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1.
J Sci Food Agric ; 102(1): 434-444, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34143895

RESUMO

BACKGROUND: The incidence of inflammatory bowel disease (IBD) continues to increase worldwide. Multiple factors, including diet, loss of the intestinal barrier function, and imbalance of the immune system can cause IBD. A balanced diet is important for maintaining a healthy bowel and preventing IBD from occurring. The effects of probiotic Lactobacillus gasseri-fermented Maillard reaction products (MRPs) prepared by reacting whey protein with galactose on anti-inflammation and intestinal homeostasis were investigated in this study, which compared MPRs and probiotics separately. RESULTS: In an animal colitis model induced by 2% dextran sulfate sodium (DSS), FWG administration alleviated colon length loss and maintained intestinal immune system homeostasis as reflected by down-regulated interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α output, and metallopeptidase-9, and epithelial barrier balance as reflected by up-regulated occludin, E-cadherin, and zonula occludens-1 production in the colon. Furthermore, the expression of splenic cytokines such as IL-6, TNF-α, and IL-10 was up-regulated in the FWG-treated mice in a comparable amount to the control group to ensure the balance of immune responses. CONCLUSION: This study showed that the use of FWG protects the intestines from colitis caused by DSS and maintains immune balance. FWG increased antioxidant enzyme activity, increased intestinal permeability, and regulated the balance of pro- and anti-inflammatory cytokines in the intestines and spleen. Continued intake of FWG can alleviate IBD symptoms through the preservation of mucosal immune responses, epithelial junction and homeostasis through the regulated splenic cytokines. © 2021 Society of Chemical Industry.


Assuntos
Colite/tratamento farmacológico , Produtos Finais de Glicação Avançada/administração & dosagem , Lactobacillus gasseri/metabolismo , Probióticos/administração & dosagem , Animais , Anti-Inflamatórios/administração & dosagem , Colite/induzido quimicamente , Colite/imunologia , Colite/fisiopatologia , Colo/efeitos dos fármacos , Colo/imunologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Galactose/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Homeostase/efeitos dos fármacos , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Junções Íntimas/genética , Junções Íntimas/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Proteínas do Soro do Leite/metabolismo
2.
Environ Pollut ; 292(Pt B): 118477, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34763016

RESUMO

As a common fungicide, tebuconazole are ubiquitous in the natural environment and poses many potential risks. In this study, we examined the effects of exposure to tebuconazole on colitis in mice and explored its underlying mechanism. Specifically, exposure to tebuconazole could cause structural damage and inflammatory cell infiltration in colon tissue, activate the expression of inflammation-related genes, disrupt the expression of barrier function-related genes, and induce the colonic inflammation in mice. Similarly, exposure to tebuconazole could also exacerbate DSS-induced colitis in mice. In addition, we found that tebuconazole also could change the composition of the gut microbiota. In particular, tebuconazole significantly increases the relative abundance of Akkermansia of mice. Moreover, tebuconazole resulted in metabolic profiles disorders of the serum, leading to significant changes in the relative contents of metabolites involving glycolipid metabolism and amino acid metabolism. Particularly, the results of the gut microbiota transplantation experiment showed that exposure to tebuconazole could induced colonic inflammation in mice in a gut microbiota-dependent manner. Taken together, these results indicated that tebuconazole could induce colitis in mice via regulating gut microbiota. Our findings strongly support the concept that the gut microbiota is a key trigger of inflammatory bowel disease caused by pesticide intake.


Assuntos
Colite , Fungicidas Industriais , Microbioma Gastrointestinal , Animais , Colite/induzido quimicamente , Sulfato de Dextrana , Modelos Animais de Doenças , Fungicidas Industriais/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Triazóis
3.
Environ Pollut ; 292(Pt B): 118351, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34637830

