of inflammatory cytokines,NF-κB,MAPK and gut microbiota composition

Traditional Chinese preserved egg products have exhibited some anti-inflammatory effects,but their mechanisms of action remain unknown.This study aimed to investigate the anti-inflammatory effects of preserved egg white(PEW)treatment on dextran sulfate sodium(DSS)-induced colitis in mice and the underlying mechanisms.The results showed that treatment with PEW in mice with DSS-induced colitis for 14 days effectively improved the clinical signs,inhibited the secretion and gene expression of pro-inflammatory cytokines,and reduced myeloperoxidase(MPO)activity and oxidative stress levels.In addition,western blotting results showed that PEW significantly suppressed DSS-induced phosphorylation levels of nuclear factor-kappa B(NF-κB)p65 and p38 mitogen-activated protein kinase(MAPK)in colon tissues of mice with colitis.PEW also enhanced the production of short-chain fatty acids(SCFAs)and modulated gut microbiota composition in mice with DSS-induced colitis,including increasing the relative abundance of beneficial bacteria Lachnospiraceae,Ruminococcaceae and Muribaculaceae,and reducing the relative abundance of harmful bacteria Proteobacteria.Taken together,our study demonstrated that preserved egg white could alleviate DSS-induced colitis in mice through the reduction of oxidative stress,modulation of inflammatory cytokines,NF-κB,MAPK and gut microbiota composition.

Non-peptidyl low molecular weight radical scavenger IAC attenuates DSS-induced colitis in rats

AIM:To investigate the effects of the free radical scavenger bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl) decandioate(IAC) in the dextran sodium sulphate(DSS) experimental model of ulcerative colitis.METHODS:Colitis was induced in Sprague Dawley male rats by administration of 5% DSS in drinking water.IAC(30 mg/kg,lipophilic or hydrophilic form) was administered daily(orally or ip) for 6 d until sacrifice.Colonic damage was assessed by means of indirect(Disease Activity Index score) and direct measures(macroscopic and microscopic scores) and myeloperoxidase(MPO)activity.Neutrophil infiltration within the tissue and glutathione S-transferase activity were also investigated.RESULTS:DSS-induced colitis impaired body weight gain and markedly increased all inflammatory parameters.Six-day treatment with lipophilic IAC significantly reduced intestinal damage caused by inflammation,induced a down-regulation in MPO activity(0.72 ± 0.12 and 0.45 ± 0.12 with lipophilic IAC po and ip,respectively,vs 1.10 ± 0.27 in untreated DSS colitis animals) and minimized DSS-induced neutrophil infiltration,while hydrophilic IAC administered orally did not ameliorate DSS-induced damage.CONCLUSION:These results support the hypothesis that reactive oxygen metabolites contribute to inflammation and that the radical scavenger IAC has therapeutic potential in inflammatory bowel disease.

Effect of sodium alginate-based hydrogel loaded with lutein on gut microbiota and inflammatory response in DSS-induced colitis mice

In order to effectively deliver lutein to the inflamed colon and better exert its pharmacological activity,this paper constructed a sodium alginate hydrogel-based delivery system loaded with lutein nanoparticles,evaluated the regulation on the expression and secretion of related inflammatory factors in mice with colitis,and its impact on intestinal microbial environment.The results showed that comparing lutein crystal and its nanoparticle,lutein hydrogel alleviated dextran sodium sulfate(DSS)-induced colitis in mice more effectively by adjusting fecal heme content,colon tissue damage,and inflammatory factor levels.Moreover,lutein hydrogel increased the expression of intestinal tight junction proteins zonula occluden-1(ZO-1),claudin-1 and occludin to maintain the integrity of the intestinal-barrier,inhibited the nuclear factor-κB(NF-κB)pathway and reduced expression and secretion of inflammatory factors including tumour necrosis factor-α(TNF-α),inducible nitric oxide synthase(iNOS),NOD-like receptors 3(NLRP3)and interleukin(IL)-1β.In addition,the intestinal microbial environment of mice with colitis was improved by down-regulating the relative abundance of Desulfovibrionaceae and up-regulating the relative abundance of Erysipelotrichaceae and Rikenellaceae.As a slow-release carrier to load lutein nanoparticles,sodium alginate-based hydrogel has potential application prospect.

