scholarly journals Lactobacillus reuteri Ameliorates Intestinal Inflammation and Modulates Gut Microbiota and Metabolic Disorders in Dextran Sulfate Sodium-Induced Colitis in Mice

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2298
Author(s):  
Gang Wang ◽  
Shuo Huang ◽  
Shuang Cai ◽  
Haitao Yu ◽  
Yuming Wang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Metabolic Disorders ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Lactobacillus Reuteri ◽  
Intestinal Inflammation ◽  
Intestinal Bacteria ◽  
Ht 29

Lactobacillus reuteri, a commensal intestinal bacteria, has various health benefits including the regulation of immunity and intestinal microbiota. We examined whether L. reuteri I5007 could protect mice against colitis in ameliorating inflammation, modulating microbiota, and metabolic composition. In vitro, HT-29 cells were cultured with L. reuteri I5007 or lipopolysaccharide treatment under three different conditions, i.e., pre-, co- (simultaneous), and posttreatment. Pretreatment with L. reuteri I5007 effectively relieves inflammation in HT-29 cells challenged with lipopolysaccharide. In vivo, mice were given L. reuteri I5007 by gavage throughout the study, starting one week prior to dextran sulfate sodium (DSS) treatment for one week followed by two days without DSS. L. reuteri I5007 improved DSS-induced colitis, which was confirmed by reduced weight loss, colon length shortening, and histopathological damage, restored the mucus layer, as well as reduced pro-inflammatory cytokines levels. Analysis of 16S rDNA sequences and metabolome demonstrates that L. reuteri I5007 significantly alters colonic microbiota and metabolic structural and functional composition. Overall, the results demonstrate that L. reuteri I5007 pretreatment could effectively alleviate intestinal inflammation by regulating immune responses and altering the composition of gut microbiota structure and function, as well as improving metabolic disorders in mice with colitis.

scholarly journals 6,7,4′-Trihydroxyflavanone Protects against Dextran Sulfate Sodium-Induced Colitis by Regulating the Activity of T Cells and Colon Cells In Vivo

2021 ◽  
Vol 22 (4) ◽  
pp. 2083
Author(s):  
Hyun-Su Lee ◽  
Gil-Saeng Jeong
Keyword(s):  
T Cells ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Cell Activity ◽  
Bioactive Molecules ◽  
Colon Cells ◽  
Colon Cell ◽  
Ht 29 ◽  
Colitis Model

Colitis is a multifactorial disorder that mostly occurs in the gastrointestinal tract. Despite improvements in mucosal inflammation research, little is known regarding the small bioactive molecules that are beneficial for regulating T cells and colon cell activity. 6,7,4′-trihydroxyflavanone (THF) is a flavanone that possesses anti-osteoclastogenesis activity and exerts protective effects against methamphetamine-induced immunotoxicity. Whether THF mitigates intestinal inflammation by regulating T cells and colon cell activity remains unknown. In the present study, Jurkat and HT-29 cells were used for in vitro experiments, and dextran sulfate sodium (DSS)-induced colitis model in mice was used for in vivo experiment. We observed that THF did not have a negative effect on the viability of Jurkat and HT-29 cells. Quantitative PCR and Western blot analysis revealed that THF regulates the activity of Jurkat cells and HT-29 cells via the NFκB and MAPK pathways under stimulated conditions. In the DSS-induced colitis model, oral administration of THF attenuated the manifestations of DSS-induced colitis, including a reduction in body weight, shrinkage of the colon, and enhanced expression of pro-inflammatory cytokines in the colon and mesenteric lymph nodes. These data suggest that THF alleviates DSS-induced colitis by modulating the activity of T cells and colon cells in vivo.

Desmethylbellidifolin Attenuates Dextran Sulfate Sodium-Induced Colitis: Impact on Intestinal Barrier, Intestinal Inflammation and Gut Microbiota

Planta Medica ◽  
2021 ◽  
Author(s):  
Jiaqi Wu ◽  
Yuzheng Wu ◽  
Yue Chen ◽  
Mengyang Liu ◽  
Haiyang Yu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Intestinal Inflammation ◽  
Activity Index ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Function Evaluation ◽  
Biological Drugs