RESUMO

Particulate matter exposure and related chemical changes in drinking water have been associated with health problems and inflammatory disorders. This study aimed to examine the effect of orally administered ash-water dilution on the gut of mice under normal and inflammatory conditions. Balb/c mice received ash-released soluble and dust-suspended components in the drinking water for 14 days. On day 7, animals were intrarectally instilled with TNBS in ethanol or flagellin from Salmonella typhimurium in PBS. At sacrifice, colon segments were collected and histologic damage, mRNA expression and cytokine levels in tissue were evaluated. In addition, these parameters were also evaluated in IL-10 null mice. We found that mice that received 5% w. fine-ash dilution in the drinking water worsened colitis signs. Weight loss, shortening of the colon, tissue edema with mucosa and submucosa cell infiltration and production of pro-inflammatory cytokines and chemokines were enhanced compared to control mice. A more pronounced inflammation was observed in IL-10 null mice. In addition, markers of NLRP3-dependent inflammasome activation were found in animals exposed to ash. In conclusion, ingestion of contaminated water with dust-suspended particulate matter enhanced the inflammatory response in the gut, probably due to alteration of the gut barrier and promoting an intense contact with the luminal content. This study critically appraises the response for fine particulate matter in uncommon illnesses reported for volcanic ash pollution. We suggest actions to enable better prediction and assessment the health impacts of volcanic eruptions.


Assuntos
Colite , Erupções Vulcânicas , Animais , Colite/induzido quimicamente , Inflamação/induzido quimicamente , Camundongos , Material Particulado/toxicidade
4.
J Agric Food Chem ; 69(44): 13034-13044, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34723501

RESUMO

Dietary ethanolamine plasmalogen (PlsEtn) has been reported to have several health benefits; however, its functional role during colon pathophysiology remains elusive. The present study investigated the anticolitis effect of dietary ethanolamine glycerophospholipids (EtnGpls) with high PlsEtn from ascidian muscle (86.2 mol %) and low PlsEtn from porcine liver (7.7 mol %) in dextran sulfate sodium (DSS)-induced colitis in mice. Dietary EtnGpls lowered myeloperoxidase activity, thiobarbituric acid-reactive substances, proinflammatory cytokines and proapoptosis-related protein levels in colon mucosa after 16 days of DSS treatment, with ascidian muscle (0.1% EtnGpl in diet) showing higher suppression than porcine liver (0.1% EtnGpl in diet). Moreover, dietary EtnGpls suppressed DSS symptoms after 38 days of DSS treatment as evidenced by increased body weight, colon length, and ameliorated colon mucosa integrity. Additionally, dietary EtnGpls elevated short-chain fatty acid production in DSS-treated mice. Altogether, these results indicate the potential of utilizing diets with abundant PlsEtn for the prevention of colon inflammation-related disorders.


Assuntos
Colite , Animais , Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/genética , Colo/metabolismo , Sulfato de Dextrana/metabolismo , Dieta , Modelos Animais de Doenças , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Plasmalogênios , Suínos , Compostos de Vinila
5.
Phytomedicine ; 93: 153804, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34735907

RESUMO

BACKGROUND: Mosla chinensis Maxim. cv. Jiangxiangru (JXR), a traditional Chinese medicine, commonly used for the therapy of cold, fever, diarrhea, digestive disorders, and other diseases. Inflammatory bowel disease (IBD) is a chronic disorder of the human gastrointestinal tract. Research about the effect of JXR on IBD and the active ingredient composition of JXR remains deficiency. PURPOSE: This study aims to determine the phytochemical composition and the anti-inflammatory property of JXR, as well as the possible anti-inflammatory mechanisms. METHODS: The bioactive profile of JXR extracts was determined by UPLC-LTQ-Orbitrap-MS. A DSS induced colitis mouse model was applied to explore the anti-inflammatory activity of JXR. The body weight, colon length and histopathological status of colon tissue were evaluated. The content of inflammatory mediators (nitric oxide (NO), prostaglandin E2 (PGE2)) and cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß)), corresponding mRNA and protein expression levels were analyzed. Oxidation pressure and gut microbial composition were also explored. RESULTS: Totally 63 constitutes were identified from JXR, among them, phenolic acids and flavonoids comprised a large part, and rosmarinic acid (RA) was the main compound. The results of DSS-induced colitis mice model indicated that JXR effectively ameliorated inflammation, restore the redox balance in the gut. JXR treatment significantly reduced the production of reactive oxygen species (ROS), increased the activity of antioxidative enzyme, suppressed the secretion of inflammatory mediators (NO, PGE2) and cytokines (TNF-α, IL-6, IL-1ß). JXR also restrained the activation of mitogen-activated protein kinases (MAPKs) signaling pathway. Furthermore, JXR could restore the microbial diversity by suppressing Bacteroidaceae, increasing Bifidobacteriales and Melainabacteria in DSS colitis mouse model. CONCLUSIONS: This study demonstrated that JXR composed with various bioactive compounds, effectively ameliorated colitis, restored the redox balance and regulated gut microbiota. Results from the present study provide an insight of therapeutic potential of JXR in IBD based on its anti-inflammatory and antioxidant properties, also provide a scientific basis for using JXR as a functional ingredient to promote colon health.