Impact of Bifidobacterium longum NSP001 on DSS-induced colitis in conventional and humanised mice

Most scientific investigations regarding inflammatory bowel disease(IBD)pathogenesis or therapeutic strategies use dextran sulfate sodium(DSS)-induced models performed on mice.However,differences between human and animal microbiota may confound the data reproducibility from rodent experiments to clinical trials.In this study,the intervention effects of Bifidobacterium longum NSP001 on DSS-induced colitis were investigated using mice colonized with either native or humanised microbiota.Disorders in disease activity index(DAI),morphology and histology of colon tissue,intestinal permeability,and secretion of MPO,TNF-αand IL-6 were ameliorated by daily intake of live B.longum NSP001 cells in both conventional and humanised colitis mice.But the abnormal thymus index,and colonic production of ZO-1 and iNOS were improved only in colitis mice treated with B.longum NSP001 and humanised microbiome.The accumulation of acetic acid and propionic acid in colon microbiome,and the optimization of primary bile acid biosynthesis and glycerophospholipid metabolism pathways in cecum commensals were likely to explain the beneficial effects of B.longum NSP001.These data revealed that intestinal microbiome baseline would possibly affect the manifestation features of interventions by probiotics or dietary components and highlighted the necessity to include humanised microbiome while investigating potential therapeutic strategies based on rodent models.

Cooperation of Wnt/β-catenin and Dll1-mediated Notch pathway in Lgr5-positive intestinal stem cells regulates the mucosal injury and repair in DSS-induced colitis mice model

Background:Lgr5-positive cells located in the basal layer of crypts have self-regenerative and proliferative differentiation potentials of intestinal stem cells(ISCs),maintaining a balance of regeneration-repair in mucosal epithelium.However,the mechanisms of mucosal repair that are regulated by ISCs in ulcerative colitis(UC)remain unclear.Method:Colon tissues from patients with UC were collected to testβ-catenin and Notch1 expression by using Western blot and quantitative real-time polymerase chain reaction(PCR).β-catenin^(fl/fl) mice,β-cateninTg mice,and Dll1tm1 Gos mice were used to cross with Lgr5-EGFP-IRES-creERT2 mice to generate mice of different genotypes,altering the activation of Wnt/β-catenin and Dll1-mediated Notch signaling in ISCs in vivo.Dextran sulfate sodium(DSS)was used to induce a colitis mice model.Intestinal organoids were isolated and cultured to observe the proliferation and differentiation levels of ISCs.Result:β-catenin and Notch1 expression were significantly increased in the inflamed colon tissues from patients with UC.Wnt/β-catenin activation and Dll1-mediated Notch pathway inhibition in Lgr5-positive stem cells promoted the expressions of E-cadherin,CK20,and CHGA in colonic organoids and epithelium,implying the promotion of colonic epithelial integrity.Activation of Wnt/β-catenin and suppression of Dll1-mediated Notch pathway in Lgr5-positive ISCs alleviated the DSS-induced intestinal mucosal inflammation in mice.Conclusions:Lgr5-positive ISCs are characterized by self-renewal and high dividend potential,which play an important role in the injury and repair of intestinal mucosa.More importantly,the Wnt/β-catenin signaling pathway cooperates with the Notch signaling pathway to maintain the function of the Lgr5-positive ISCs.

Structural characteristics of phenylboronic acid-modified astaxanthin ester and its effect on DSS-induced ulcerative colitis by blocking reactive oxygen species and maintaining intestinal homeostasis

A novel and reactive oxygen species(ROS)responsive astaxanthin phenylboronic acid derivative(AstaDPBA)was constructed by grafting phenylboronic acid(PBA)onto astaxanthin succinate diester(AstaD),and its chemical structure and physicochemical property were identified.AstaD-PBA could effectively improve the ROS quenching ability in the lipopolysaccharide(LPS)-induced RAW264.7 cell inflammation model.Then,the bioactivity of AstaD-PBA was studied by 4 zebrafish ROS-responsive infl ammatory models induced by LPS,copper(Cu^(2+)),high-fat diet,and dextran sodium sulfate(DSS).The results suggest that AstaD-PBA might have high biosafety and the best effect on ulcerative colitis(UC)induced by DSS.Furtherly,AstaDPBA significantly alleviated and treated weight loss and colonic shrinkage,inhibited infl ammatory cytokines,and maintained microbiota homeostasis to improve UC in C57BL/6J mice.Alistipes and Oscillibacter were expected to be considered UC marker fl ora according to the Metastats analysis and Pearson correlation Mantel test(P<0.01)of 16S rRNA gene sequencing data.In conclusion,AstaD-PBA has been promised to be a functional compound to improve UC and maintain intestinal microbiota homeostasis.

