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Minerva Gastroenterologica E Dietologica Jun 2020Eosinophilic colitis (EC) is a rare inflammatory disease included in the chapter of eosinophilic gastrointestinal disorders (EGIDs), diagnosed by the presence of primary... (Review)
Review
Eosinophilic colitis (EC) is a rare inflammatory disease included in the chapter of eosinophilic gastrointestinal disorders (EGIDs), diagnosed by the presence of primary eosinophilic infiltrate in the colon wall in symptomatic patients. While the etiology of primary colonic eosinophilia is unknown, several conditions are involved in the pathogenesis of secondary eosinophilic colonic infiltrate (food allergens, parasitic infections, drugs), which have to be excluded in order to correctly diagnose the primary form of the disease. Up to now, EC is lacking of codified guidelines regarding diagnostic criteria (especially eosinophil threshold values) and treatment, thus a correct approach to EC remains very challenging. Imaging, laboratory tests and endoscopy might be helpful in ruling out other mimic conditions, but EC is still a diagnosis of exclusion. Several treatment options are feasible, but most of the evidences are drawn from case reports and small case series, thus limiting their value. We carried out a review of the current literature to evaluate the more appropriate and modern clinical strategy for diagnosis and management of EC.
Topics: Colitis; Enteritis; Eosinophilia; Gastritis; Humans
PubMed: 31994372
DOI: 10.23736/S1121-421X.20.02656-2 -
Microbiome Sep 2021Alteration of the gut microbiota may contribute to the development of inflammatory bowel disease (IBD). Epigallocatechin-3-gallate (EGCG), a major bioactive constituent...
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.
Topics: Animals; Colitis; Dextran Sulfate; Disease Models, Animal; Gastrointestinal Microbiome; Homeostasis; Mice; Mice, Inbred C57BL; Polyphenols; Tea
PubMed: 34493333
DOI: 10.1186/s40168-021-01115-9 -
Microbiome Sep 2022The pathogenesis of inflammatory bowel diseases (IBD) is multifactorial, and diagnostic and treatment strategies for IBD remain to be developed. RhoB regulates multiple...
BACKGROUND
The pathogenesis of inflammatory bowel diseases (IBD) is multifactorial, and diagnostic and treatment strategies for IBD remain to be developed. RhoB regulates multiple cell functions; however, its role in colitis is unexplored.
RESULTS
Here, we found RhoB was dramatically increased in colon tissues of ulcerative colitis (UC) patients and mice with DSS-induced colitis. Compared with wild type mice, RhoB and RhoB mice developed milder DSS-induced colitis and increased goblet cell numbers and IEC proliferation. Decreased RhoB promoted goblet cell differentiation and epithelial regeneration through inhibiting Wnt signaling pathway and activating p38 MAPK signaling pathway. Moreover, increased SCFA-producing bacteria and SCFA concentrations were detected in intestinal microbiome of both RhoB and RhoB mice and upregulated SCFA receptor expression was also observed.
CONCLUSIONS
Taken together, a higher level of RhoB is associated with UC, which also contributes to UC development through modulating cell signaling and altering intestinal bacterial composition and metabolites. These observations suggest that RhoB has potential as a biomarker and a treatment target for UC. Video Abstract.
Topics: Animals; Biomarkers; Colitis; Colitis, Ulcerative; Dextran Sulfate; Gastrointestinal Microbiome; Humans; Mice; Signal Transduction; p38 Mitogen-Activated Protein Kinases; rhoB GTP-Binding Protein
PubMed: 36114582
DOI: 10.1186/s40168-022-01347-3 -
Gut Microbes 2022Imbalance of gut microbiota homeostasis is related to the occurrence of ulcerative colitis (UC), and probiotics are thought to modulate immune microenvironment and...