Assuntos
Colite , Microbioma Gastrointestinal , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo , Citocinas , Sulfato de Dextrana , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL
6.
BMC Gastroenterol ; 21(1): 361, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34600483

RESUMO

BACKGROUND: Ixekizumab is monoclonal antibody targeted against interleukin-17 (IL-17) and has been approved for use in chronic plaque psoriasis. Despite its efficacy in treating psoriasis, concerns have been raised regarding Ixekizumab's potential to induce and exacerbate inflammatory bowel disease (IBD). CASE PRESENTATION: Here we report the new onset of severe drug-associated colitis with surgical complications in a 45-year-old male patient who was receiving Ixekizumab therapy for chronic plaque psoriasis. Review of the patient's colonic pathology demonstrated acute inflammatory changes with features of Crohn's disease. The patient remained disease-free 9-months following his hospitalization and cessation of Ixekizumab. CONCLUSIONS: This case raises suspicion for an association between Ixekizumab and IBD and calls on clinicians to have heightened awareness of potential risks before prescribing anti-IL-17 agents.


Assuntos
Colite , Doença de Crohn , Fármacos Dermatológicos , Preparações Farmacêuticas , Psoríase , Anticorpos Monoclonais Humanizados , Colite/induzido quimicamente , Colite/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do Tratamento
7.
BMJ Case Rep ; 14(10)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598959

RESUMO

Diversion colitis (DC) that was refractory to standard treatments was successfully treated with infliximab. A 24-year-old man with a transverse colostomy suffered from severe DC. Topical steroids, 5-aminosalicylic acid (5-ASA) enemas and synbiotics were initially effective, and the colostomy was successfully closed with a covering ileostomy to minimise the risk of anastomotic leakage owing to the damaged colon. DC subsequently relapsed in the entire colon and was refractory to the previous protocol and autologous faecal transplantation. Intravenous methylprednisolone and oral 5-ASA were discontinued owing to possible adverse effects. Infliximab with intravenous prednisolone was introduced, and the protocol was so effective in suppressing the acute colitis that total colectomy was avoided. The stoma was subsequently closed, and the patient is currently symptom-free. Infliximab is used for ulcerative colitis but could also be effective against severe DC.


Assuntos
Colite Ulcerativa , Colite , Adulto , Colectomia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/cirurgia , Humanos , Infliximab/uso terapêutico , Masculino , Mesalamina/uso terapêutico , Resultado do Tratamento , Adulto Jovem
8.
FASEB J ; 35(11): e21950, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34613638

RESUMO

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders characterized by relapsing intestinal inflammation, but many details of pathogenesis remain to be fully unraveled. Glucocorticoid (GC)-induced leucine zipper (GILZ) is a mediator of the anti-inflammatory effects of GCs, the most powerful drugs for IBD treatment, but they cause several unwanted side effects. The fusion protein TAT-GILZ has been successfully used in some pre-clinical models of inflammatory and autoimmune diseases. To test the efficacy of TAT-GILZ for treating dextran sulfate sodium (DSS)-induced colitis and explore its impact on the gut microbiome, colitis was induced by DSS in C57BL/6J mice and treated with TAT-GILZ or dexamethasone. Various hallmarks of colitis were analyzed, including disease activity index, gut permeability, and expression of pro-inflammatory cytokines and tight junction proteins. TAT-GILZ treatment showed a therapeutic effect when administered after the onset of colitis. Its efficacy was associated with improved gut permeability, as evidenced by zonula occludens-1 and CD74 upregulation in inflamed colonic tissue. TAT-GILZ also ameliorated the changes in the gut microbiota induced by the DSS, thus potentially providing an optimal environment for colonization of the mucosa surface by beneficial bacteria. Overall, our results demonstrated for the first time that TAT-GILZ treatment proved effective after disease onset allowing restoration of gut permeability, a key pathogenic feature of colitis. Additionally, TAT-GILZ restored gut dysbiosis, thereby contributing to healing mechanisms. Interestingly, we found unprecedented effects of exogenous GILZ that did not overlap with those of GCs.