AbstractUlcerative colitis has been recognized as a chronic inflammatory disease predominantly disturbing the colon and rectum. Clinically, the aminosalicylates, steroids, immunosuppressants, and biological drugs are generally used for the treatment of ulcerative colitis at different stages of disease progression. However, the therapeutic efficacy of these drugs does not satisfy the patients due to the frequent drug resistance. Herein, we reported the anti-ulcerative colitis activity of desmethylbellidifolin, a xanthone isolated from Gentianella acuta, in dextran sulfate sodium-induced colitis in mice. C57BL/6 mice were treated with 2% dextran sulfate sodium in drinking water to induce acute colitis. Desmethylbellidifolin or balsalazide sodium was orally administrated once a day. Biological samples were collected for immunohistological analysis, intestinal barrier function evaluation, cytokine measurement, and gut microbiota analysis. The results revealed that desmethylbellidifolin alleviated colon shortening and body weight loss in dextran sulfate sodium-induced mice. The disease activity index was also lowered by desmethylbellidifolin after 9 days of treatment. Furthermore, desmethylbellidifolin remarkably ameliorated colonic inflammation through suppressing the expression of interleukin-6 and tumor necrosis factor-α. The intestinal epithelial barrier was strengthened by desmethylbellidifolin through increasing levels of occludin, ZO-1, and claudins. In addition, desmethylbellidifolin modulated the gut dysbiosis induced by dextran sulfate sodium. These findings suggested that desmethylbellidifolin effectively improved experimental ulcerative colitis, at least partly, through maintaining intestinal barrier integrity, inhibiting proinflammatory cytokines, and modulating dysregulated gut microbiota.

7 LACTOBACILLUS REUTERI SUPPRESSES PRO-INFLAMMATORY DRIVEN REACTIVE OXYGEN SPECIES IN VITRO IN HUMAN INTESTINAL EPITHELIAL CELLS AND IN VIVO IN A TNBS COLITIS MOUSE MODEL

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S41-S41 ◽  
Author(s):  
Wenly Ruan ◽  
Melinda Engevik ◽  
Alexandra Chang-Graham ◽  
Joseph Hyser ◽  
James Versalovic
Keyword(s):  
Reactive Oxygen Species ◽  
Epithelial Cells ◽  
Lactobacillus Reuteri ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial Cells ◽  
Oxygen Species ◽  
Intestinal Epithelial ◽  
Colitis Model

Abstract Background Reactive oxygen species (ROS) play a role in maintaining intestinal epithelial homeostasis and are normally kept at low levels via antioxidant compounds. Dysregulation of ROS can lead to intestinal inflammation and contribute to inflammatory bowel disease (IBD). Select gut microbes possess the enzymatic machinery to produce antioxidants whereas others can dysregulate levels of ROS. Our model microbe, Lactobacillus reuteri (ATCC PTA 6475), has been demonstrated to reduce intestinal inflammation in mice models. It contains the genes encoding two distinct GshA-like glutamylcysteine ligases. We hypothesize that L. reuteri can secrete γ-glutamylcysteine to suppress ROS, minimize NFκB activation and regulate secretion of e pithelial cytokines. Methods & Results Conditioned media from L. reuteri was analyzed via mass spectrometry to confirm the presence of γ-glutamylcysteine. All cysteine containing products including γ-glutamylcysteine were fluorescently tagged in the conditioned media and then incubated with HT29 cell monolayers as well as human jejunal enteroid (HJE) monolayers. γ-glutamylcysteine was demonstrated to enter intestinal epithelial cells based on microscopy. Next, a Thioltracker assay was used to show increased intracellular glutathione levels by L. reuteri secreted γ-glutamylcysteine. HT29 cells and HJEs were then treated with IL-1β or hydrogen peroxide, and L. reuteri metabolites as well as γ-glutamylcysteine significantly suppressed pro-inflammatory cytokine driven ROS and IL-8 production. L. reuteri secreted products also reduced activity of NFκB as determined by a luciferase reporter assay. γ-glutamylcysteine deficient mutants were generated by targeted mutagenesis of GshA genes, and these mutant L. reuteri strains had a diminished ability to suppress IL-8 production and ROS. To further test the role of L. reuteri secreted γ-glutamylcysteine in vivo, a 2,4,6-Trinitrobenzenesulfonic acid (TNBS)- induced mouse colitis model was used. Adolescent mice were orogavaged with PBS, L. reuteri, L. reuteri GshA2 mutant, or γ-glutamylcysteine for a week after which TNBS was rectally administered to induce colitis. We demonstrate that L. reuteri and γ-glutamylcysteine can suppress histologic inflammation compared to PBS control and L. reuteri GshA2 mutant groups. Conclusions Together these data indicate that L. reuteri secretes γ-glutamylcysteine which can enter the intestinal epithelial cells and modulate epithelial cytokine production. It acts via suppression of ROS and NFκB which then decreases IL-8 production. We are able to demonstrate this in vitro in both HT 29 cells and HJEs. We now also demonstrate this in vivo in a mouse colitis model. These experiments highlight a prominent role for ROS intermediates in microbiome-mammalian cell signaling processes involved in immune responses and intestinal inflammation.