Imbalance of gut microbiota homeostasis is related to the occurrence of ulcerative colitis (UC), and probiotics are thought to modulate immune microenvironment and repair barrier function. Here, in order to reveal the interaction between UC and gut microbiota, we screened a new probiotic strain by 16S rRNA sequencing from Dextran Sulfate Sodium (DSS)-induced colitis mice, and explored the mechanism and clinical relevance. (), as a potential anti-inflammatory bacterium was decreased colonization in colitis mice. Gavage could alleviate colitis by specifically increasing the proportion of intestinal macrophages and the secretion of Il-10 with macrophages depleted model and in mice. We identified this subset of immune cells activated as CD206 macrophages. Mechanistically, supplementation enhanced the mobilization of CD206 macrophages through the activation of STAT3 and . In addition, we revealed that TLR1/2 was essential for the activation of STAT3 and the recognition of by macrophages. Clinically, there was positive correlation between the abundance of and the expression level of and in UC tissues. could activate native macrophages into CD206 macrophages and release IL-10 through TLR1/2-STAT3 pathway to relieve experimental colitis. may serve as an immunomodulator and anti-inflammatory therapeutic target for UC.
Topics: Animals; Mice; Anti-Inflammatory Agents; Colitis; Colitis, Ulcerative; Dextran Sulfate; Gastrointestinal Microbiome; Interleukin-10; Lactobacillus johnsonii; Macrophages; RNA, Ribosomal, 16S; Toll-Like Receptor 1
PubMed: 36398889
DOI: 10.1080/19490976.2022.2145843 -
Phytomedicine : International Journal... Mar 2023Wumei Wan (WMW) has been used to address digestive disorder for centuries in traditional Chinese medicine. Previous studies have demonstrated its anti-colitis efficacy,...
BACKGROUND
Wumei Wan (WMW) has been used to address digestive disorder for centuries in traditional Chinese medicine. Previous studies have demonstrated its anti-colitis efficacy, but the underlying mechanism of its action remains to be further clarified.
PURPOSE
To investigate the underlying mechanisms of WMW in the treatment of chronic ulcerative colitis (UC) through network pharmacology and experimental validation.
METHODS
Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform were used to identify the ingredients and potential targets of WMW. The microarray gene data GSE75214 datasets from GEO database was used to define UC-associated targets. Cytoscape3.7.2 was employed to construct the protein-protein interaction (PPI) network and compounds-disease targets network. GO enrichment analysis and KEGG pathway analysis were performed by R software for functional annotation. UPLC-TOF-MS/MS method was used to quantitatively analyze the active ingredients of WMW. For experimental validation, three cycles of 2% dextran sulfate sodium salt (DSS) were used to construct chronic colitis model. The hub targets and signal pathway were detected by qPCR, ELISA, western blotting , immunohistochemical and immunofluorescence.
RESULTS
Through network analysis, 104 active ingredients were obtained from WMW, and 47 of these ingredients had potential targets for UC. A total of 41 potential targets of WMW and 13 hub targets were identified. KEGG analysis showed that WMW involved in advanced glycation end products-receptor of advanced glycation end products (AGE-RAGE) signaling pathway. Taxifolin, rutaecarpine, kaempferol, quercetin, and luteolin of WMW were the more highly predictive components related to the AGE-RAGE signaling pathway. In vivo validation, WMW improved DSS-induced colitis, reduced the expression of inflammatory cytokines and chemokines. Notably, it significantly decreased the mRNA expression of Spp1, Serpine1, Mmp2, Mmp9, Ptgs2, Nos2, Kdr and Icam1, which were associated with angiogenesis. In addition, we confirmed WMW inhibited RAGE expression and diminished DSS-induced epithelial barrier alterations CONCLUSION: Our results initially demonstrated the effective components and the strong anti-angiogenic activity of WMW in experimental chronic colitis. Sufficient evidence of the satisfactory anti-colitis action of WMW was verified in this study, suggesting its potential as a quite prospective agent for the therapy of UC.
Topics: Humans; Colitis; Colitis, Ulcerative; Drugs, Chinese Herbal; Inflammation; Medicine, Chinese Traditional; Molecular Docking Simulation; Network Pharmacology; Prospective Studies; Signal Transduction; Tandem Mass Spectrometry
PubMed: 36706698
DOI: 10.1016/j.phymed.2023.154658 -
Cancer Treatment Reviews Sep 2022Immune checkpoint inhibitors (ICIs) have improved cancer outcomes. However, immune-related adverse effects are common. The aim was to investigate the incidence of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Immune checkpoint inhibitors (ICIs) have improved cancer outcomes. However, immune-related adverse effects are common. The aim was to investigate the incidence of diarrhea and colitis of ICIs alone and in combination with chemotherapy or tyrosine kinase inhibitors (TKIs), histopathological findings, and management.