Assuntos
Colite/induzido quimicamente , Colite/tratamento farmacológico , Sulfato de Dextrana/efeitos adversos , Mucosa Intestinal/metabolismo , Permeabilidade/efeitos dos fármacos , Proteínas Recombinantes de Fusão/administração & dosagem , Fatores de Transcrição/administração & dosagem , Animais , Anti-Inflamatórios/administração & dosagem , Antígenos de Diferenciação de Linfócitos B/metabolismo , Colite/metabolismo , Citocinas/metabolismo , Dexametasona/administração & dosagem , Modelos Animais de Doenças , Antígenos de Histocompatibilidade Classe II/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Transativadores/genética , Fatores de Transcrição/genética , Resultado do Tratamento , Regulação para Cima/efeitos dos fármacos , Proteína da Zônula de Oclusão-1/metabolismo
9.
Nutrients ; 13(10)2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34684516

RESUMO

The metabolic disorder caused by excessive fructose intake was reported extensively and often accompanied by intestinal barrier dysfunction. And the rising dietary fructose was consumed at an early age of human. However, related researches were almost conducted in rodent models, while in the anatomy and physiology of gastrointestinal tract, pig is more similar to human beings than rodents. Hence, weaned piglets were chosen as the model animals in our study to investigate the fructose's impacts on intestinal tight junction, inflammation response and microbiota structure of piglets. Herein, growth performance, inflammatory response, oxidation resistance and ileal and colonic microbiota of piglet were detected after 35-day fructose supplementation. Our results showed decreased tight junction gene expressions in piglets after fructose addition, with no obvious changes in the growth performance, antioxidant resistance and inflammatory response. Moreover, fructose supplementation differently modified the microbiota structures in ileum and colon. In ileum, the proportions of Streptococcus and Faecalibacterium were higher in Fru group (fructose supplementation). In colon, the proportions of Blautia and Clostridium sensu stricto 1 were higher in Fru group. All the results suggested that tight junction dysfunction might be an earlier fructose-induced event than inflammatory response and oxidant stress and that altered microbes in ileum and colon might be the potential candidates to alleviate fructose-induced intestinal permeability alteration.


Assuntos
Colite/induzido quimicamente , Suplementos Nutricionais/efeitos adversos , Frutose/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Animais , Colo/efeitos dos fármacos , Íleo/efeitos dos fármacos , Modelos Animais , Estresse Oxidativo/efeitos dos fármacos , Permeabilidade/efeitos dos fármacos , Suínos , Junções Íntimas/efeitos dos fármacos
10.
J Med Food ; 24(11): 1169-1171, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34704834

RESUMO

The immunomodulatory effects of Lactobacillus rhamnosus HDB1258 were evaluated in mice with colitis induced by Klebsiella oxytoca (KO). L. rhamnosus HDB1258 was cultured in the lava seawater (LS) to improve its probiotic properties. It increased adhesive ability to mucin with mRNA expression levels of chaperone proteins (such as GroEL/ES, DnaKJ, and HtrA). In the in vivo experiments, administration of KO caused an inflammation on the colon with gut dysbiosis. LH group (oral gavage of HDB1258 1.0 × 109 colony forming units/day) showed that inflammatory biomarkers, including IL-1ß, TNF-α, IL-6, and PGE2, were significantly decreased to less than half of the KO group, and Th1 cells were decreased in the spleen, but Treg cells were not affected. In contrast, the expression levels of secretory IgA and IL-10 were significantly increased, and the composition of gut microbiota in the LH group tended to recover similar to normal mice without any effect on the α-diversity. In conclusion, L. rhamnosus HDB1258 cultured in the LS could regulate competitively pathogenic bacteria in imbalanced flora with its improved mucin adhesive ability and was an effective immunomodulatory adjuvant for treating colitis by its regulatory function on intestinal inflammation.


Assuntos
Colite , Microbioma Gastrointestinal , Lactobacillus rhamnosus , Probióticos , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/genética , Citocinas , Camundongos , Água do Mar
11.
J Agric Food Chem ; 69(43): 12753-12762, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34693717