Initial gut microbiota structure affects sensitivity to DSS-induced colitis in a mouse model

The dextran sulfate sodium (DSS)-induced colitis model is a widely applied mouse model, but controversial results have been obtained from experiments using the same mouse strain under the same conditions. Because the gut microbiota play an important role in DSS-induced colitis, it is essential to evaluate the influence of the initial gut microbiota in this model. Here, we identified significant variations in the initial gut microbiota of different batches of mice and found that the initial intestinal microbiota had a profound influence on DSS-induced colitis. We performed three independent trials using the same C57BL/6J mouse model with DSS treatment and used high-throughput 16S rRNA gene sequencing to analyze the gut microbiota. We found that the structure and composition of the gut microbiota in mice with severe colitis, as compared with mice with milder colon damage, had unique features, such as an increase in Akkermansia bacteria and a decrease in Barnesiella spp. Moreover, these varied gut bacteria in the different trials also showed different responses to DSS treatment. Our work suggests that, in studies using mouse models, the gut microbiota must be considered when examining mechanisms of diseases, to ensure that comparable results are obtained.

Application of Saccharomyces boulardii in combination with sulfasalazine in ulcerative colitis patients demonstrates significant effectiveness

BACKGROUND Ulcerative colitis(UC)is a complex inflammatory bowel disease,and its etiology and pathogenesis remain incompletely elucidated.AIM To analyze the effects of Saccharomyces boulardii in combination with sulfasalazine on intestinal microbiota and intestinal barrier function in patients with UC.METHODS A retrospective analysis of clinical data from 127 UC patients admitted to our hospital between January 2021 and January 2023 was conducted.All patients met complete inclusion and exclusion criteria.Based on the treatment interventions received,they were divided into a control group(n=63)and an observation group(n=64).Both groups of patients received routine treatment upon admission.The control group received sulfasalazine in addition to routine interventions,while the observation group received a combination of Saccharomyces boulardii on the basis of the control group’s treatment.The clinical efficacy,improvement in symptoms,modified Baron endoscopic scores,quality of life“inflammatory bowel disease questionnaire(IBDQ)”,levels of intestinal microbial indicators(such as Lactobacillus,Bifidobacterium,Enterococcus,and Escherichia coli),intestinal mucosal barrier function indicators[diamine oxidase(DAO),lipopolysaccharide(LPS),D-lactic acid(D-LA)],and adverse reaction occurrences were compared between the two groups.RESULTS(1)Clinical efficacy:The total effective rate in the control group was 79.37%,while in the observation group,it was 93.75%,significantly higher than that of the control group(P<0.05);(2)Improvement in symptoms:The observation group showed significantly lower relief time for abdominal pain,diarrhea,rectal bleeding,fever symptoms,and mucosal healing time compared to the control group(P<0.05);(3)Baron endoscopic scores and IBDQ scores:Before treatment,there was no significant difference in Baron endoscopic scores and IBDQ scores between the two groups(P>0.05).However,after treatment,the observation group showed significantly lower Baron endoscopic scores and higher IBDQ scores compared to the control group(P<0.05);(4)Levels of intestinal microbial indicators:Before treatment,there was no significant difference in the levels of Lactobacillus,Bifidobacterium,Enterococcus,and Escherichia coli between the two groups(P>0.05).After treatment,the levels of Lactobacillus and Bifidobacterium in the observation group were significantly higher than those in the control group,while the levels of Enterococcus and Escherichia coli were significantly lower than those in the control group(P<0.05);(5)Levels of intestinal mucosal barrier function indicators:Before treatment,there was no significant difference in the levels of DAO,LPS,and D-LA between the two groups(P>0.05).However,after treatment,the levels of DAO,LPS,and D-LA in the observation group were significantly lower than those in the control group(P<0.05);and(6)Occurrence of adverse reactions:The incidence of adverse reactions in the control group was 9.52%,while in the observation group,it was 10.94%.There was no significant difference in the occurrence of adverse reactions between the two groups(P>0.05).CONCLUSION The application of Saccharomyces boulardii in combination with sulfasalazine in UC patients demonstrates significant effectiveness.Compared to sole sulfasalazine intervention,the combined application of Saccharomyces boulardii further promotes the relief of relevant symptoms in patients,alleviates intestinal mucosal inflammation,and improves the quality of life.Its action may be related to rectifying the imbalance in intestinal microbiota and improving intestinal mucosal barrier function.Moreover,the combined use of Saccharomyces boulardii does not increase the risk of adverse reactions in patients,indicating a higher level of medication safety and advocating for its clinical promotion and application.