scholarly journals Schisandrin A protects intestinal epithelial cells from deoxynivalenol-induced cytotoxicity, oxidative damage and inflammation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Murphy L. Y. Wan ◽  
Paul C. Turner ◽  
Vanessa A. Co ◽  
M. F. Wang ◽  
Khaled M. A. Amiri ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intestinal Inflammation ◽  
Health Concern ◽  
Heme Oxygenase 1 ◽  
Antioxidant Enzyme Activities ◽  
Transferase Activity ◽  
Nuclear Factor ◽  
Ht 29

AbstractExtensive research has revealed the association of continued oxidative stress with chronic inflammation, which could subsequently affect many different chronic diseases. The mycotoxin deoxynivalenol (DON) frequently contaminates cereals crops worldwide, and are a public health concern since DON ingestion may result in persistent intestinal inflammation. There has also been considerable attention over the potential of DON to provoke oxidative stress. In this study, the cytoprotective effect of Schisandrin A (Sch A), one of the most abundant active dibenzocyclooctadiene lignans in the fruit of Schisandra chinensis (Turcz.) Baill (also known as Chinese magnolia-vine), was investigated in HT-29 cells against DON-induced cytotoxicity, oxidative stress and inflammation. Sch A appeared to protect against DON-induced cytotoxicity in HT-29 cells, and significantly lessened the DON-stimulated intracellular reactive oxygen species and nitrogen oxidative species production. Furthermore, Sch A lowered DON-induced catalase, superoxide dismutase and glutathione peroxidase antioxidant enzyme activities but maintains glutathione S transferase activity and glutathione levels. Mechanistic studies suggest that Sch A reduced DON-induced oxidative stress by down-regulating heme oxygenase-1 expression via nuclear factor (erythroid-derived 2)-like 2 signalling pathway. In addition, Sch A decreased the DON-induced cyclooxygenase-2 expression and prostaglandin E2 production and pro-inflammatory cytokine interleukin 8 expression and secretion. This may be mediated by preventing DON-induced translocation of nuclear factor-κB, as well as activation of mitogen-activated protein kinases pathways. In the light of these findings, we concluded that Sch A exerted a cytoprotective role in DON-induced toxicity in vitro, and it would be valuable to examine in vivo effects.

Effects of flavonoids on intestinal inflammation, barrier integrity and changes in gut microbiota during diet-induced obesity

2016 ◽  
Vol 29 (2) ◽  
pp. 234-248 ◽  
Author(s):  
Katherine Gil-Cardoso ◽  
Iris Ginés ◽  
Montserrat Pinent ◽  
Anna Ardévol ◽  
Mayte Blay ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Mucosal Barrier ◽  
Low Grade ◽  
Protective Effects ◽  
Barrier Integrity ◽  
Diet Induced Obesity

AbstractDiet-induced obesity is associated with low-grade inflammation, which, in most cases, leads to the development of metabolic disorders, primarily insulin resistance and type 2 diabetes. Although prior studies have implicated the adipose tissue as being primarily responsible for obesity-associated inflammation, the latest discoveries have correlated impairments in intestinal immune homeostasis and the mucosal barrier with increased activation of the inflammatory pathways and the development of insulin resistance. Therefore, it is essential to define the mechanisms underlying the obesity-associated gut alterations to develop therapies to prevent and treat obesity and its associated diseases. Flavonoids appear to be promising candidates among the natural preventive treatments that have been identified to date. They have been shown to protect against several diseases, including CVD and various cancers. Furthermore, they have clear anti-inflammatory properties, which have primarily been evaluated in non-intestinal models. At present, a growing body of evidence suggests that flavonoids could exert a protective role against obesity-associated pathologies by modulating inflammatory-related cellular events in the intestine and/or the composition of the microbiota populations. The present paper will review the literature to date that has described the protective effects of flavonoids on intestinal inflammation, barrier integrity and gut microbiota in studies conducted using in vivo and in vitro models.