RESUMO

Hesperetin-7-O-glucoside (Hes-7-G) is a naturally occurring flavonoid monoglucoside in Citri Reticulatae Pericarpium and exhibits relatively high biological activities. To explore the anti-inflammatory capacity of dietary Hes-7-G, lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and dextran sodium sulfate (DSS)-induced colitis mice were used here as in vitro and in vivo inflammation models. The results showed that Hes-7-G (5 µM) significantly restored cellular metabolic disorders and inflammation in LPS-stimulated RAW264.7 macrophages. In the in vivo study, dietary Hes-7-G (1 mg/kg body weight) markedly alleviated the inflammatory status in DSS-induced colitis mice, manifested by the recovered colon length from 5.91 ± 0.66 to 6.45 ± 0.17 cm, histopathological changes, and mRNA levels of colonic inflammatory factors including Tnf-α and Il-22. Furthermore, dietary Hes-7-G not only profoundly regulated the gut microbiota composition including phyla Bacteroidetes, Cyanobacteria, Desulfobacterota, and Deferribacteres and genus Enterorhabdus, Prevotellaceae, Gastranaerophilales, Enterococcus, Intestinimonas, Ruminococcaceae, and Eubacterium in the cecal contents but also especially adjusted the co-metabolites such as short chain fatty acids and indole metabolites (indole-3-propionic, indole acetic acid), which were markedly altered by DSS treatment in mice. These findings demonstrated that Hes-7-G has strong anti-inflammatory activity in vitro and in vivo and potential preventive or therapeutic effects for chronic inflammation diseases.


Assuntos
Colite , Animais , Anti-Inflamatórios/uso terapêutico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo , Citocinas , Sulfato de Dextrana , Modelos Animais de Doenças , Glucosídeos/uso terapêutico , Hesperidina , Camundongos , Camundongos Endogâmicos C57BL
12.
Nat Commun ; 12(1): 5954, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642329

RESUMO

Leptomeningeal disease (LMD) is a common complication from solid tumor malignancies with a poor prognosis and limited treatment options. We present a single arm Phase II study of 18 patients with LMD receiving combined ipilimumab and nivolumab until progression or unacceptable toxicity (NCT02939300). The primary end point is overall survival at 3 months (OS3). Secondary end points include toxicity, cumulative time-to-progression at 3 months, and progression-free survival. A Simon two-stage design is used to compare a null hypothesis OS3 of 18% against an alternative of 44%. Median follow up based on patients still alive is 8.0 months (range: 0.5 to 15.9 months). The study has met its primary endpoint as 8 of 18 (OS3 0.44; 90% CI: 0.24 to 0.66) patients are alive at three months. One third of patients have experienced one (or more) grade-3 or higher adverse events. Two patients have discontinued protocol treatment due to unacceptable toxicity (hepatitis and colitis, respectively). The most frequent adverse events include fatigue (N = 7), nausea (N = 6), fever (N = 6), anorexia (N = 6) and rash (N = 6). Combined ipilimumab and nivolumab has an acceptable safety profile and demonstrates promising activity in LMD patients. Larger, multicenter clinical trials are needed to validate these results.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas/tratamento farmacológico , Ipilimumab/administração & dosagem , Carcinomatose Meníngea/tratamento farmacológico , Neoplasias Meníngeas/tratamento farmacológico , Nivolumabe/administração & dosagem , Adulto , Idoso , Anorexia/induzido quimicamente , Anorexia/mortalidade , Anorexia/patologia , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Colite/induzido quimicamente , Colite/mortalidade , Colite/patologia , Exantema/induzido quimicamente , Exantema/mortalidade , Exantema/patologia , Fadiga/induzido quimicamente , Fadiga/mortalidade , Fadiga/patologia , Feminino , Febre/induzido quimicamente , Febre/mortalidade , Febre/patologia , Hepatite/etiologia , Hepatite/mortalidade , Hepatite/patologia , Humanos , Ipilimumab/efeitos adversos , Masculino , Carcinomatose Meníngea/mortalidade , Carcinomatose Meníngea/patologia , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/patologia , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/mortalidade , Náusea/patologia , Nivolumabe/efeitos adversos , Análise de Sobrevida
13.
Nutrients ; 13(10)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34684567

RESUMO

Commonly used synthetic dietary emulsifiers, including carboxymethylcellulose (CMC) and polysorbate-80 (P80), promote intestinal inflammation. We compared abilities of CMC vs. P80 to potentiate colitis and impact human microbiota in an inflammatory environment using a novel colitis model of ex-germ-free (GF) IL10-/- mice colonized by pooled fecal transplant from three patients with active inflammatory bowel diseases. After three days, mice received 1% CMC or P80 in drinking water or water alone for four weeks. Inflammation was quantified by serial fecal lipocalin 2 (Lcn-2) and after four weeks by blinded colonic histologic scores and colonic inflammatory cytokine gene expression. Microbiota profiles in cecal contents were determined by shotgun metagenomic sequencing. CMC treatment significantly increased fecal Lcn-2 levels compared to P80 and water treatment by one week and throughout the experiment. Likewise, CMC treatment increased histologic inflammatory scores and colonic inflammatory cytokine gene expression compared with P80 and water controls. The two emulsifiers differentially affected specific intestinal microbiota. CMC did not impact bacterial composition but significantly decreased Caudoviricetes (bacteriophages), while P80 exposure non-significantly increased the abundance of both Actinobacteria and Proteobacteria. Commonly used dietary emulsifiers have different abilities to induce colitis in humanized mice. CMC promotes more aggressive inflammation without changing bacterial composition.