Early identification and multidisciplinary management of immune checkpoint inhibitors associated colitis can improve patient outcomes

Currently,the use of immune checkpoint inhibitors(ICIs)has shown notable clinical efficacy in treating various malignant tumors,significantly improving patient prognosis.However,while ICIs enhance the body’s anti-tumor effects,they can also trigger immune-related adverse events(irAEs),with ICI-associated colitis being one of the more prevalent forms.This condition can disrupt treatment,necessitate drug discontinuation,and adversely affect therapeutic outcomes.In severe cases,irAEs may even become life-threatening.A recent case report by Hong et al highlights the importance of vigilance for ICI-associated colitis in patients experiencing symptoms such as diarrhea and abdominal pain,which can arise both during and even after completion of ICI treatment.Early identification,multidisciplinary management,and continuous monitoring of patients are essential steps to further improve outcomes.

Keratin 1 modulates intestinal barrier and immune response via kallikrein kinin system in ulcerative colitis

BACKGROUND External factors in ulcerative colitis(UC)exacerbate colonic epithelial permea-bility and inflammatory responses.Keratin 1(KRT1)is crucial in regulating these alterations,but its specific role in the progression of UC remains to be fully eluci-dated.AIM To explore the role and mechanisms of KRT1 in the regulation of colonic epithelial permeability and inflammation in UC.METHODS A KRT1 antibody concentration gradient test,along with a dextran sulfate sodium(DSS)-induced animal model,was implemented to investigate the role of KRT1 in modulating the activation of the kallikrein kinin system(KKS)and the cleavage of bradykinin(BK)/high molecular weight kininogen(HK)in UC.RESULTS Treatment with KRT1 antibody in Caco-2 cells suppressed cell proliferation,induced apoptosis,reduced HK expression,and increased BK expression.It further downregulated intestinal barrier proteins,including occludin,zonula occludens-1,and claudin,and negatively impacted the coagulation factor XII.These changes led to enhanced activation of BK and HK cleavage,thereby intensifying KKS-mediated inflammation in UC.In the DSS-induced mouse model,administration of KRT1 antibody mitigated colonic injury,increased colon length,alleviated weight loss,and suppressed inflammatory cytokines such as interleukin(IL)-1,IL-6,tumor necrosis factor-α.It also facilitated repair of the intestinal barrier,reducing DSS-induced injury.CONCLUSION KRT1 inhibits BK expression,suppresses inflammatory cytokines,and enhances markers of intestinal barrier function,thus ameliorating colonic damage and maintaining barrier integrity.KRT1 is a viable therapeutic target for UC.

Mesalazine alleviated the symptoms of spontaneous colitis in interleukin-10 knockout mice by regulating the STAT3/NF-κB signaling pathway

BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa B(NF-κB)signaling pathway,and exacerbate the inflammatory response,thus participating in the pathogenesis of ulcerative colitis(UC).Mesalazine is a commonly used drug in the clinical treatment of UC.However,further studies are needed to determine whether mesalazine regulates the ER stress of intestinal epithelial cells,downregulates the STAT3/NF-κB pathway to play a role in the treatment of UC.AIM To study the therapeutic effects of mesalazine on spontaneous colitis in interleukin-10(IL-10)-/-mice.METHODS The 24-week-old IL-10-/-mice with spontaneous colitis were divided into the model group and the 5-amino salicylic acid group.Littermates of wild-type mice of the same age group served as the control.There were eight mice in each group,four males and four females.The severity of symptoms of spontaneous colitis in IL-10-/-mice was assessed using disease activity index scores.On day 15,the mice were sacrificed.The colon length was measured,and the histopathological changes and ultrastructure of colonic epithelial cells were detected.The protein expressions of STAT3,p-STAT3,NF-κB,IκB,p-IκB,and glucoseregulated protein 78 were identified using Western blotting.The STAT3 and NF-κB mRNA expressions were identified using real-time polymerase chain reaction.The glucose-regulated protein 78 and C/EBP homologous protein expressions in colon sections were detected using immunofluorescence.RESULTS Mesalazine reduced the symptoms of spontaneous colitis in IL-10 knockout mice and the histopathological damage of colonic tissues,and alleviated the ER stress in epithelial cells of colitis mice.Western blotting and quantitative real-time polymerase chain reaction results showed that the STAT3/NF-κB pathway in the colon tissue of model mice was activated,suggesting that this pathway was involved in the pathogenesis of UC and might become a potential therapeutic target.Mesalazine could down-regulate the protein expressions of p-STAT3,NF-κB and p-IκB,and down-regulate the mRNA expression of STAT3 and NF-κB.CONCLUSION Mesalazine may play a protective role in UC by reducing ER stress by regulating the STAT3/NF-κB signaling pathway.

Pre-treatment with IL-1β enhances the efficacy of MSC transplantation in DSS-induced colitis

Mesenchymal stem cells （MSCs） have been used experimentally for treating inflammatory disorders, partly due to their immunosuppressive properties. Although interleukin-1β （IL-1β） is one of the most important inflammatory mediators, growing evidence indicates that IL-1β signaling elicits the immunosuppressive properties of MSCs. However, it remains unclear how IL-1β signaling accomplishes this activity. Here, we focus on the therapeutic efficacy of IL-1β-primed MSCs in the dextran sulfate sodium （DSS）-induced colitis model, in addition to the underlining mechanisms. We first found that IL-1β-primed MSCs, without any observable phenotype change in vitro, significantly attenuated the development of DSS-induced murine colitis. Moreover, IL-1β-primed MSCs modulated the balance of immune cells in the spleen and the mesenteric lymph nodes （MLNs） through elevating cyclooxygenase-2 （COX-2）, IL-6 and IL-8 expression and influencing the polarization of peritoneal macrophages. Importantly, I L- 1β-pri med MSCs possessed an enhanced ability to migrate to the inflammatory site of the gut via upregu lation of chemoki ne receptor type 4 （CXCR4） expression. In summary, IL-1β-primed MSCs have improved efficacy in treating DSS-induced colitis, which at least partly depends on their increased immunosuppressive capacities and enhanced migration ability.

Cortical Inflammation is Increased in a DSS-Induced Colitis Mouse Model

While inflammatory bowel disease(IBD) might be a risk factor in the development of brain dysfunctions,the underlying mechanisms are largely unknown. Here,mice were treated with 5% dextran sodium sulfate(DSS) in drinking water and sacrificed on day 7. The serum level of IL-6 increased, accompanied by elevation of the IL-6 and TNF-a levels in cortical tissue. However, the endotoxin concentration in plasma and brain of mice with DSSinduced colitis showed a rising trend, but with no significant difference. We also found significant activation of microglial cells and reduction in occludin and claudin-5 expression in the brain tissue after DSS-induced colitis.These results suggested that DSS-induced colitis increases systemic inflammation which then results in cortical inflammation via up-regulation of serum cytokines. Here,we provide new information on the impact of colitis on the outcomes of cortical inflammation.

GPP(composition of Ganoderma lucidum polysaccharides and Polyporus umbellatus polysaccharides) protects against DSS-induced murine colitis by enhancing immune function and regulating intestinal flora