scholarly journals Cinacalcet Targets the Neurokinin-1 Receptor and Inhibits PKCδ/ERK/P65 Signaling to Alleviate Dextran Sulfate Sodium-Induced Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuehong Chen ◽  
Huan Liu ◽  
Qiuping Zhang ◽  
Yubin Luo ◽  
Liang Wu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Structural Integrity ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Therapeutic Effects ◽  
Neurokinin 1 Receptor ◽  
Neurokinin 1

Objective: Inflammatory bowel disease is an immune-mediated chronic inflammatory disease of the gastrointestinal tract for which curative drugs are currently not available. This study was performed to assess the therapeutic effects of cinacalcet on dextran sulfate sodium (DSS)-induced colitis.Methods: Primary macrophages obtained from bone marrow and the macrophage cell line RAW264.7 were used to examine the inhibitory effect of cinacalcet on cytokine production, the PKCδ/ERK/P65 signaling pathway, and NF-κB P65 translocation. Colitis was induced using DSS to assess the treatment effect of cinacalcet. Bioinformatics approaches were adopted to predict potential targets of cinacalcet, and a drug affinity responsive target stability (DARTs) assay was performed to confirm binding between cinacalcet and potential target.Results:In vivo analysis showed that cinacalcet reduced the disease activity score, prevented shortening of the colon, diminished inflammatory cell infiltration, and protected the structural integrity of the intestinal wall. Cinacalcet also reduced production of the inflammatory cytokines TNFα, IL-1β, and IL-6 in the colon and sera of mice with DSS-induced colitis. In vitro studies revealed that cinacalcet suppressed the translocation of P65 and inhibited production of the inflammatory cytokines IL-1β and IL-6. Mechanistic studies revealed that the target of cinacalcet was neurokinin-1 receptor (NK1R) and their binding was confirmed by a DARTs assay. Furthermore, the inhibition of NK-κB P65 activation was found to occur via the suppression of PKCδ/ERK/P65 signaling mediated by cinacalcet.Conclusion: Cinacalcet inhibits the activation of NF-κB and reduces the production of inflammatory cytokines by suppressing the PKCδ/ERK/P65 signaling pathway via targeting NK1R, suggesting that it can be used to treat inflammatory diseases, particularly colitis.

scholarly journals Tanshinone IIA Protects against Dextran Sulfate Sodium- (DSS-) Induced Colitis in Mice by Modulation of Neutrophil Infiltration and Activation

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaowei Liu ◽  
Haiyue He ◽  
Tingting Huang ◽  
Zhen Lei ◽  
Fuquan Liu ◽  
...  
Keyword(s):  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Intestinal Inflammation ◽  
Therapeutic Potential ◽  
Activity Index ◽  
Critical Role ◽  
Neutrophil Migration ◽  
Neutrophil Infiltration ◽  
Tanshinone Iia

Neutrophils play a critical role in the initiation and maintenance of intestinal inflammation. However, conventional neutrophil-targeted therapies can impair normal host defense. Tanshinone IIA has been recently revealed to act directly on neutrophils. Hence, we aimed at investigating whether Tanshinone IIA can protect against experimental colitis through modulation of neutrophils. We induced colitis in C57BL/6 mice by giving 3% dextran sulfate sodium (DSS) orally, and meanwhile, we treated mice daily with Tanshinone IIA intraperitoneally. The severity of colitis was evaluated by calculating disease activity index (DAI) and histological parameters. Neutrophil infiltration and activation in the colons of mice were measured. Moreover, whether Tanshinone IIA has direct effects on neutrophil migration and activation was determined in vitro. Our data showed that Tanshinone IIA significantly ameliorated the severity of DSS-induced colitis in mice, evidenced by the reduced DAI and improved colonic inflammation. In addition, Tanshinone IIA decreased neutrophil infiltration of intestinal mucosa and activation and reduced colonic inflammatory cytokines in DSS-treated mice. Furthermore, Tanshinone IIA was demonstrated to significantly suppress neutrophil migration and activation. These results provide compelling evidence that Tanshinone IIA has a therapeutic potential for alleviating inflammatory colitis in mice, which is possibly mediated by the immunomodulation of neutrophils.