Assuntos
Carboximetilcelulose Sódica/efeitos adversos , Colite/induzido quimicamente , Colite/microbiologia , Emulsificantes/efeitos adversos , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais/microbiologia , Polissorbatos/efeitos adversos , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Colite/patologia , Colo/metabolismo , Colo/patologia , Fezes/microbiologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/patologia , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
14.
Nutrients ; 13(10)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34684320

RESUMO

Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease. Probiotics have a potential beneficial effect on the prevention of UC onset and relapse in clinical trials. Lactobacillus rhamnosus GG (L. rhamnosus GG) have shown clinical benefits on UC patients, however, the precise mechanisms are unknown. The aim of this study is to explore the effect of extracellular vesicles released from L. rhamnosus GG (LGG-EVs) on dextran sulfate sodium (DSS)-induced colitis and propose the underlying mechanism of LGG-EVs for protecting against colitis. The results showed that LGG-EVs could prevent colonic tissue damage and shortening of the colon (p < 0.01), and ameliorate intestinal inflammation by inhibiting TLR4-NF-κB-NLRP3 axis activation. Consistently, the pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-2) were suppressed effectively upon LGG-EVs treatment (p < 0.05). The 16S rRNA sequencing showed that LGG-EVs administration could reshape the gut microbiota in DSS-induced colitis mice, which further alters the metabolism pathways of gut microbiota. These findings propose a novel perspective of L. rhamnosus GG in attenuating inflammation mediated by extracellular vesicles and offer consideration for developing oral gavage of LGG-EVs for colitis therapies.


Assuntos
Vesículas Extracelulares/metabolismo , Microbioma Gastrointestinal , Inflamação/microbiologia , Lactobacillus rhamnosus/metabolismo , Animais , Biodiversidade , Colite/induzido quimicamente , Colite/genética , Colite/microbiologia , Colite/patologia , Citocinas/metabolismo , Sulfato de Dextrana , Vesículas Extracelulares/ultraestrutura , Ácidos Graxos/metabolismo , Regulação da Expressão Gênica , Inflamação/genética , Inflamação/imunologia , Masculino , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Especificidade de Órgãos , Análise de Componente Principal
15.
Int J Nanomedicine ; 16: 6889-6904, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675513

RESUMO

Introduction: Excessive production of reactive oxygen species (ROS) to induce high oxidative stress is one of the main causes of colitis; thus, it has been regarded as a therapeutic target for colitis treatment. And the nanomaterial-based therapeutic strategies are effective against colitis. However, the previous elaborately designed materials exhibit limited application due to the uncertain biocompatibility and complicated manufacturing processes. Methods: In this study, the highly monodisperse hollow CeO2 nanoparticles (H-CeO2) with uniform morphology were obtained by in situ growing CeO2 on solid silica nanoparticles and subsequently removing the silica core. The H-CeO2 was further modified with PEG, which owned excellent biological stability and biocompatibility. The experimental model of colitis induced by dextran sulfate sodium (DSS) was used to investigate the anti-inflammatory effect of H-CeO2-PEG. Results: The H-CeO2-PEG showed good ROS scavenging efficacy and decreased the levels of proinflammatory cytokines (IL-6, IL-1ß, IL-18, and TNF-α) in DSS-induced colitis mice. Furthermore, H-CeO2-PEG inhibited the activation of the MAPK signalling pathway to alleviate colitis. Conclusion: This study reveals the therapeutic effects of CeO2-based nanomedicine toward colitis and elucidates the specific signalling pathway involved, which provides potential alternative therapeutic options for patients with inflammation tissue.