METHODS
Two separate studies, including meta-analyses, were performed. Key inclusion criteria were for Study I) phase I-IV trials, and data on diarrhea and/or colitis; for Study II) studies describing histopathologic and endoscopic findings and/or biologic treatment for ICI-induced colitis.
RESULTS
The incidence of anti-PD-1/PD-L1 antibody-induced diarrhea and colitis was 10% and 2%, respectively, with no clinically relevant differences between the compounds. The CTLA-4 inhibitor, ipilimumab, induced diarrhea and colitis in 33% and 7% of patients, respectively, whereas the incidence of diarrhea and colitis following ipilimumab combined with nivolumab was 21%-37% and 4%-8%, depending on regimen. The incidence of all-grade diarrhea following ICIs combined with chemotherapy or TKIs was high (17%-56%), whereas only 0.5% of patients developed severe (≥grade 3) colitis. The main patterns of histopathologic presentation after PD-1/CTLA-4 inhibitor mono- or combination therapy were acute and chronic active colitis and microscopic colitis-like. Infliximab and vedolizumab were equally effective against ICI-induced colitis.
CONCLUSION
Expanding treatment options include combinations of ICIs and chemotherapy/TKI with a high incidence of diarrhea and a low incidence of colitis; thus, a potential risk of overtreatment with corticosteroids exists. We suggest a more tailored approach, particularly for the management of low-grade diarrhea. Prospective clinical trials are needed to refine management.
Topics: Colitis; Diarrhea; Humans; Immune Checkpoint Inhibitors; Incidence; Ipilimumab; Prospective Studies
PubMed: 35917654
DOI: 10.1016/j.ctrv.2022.102440 -
Methods in Molecular Biology (Clifton,... 2016Our understanding of colitis-associated carcinoma (CAC) has benefited substantially from mouse models that faithfully recapitulate human CAC. Chemical models, in...
Our understanding of colitis-associated carcinoma (CAC) has benefited substantially from mouse models that faithfully recapitulate human CAC. Chemical models, in particular, have enabled fast and efficient analysis of genetic and environmental modulators of CAC without the added requirement of time-intensive genetic crossings. Here we describe the Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) mouse model of inflammatory colorectal cancer.
Topics: Animals; Azoxymethane; Colitis; Colorectal Neoplasms; Dextran Sulfate; Disease Models, Animal; Humans; Mice
PubMed: 27246042
DOI: 10.1007/978-1-4939-3603-8_26 -
Gastroenterology Apr 2023Colorectal cancer is a leading cause of cancer death, and a major risk factor is chronic inflammation. Despite the link between colitis and cancer, the mechanism by...
BACKGROUND & AIMS
Colorectal cancer is a leading cause of cancer death, and a major risk factor is chronic inflammation. Despite the link between colitis and cancer, the mechanism by which inflammation leads to colorectal cancer is not well understood.
METHODS
To investigate whether different forms of inflammation pose the same risk of cancer, we compared several murine models of colitis (dextran sodium sulfate [DSS], 2,4,6-trinitrobenzene sulfonic acid, 4-ethoxylmethylene-2-phenyloxazol-5-one, Citrobacter rodentium, Fusobacterium nucleatum, and doxorubicin) with respect to their ability to lead to colonic tumorigenesis. We attempted to correlate the severity of colitis and inflammatory profile with the risk of tumorigenesis in both azoxymethane-dependent and Dclk1/APC murine models of colitis-associated cancer.
RESULTS
DSS colitis reproducibly led to colonic tumors in both mouse models of colitis-associated cancer. In contrast, all other forms of colitis did not lead to cancer. When compared with the colitis not associated with tumorigenesis, DSS colitis was characterized by significantly increased CD11bF4/80Ly6C macrophages and CD11bLy6G neutrophils. Interestingly, depletion of the CD11bF4/80Ly6C macrophages inhibited tumorigenesis, whereas depletion of CD11bLy6G neutrophils had no effect on tumorigenesis. Furthermore, the macrophage-derived cytokines interleukin-1β, tumor necrosis factor-α, and interleukin-6 were significantly increased in DSS colitis and promoted stemness of Dclk1 tuft cells that serve as the cellular origin of cancer.