Previous study have demonstrated that a compound composed of water-soluable Ganoderma lucidum polysaccharides(GLP)and Polyporus umbellatus polysaccharides(PUP)in a ratio of 3:1 named GPP enhances innate immune function in mice through enhancing the function of macrophage cells and activity of natural killer(NK)cells.Here in our research,we further investigated the effect of GPP on the diversity and composition of intestinal flora,and explored its effect on colitis model mice.The immunoregulatory verification experiments of GPP were conducted in both normal and DSS-induced mice model.Our research showed that GPP increased the diversity of intestinal microorganisms in mice with the extension of administration time.Daily GPP intake attenuated DSS-induced colon injury,protected the splenic lymphocyte proliferation ability,enhanced the serum hemolysin synthesis,and increased peripheral phagocytes and NK cell activity in model mice.Comparisons of the predominant gene pathways of the bacterial microbiota showed that DNA repair and recombination,base mismatch repair pathways was stronger in GPP-treatment group than in control group,indicating the possible molecular mechanisms of immune function regulation.Our study showed that GPP regulated immune function in both health and colitis model,and had a positive effect on maintaining intestinal flora homeostasis.

Stachyose modulates gut microbiota and alleviates DSS-induced ulcerative colitis in mice

Stachyose is a prebiotic that traditionally extracted from plants,such as vegetable.It has been demonstrated to alleviate intestinal inflammation by regulating gut microbiota,but the mechanism has been unclear.This research aims to detect the potential mechanism of stachyose in alleviating the severity of ulcerative colitis(UC).The results indicated that the administration of stachyose could recover the body weight,protect against the colonic tissue damage,reduce the pro-inflammatory cytokines levels,and reverse the histological abnormalities in UC mice.Oral stachyose could restore dextran sulfate sodium(DSS)-induced disturbance in intestinal bacteria.Besides,the metabolome result of serum samples showed that stachyose treatment significantly altered serum metabolites against inflammatory responses in colitis mice.Also,a significant correlation can be found between 23 metabolite biomarkers and 18 differential genera.Our results provided a strong foundation for the future study of the protective role of stachyose in maintaining intestinal homeostasis.

Real-world efficacy and safety of tofacitinib treatment in Asian patients with ulcerative colitis

BACKGROUND Real-world data on tofacitinib(TOF)covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis(UC)are scarce.AIM To investigate the long-term efficacy and safety of TOF treatment for UC,including clinical issues.METHODS We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease center.All consecutive UC patients who received TOF between May 2018 and February 2020 were enrolled.Patients were followed up until August 2020.The primary outcome was the clinical response rate at week 8.Secondary outcomes included clinical remission at week 8,cumulative persistence rate of TOF administration,colectomy-free survival,relapse after tapering of TOF and predictors of clinical response at week 8 and week 48.RESULTS The clinical response and remission rates were 66.3%and 50.5%at week 8,and 47.1%and 43.5%at week 48,respectively.The overall cumulative clinical remission rate was 61.7%at week 48 and history of anti-tumor necrosis factor-alpha(TNF-α)agents use had no influence(P=0.25).The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8(30.9%vs 88.1%;P<0.001).Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8(odds ratio:0.61,95%confidence interval:0.45-0.82,P=0.001).Relapse occurred in 45.7%of patients after TOF tapering,and 85.7%of patients responded within 4 wk after re-increase.All 6 patients with herpes zoster(HZ)developed the infection after achieving remission by TOF.CONCLUSION TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-αagents.Most relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off TOF.Special attention is needed for tapering and HZ.

Emerging role of exosomes in ulcerative colitis: Targeting NOD-like receptor family pyrin domain containing 3 inflammasome

Ulcerative colitis(UC)is a chronic recurrent inflammatory bowel disease.Despite ongoing advances in our understanding of UC,its pathogenesis is yet unelu-cidated,underscoring the urgent need for novel treatment strategies for patients with UC.Exosomes are nanoscale membrane particles that mediate intercellular communication by carrying various bioactive molecules,such as proteins,RNAs,DNA,and metabolites.The NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome is a cytosolic tripartite protein complex whose activation induces the maturation and secretion of proinflammatory cytokines interleukin-1β(IL-1β)and IL-18,triggering the inflammatory response to a pathogenic agent or injury.Growing evidence suggests that exosomes are new modulators of the NLRP3 inflammasome,with vital roles in the pathological process of UC.Here,recent evidence is reviewed on the role of exosomes and NLRP3 inflammasome in UC.First,the dual role of exosomes on NLRP3 inflammasome and the effect of NLRP3 inflammasome on exosome secretion are summarized.Finally,an outlook on the directions of exosome-NLRP3 inflammasome crosstalk research in the context of UC is proposed and areas of further research on this topic are high-lighted.