Assuntos
Colite , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Sulfato de Dextrana , Humanos , Inflamação , Camundongos , Estresse Oxidativo , Espécies Reativas de Oxigênio
16.
Microbiome ; 9(1): 184, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493333

RESUMO

BACKGROUND: Alteration of the gut microbiota may contribute to the development of inflammatory bowel disease (IBD). Epigallocatechin-3-gallate (EGCG), a major bioactive constituent of green tea, is known to be beneficial in IBD alleviation. However, it is unclear whether the gut microbiota exerts an effect when EGCG attenuates IBD. RESULTS: We first explored the effect of oral or rectal EGCG delivery on the DSS-induced murine colitis. Our results revealed that anti-inflammatory effect and colonic barrier integrity were enhanced by oral, but not rectal, EGCG. We observed a distinct EGCG-mediated alteration in the gut microbiome by increasing Akkermansia abundance and butyrate production. Next, we demonstrated that the EGCG pre-supplementation induced similar beneficial outcomes to oral EGCG administration. Prophylactic EGCG attenuated colitis and significantly enriched short-chain fatty acids (SCFAs)-producing bacteria such as Akkermansia and SCFAs production in DSS-induced mice. To validate these discoveries, we performed fecal microbiota transplantation (FMT) and sterile fecal filtrate (SFF) to inoculate DSS-treated mice. Microbiota from EGCG-dosed mice alleviated the colitis over microbiota from control mice and SFF shown by superiorly anti-inflammatory effect and colonic barrier integrity, and also enriched bacteria such as Akkermansia and SCFAs. Collectively, the attenuation of colitis by oral EGCG suggests an intimate involvement of SCFAs-producing bacteria Akkermansia, and SCFAs, which was further demonstrated by prophylaxis and FMT. CONCLUSIONS: This study provides the first data indicating that oral EGCG ameliorated the colonic inflammation in a gut microbiota-dependent manner. Our findings provide novel insights into EGCG-mediated remission of IBD and EGCG as a potential modulator for gut microbiota to prevent and treat IBD. Video Abstract.


Assuntos
Colite , Microbioma Gastrointestinal , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Sulfato de Dextrana , Modelos Animais de Doenças , Homeostase , Camundongos , Camundongos Endogâmicos C57BL , Polifenóis/farmacologia , Chá
17.
J Agric Food Chem ; 69(36): 10506-10514, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34478286

RESUMO

The present study investigated the effect of eugenol (EUG) on dextran sulfate sodium (DSS)-induced colitis and explored the underlying mechanisms. C57BL/6 mice were intragastrically administered normal saline or EUG (20 mg/kg body weight) for 17 days, and colitis was induced by using 3% DSS from day 7. The results showed that EUG increased the body weight and reduced the disease activity index score and colon pathological scores in DSS-treated mice (P < 0.05). Further, EUG preserved the proinflammatory cytokines (interleukin (IL)-6, -12, -21, and -23), lowered (P < 0.05) colonic malondialdehyde (MDA), uncoupling protein 2 (UCP2) expression and p65 phosphorylation, and activated (P < 0.05) colonic kelch-like ECH-associated protein 1 and nuclear factor (erythroid-derived 2)-like 2 expressions but did not affect the intestinal microbiota in DSS-treated mice. Furthermore, EUG ameliorated colitis in antibiotic-treated mice, while fecal microbiota transplantation from EUG preadministered mice failed to ameliorate colitis. In conclusion, EUG could alleviate colitis by attenuating colonic inflammation and oxidative stress independent of intestinal microbiota.


Assuntos
Colite , Microbioma Gastrointestinal , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/genética , Colo , Citocinas/genética , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Eugenol , Camundongos , Camundongos Endogâmicos C57BL
18.
BMC Gastroenterol ; 21(1): 350, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556042

RESUMO

BACKGROUND: Olmesartan, which is an angiotensin II receptor blocker, reportedly causes spruelike enteropathy, with intestinal villous atrophy as its typical histopathological finding. Interestingly, collagenous and/or lymphocytic gastritis and colitis occur in some patients. We report the case of a 73-year-old Japanese man with a 2-month clinical history of severe diarrhea and weight loss. There were few reports in which spruelike enteropathy and collagenous colitis were both observed and could be followed up. CASE PRESENTATION: We report a case of a 73-year-old man with a 2-month clinical history of severe diarrhea and weight loss. He had taken olmesartan for hypertension treatment for 5 years. Endoscopic examination with biopsies revealed intestinal villous atrophy and collagenous colitis. Suspecting enteropathy caused by olmesartan, which was discontinued on admission because of hypotension, we continued to stop the drug. Within 3 weeks after olmesartan discontinuation, his clinical symptoms improved. After 3 months, follow-up endoscopy showed improvement of villous atrophy but not of the thickened collagen band of the colon. However, the mucosa normalized after 6 months, histologically confirming that the preexistent pathology was finally resolved. CONCLUSIONS: This report presents a case in which spruelike enteropathy and collagenous colitis were both observed and could be followed up. In unexplained cases of diarrhea, medication history should be reconfirmed and this disease should be considered a differential diagnosis.