scholarly journals Gut microbiota-mediated lysophosphatidylcholine generation promotes colitis in intestinal epithelium-specific Fut2 deficiency

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Xuelian Tang ◽  
Weijun Wang ◽  
Gaichao Hong ◽  
Caihan Duan ◽  
Siran Zhu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intestinal Epithelium ◽  
Intestinal Inflammation ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Epithelial Barrier ◽  
16S Rrna Analysis ◽  
New Strategy

Abstract Background and aims Previous study disclosed Fucosyltransferase 2 (Fut2) gene as a IBD risk locus. This study aimed to explore the mechanism of Fut2 in IBD susceptibility and to propose a new strategy for the treatment of IBD. Methods Intestinal epithelium-specific Fut2 knockout (Fut2△IEC) mice was used. Colitis was induced by dextran sulfate sodium (DSS). The composition and diversity of gut microbiota were assessed via 16S rRNA analysis and the metabolomic findings was obtained from mice feces via metabolite profiling. The fecal microbiota transplantation (FMT) experiment was performed to confirm the association of gut microbiota and LPC. WT mice were treated with Lysophosphatidylcholine (LPC) to verify its impact on colitis. Results The expression of Fut2 and α-1,2-fucosylation in colonic tissues were decreased in patients with UC (UC vs. control, P = 0.036) and CD (CD vs. control, P = 0.031). When treated with DSS, in comparison to WT mice, more severe intestinal inflammation and destructive barrier functions in Fut2△IEC mice was noted. Lower gut microbiota diversity was observed in Fut2△IEC mice compared with WT mice (p < 0.001). When exposed to DSS, gut bacterial diversity and composition altered obviously in Fut2△IEC mice and the fecal concentration of LPC was increased. FMT experiment revealed that mice received the fecal microbiota from Fut2△IEC mice exhibited more severe colitis and higher fecal LPC concentration. Correlation analysis showed that the concentration of LPC was positively correlated with four bacteria—Escherichia, Bilophila, Enterorhabdus and Gordonibacter. Furthermore, LPC was proved to promote the release of pro-inflammatory cytokines and damage epithelial barrier in vitro and in vivo. Conclusion Fut2 and α-1,2-fucosylation in colon were decreased not only in CD but also in UC patients. Gut microbiota in Fut2△IEC mice is altered structurally and functionally, promoting generation of LPC which was proved to promote inflammation and damage epithelial barrier.

Energy Drink Administration Ameliorates Intestinal Epithelial Barrier Defects and Reduces Acute DSS Colitis

2021 ◽  
Author(s):  
Roberto Manzini ◽  
Marlene Schwarzfischer ◽  
Anna Bircher ◽  
Anna Niechcial ◽  
Stephan R Vavricka ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Intestinal Inflammation ◽  
Energy Drink ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Energy Drink Consumption ◽  
Ht 29 ◽  
Pro Inflammatory Cytokines

Abstract Background The rise in the prevalence of inflammatory bowel diseases in the past decades coincides with changes in nutritional habits, such as adaptation of a Western diet. However, it is largely unknown how certain nutritional habits, such as energy drink consumption, affect intestinal inflammation. Here, we assessed the effect of energy drink supplementation on the development of intestinal inflammation in vitro and in vivo. Methods HT-29 and T84 intestinal epithelial cells and THP-1 monocytic cells were treated with IFNγ in presence or absence of different concentrations of an energy drink. Colitis was induced in C57BL/6 mice by addition of dextran sodium sulfate (DSS) to drinking water with or without supplementation of the energy drink. Results Energy drink supplementation caused a dose-dependent decrease in IFNγ-induced epithelial barrier permeability, which was accompanied by upregulation of the pore-forming protein claudin-2. Administration of the energy drink reduced secretion of the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-α from HT-29, T84, and THP-1 cells. In vivo, energy drink administration reduced clinical symptoms of DSS-induced colitis and epithelial barrier permeability. Endoscopic and histologic colitis scores and expression of pro-inflammatory cytokines were significantly reduced by energy drink co-administration. Conclusion Energy drink consumption seems to exert an unexpected anti-inflammatory effect in vitro and in vivo in our experimental setting. However, our experimental approach focuses on intestinal inflammation and neglects additional effects of energy drink consumption on the body (eg, on metabolism or sleep). Therefore, the translation of our findings into the human situation must be taken with caution.

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