CONCLUSIONS
We have identified CD11bF4/80Ly6C macrophages as key mediators of cancer initiation in colitis-associated cancer. Development of new therapies that target these cells may provide an effective preventative strategy for colitis-associated cancer.
Topics: Animals; Mice; Azoxymethane; Carcinogenesis; Cell Plasticity; Colitis; Colitis-Associated Neoplasms; Dextran Sulfate; Disease Models, Animal; Inflammation; Macrophages; Mice, Inbred C57BL
PubMed: 36634827
DOI: 10.1053/j.gastro.2023.01.002 -
Frontiers in Immunology 2022Ulcerative colitis (UC) is a chronic and recurrent inflammatory disorder in the gastrointestinal tract. Here, we examined the pharmacological effects of ginsenoside Rg1,...
Ulcerative colitis (UC) is a chronic and recurrent inflammatory disorder in the gastrointestinal tract. Here, we examined the pharmacological effects of ginsenoside Rg1, a natural compound with low bioavailability, on the acute experimental colitis mice induced by dextran sulfate sodium (DSS) and explored underlying mechanisms. Acute UC was induced in C57BL/6 mice by 2.5% DSS for 7 days, meanwhile, 2 mg/10 g b.w. ginsenoside Rg1 was administrated to treat the mice. Body weight, colon length, colon tissue pathology, and colon tissue inflammatory cytokines were assessed. The composition structure of gut microbiota was profiled using 16s rRNA sequencing. Global metabolomic profiling of the feces was performed, and tryptophan and its metabolites in the serum were detected. The results showed that Rg1 significantly ameliorated DSS-induced colonic injury and colonic inflammation. In addition, Rg1 also partly reversed the imbalance of gut microbiota composition caused by DSS. Rg1 intervention can regulate various metabolic pathways of gut microbiota such as valine, leucine, and isoleucine biosynthesis and vitamin B6 metabolism and the most prominent metabolic alteration was tryptophan metabolism. DSS decreased the levels of tryptophan metabolites in the serum, including indole-3-carboxaldehyde, indole-3-lactic acid, 3-indolepropionic acid, and niacinamide and Rg1 can increase the levels of these metabolites. In conclusion, the study discovered that Rg1 can protect the intestinal barrier and alleviate colon inflammation in UC mice, and the underlying mechanism is closely related to the regulation of gut microbiota composition and microbial tryptophan metabolism.
Topics: Animals; Colitis; Colitis, Ulcerative; Dextran Sulfate; Gastrointestinal Microbiome; Ginsenosides; Inflammation; Mice; Mice, Inbred C57BL; RNA, Ribosomal, 16S; Tryptophan
PubMed: 35655785
DOI: 10.3389/fimmu.2022.817600 -
Cell Host & Microbe Apr 2023Drug platforms that enable the directed delivery of therapeutics to sites of diseases to maximize efficacy and limit off-target effects are needed. Here, we report the...
Drug platforms that enable the directed delivery of therapeutics to sites of diseases to maximize efficacy and limit off-target effects are needed. Here, we report the development of PROTEcT, a suite of commensal Escherichia coli engineered to secrete proteins directly into their surroundings. These bacteria consist of three modular components: a modified bacterial protein secretion system, the associated regulatable transcriptional activator, and a secreted therapeutic payload. PROTEcT secrete functional single-domain antibodies, nanobodies (Nbs), and stably colonize and maintain an active secretion system within the intestines of mice. Furthermore, a single prophylactic dose of a variant of PROTEcT that secretes a tumor necrosis factor-alpha (TNF-α)-neutralizing Nb is sufficient to ablate pro-inflammatory TNF levels and prevent the development of injury and inflammation in a chemically induced model of colitis. This work lays the foundation for developing PROTEcT as a platform for the treatment of gastrointestinal-based diseases.
Topics: Animals; Mice; Escherichia coli; Single-Domain Antibodies; Colitis; Tumor Necrosis Factor-alpha
PubMed: 37003258
DOI: 10.1016/j.chom.2023.03.007