Assuntos
Colite Colagenosa , Colite , Idoso , Colite/induzido quimicamente , Colite/diagnóstico , Colite Colagenosa/induzido quimicamente , Colite Colagenosa/diagnóstico , Diarreia/induzido quimicamente , Humanos , Imidazóis/efeitos adversos , Masculino , Tetrazóis/efeitos adversos
19.
Int J Mol Sci ; 22(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34502199

RESUMO

5,6-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid (5,6-DiHETE) is an eicosapentaenoic acid-derived newly discovered bioactive anti-inflammatory lipid mediator having diverse functions. Here, we assessed the potential of orally administered 5,6-DiHETE in promoting healing of dextran sulfate sodium (DSS)-induced colitis in mice. We measured the plasma concentrations of 5,6-DiHETE in untreated mice before and 0.5, 1, 3, and 6 h after its oral administration (150 or 600 µg/kg) in mice. Mice developed colitis by DSS (2% in drinking water for 4 days), and 5,6-DiHETE (150 or 600 µg/kg/day) was orally administered from day 9 to 14. Next, the faecal hardness and bleeding were assessed, and the dissected colons on day 14 via H&E staining. The plasma concentration of 5,6-DiHETE reached 25.05 or 44.79 ng/mL 0.5 h after the administration of 150 or 600 µg/kg, respectively, followed by a gradual decrease. The half-life of 5,6-DiHETE was estimated to be 1.25-1.63 h. Diarrhoea deteriorated after day 3 and peaked on day 5, followed by a gradual recovery. Histological assessment on day 14 showed DSS-mediated granulocyte infiltration, mucosal erosion, submucosal edema, and cryptal abscesses in mice. Oral administration of 150 or 600 µg/kg/day of 5,6-DiHETE accelerated the recovery from the DSS-induced diarrhoea and significantly ameliorated colon inflammation. The therapeutic effect of 600 µg/kg/day 5,6-DiHETE was slightly stronger than that by 150 µg/kg/day. Our study reveals attenuation of DSS-induced colitis in mice by the oral administration of 5,6-DiHETE dose-dependently, thereby suggesting a therapeutic potential of 5,6-DiHETE for inflammatory bowel disease.


Assuntos
Anti-Inflamatórios/farmacologia , Colite/tratamento farmacológico , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/farmacologia , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Colite/induzido quimicamente , Colite/patologia , Ácido Eicosapentaenoico/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL
20.
Biomater Sci ; 9(19): 6584-6596, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34582526

RESUMO

Glycogen synthase kinase-3ß (GSK3ß), a multi-functional kinase, is a promising therapeutic target for the treatment of inflammation. Inhibitory κB kinase (IKK)-activated GSK3ß inhibitory peptide (IAGIP) was designed as an inflammation-responsive anti-colitic therapeutic. To optimize therapeutic efficiency, IAGIP was tested using two different drug delivery techniques: colon-targeted delivery and cell-permeable peptide modification. In cell-based experiments, in response to tumor necrosis factor (TNF)- and lipopolysaccharide (LPS)-mediated activation of IKK, cell-permeable IAGIP (CTP-IAGIP) inhibited GSK3ß, leading to increased production of anti-inflammatory cytokine interleukin-10 (IL-10) and suppression of TNF- and LPS-induced NFκB activity. Oral gavage of CTP-IAGIP loaded in the colon-targeted capsule attenuated 2,4,6-trinitrobenzene sulfonic acid-induced rat colitis and lowered the expression levels of NFκB-regulated proteins in the inflamed colons. CTP-IAGIP further induced IL-10 production in the inflamed colonic tissues; however, the levels of IL-10 were not affected in the normal colonic tissue or colonic tissue in which inflammation had subsided. Collectively, our data suggest that IAGIP administered using the aforementioned drug delivery techniques is an orally active anti-colitic drug selectively responding to inflammation.


Assuntos
Colite , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Glicogênio Sintase Quinase 3 beta , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Peptídeos , Ratos , Ácido Trinitrobenzenossulfônico
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