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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 -
American Family Physician May 2013Ulcerative colitis is a chronic inflammatory disease of the colon. The etiology is unknown. Risk factors include a history of recent infection with Salmonella or... (Review)
Review
Ulcerative colitis is a chronic inflammatory disease of the colon. The etiology is unknown. Risk factors include a history of recent infection with Salmonella or Campylobacter, living in Western industrialized nations and at higher latitudes, and a family history of the disease. The incidence peaks in early adulthood, but patients can develop the disorder from early childhood through adulthood. Ulcerative colitis often presents with abdominal pain, diarrhea, and hematochezia. It is important to exclude infectious etiologies. Anemia and an elevated erythrocyte sedimentation rate or C-reactive protein level may suggest inflammatory bowel disease, but the absence of laboratory abnormalities does not rule out ulcerative colitis. The diagnosis is suspected clinically and confirmed through endoscopic biopsy. First-line treatment is therapy with 5-aminosalicylic acid. Corticosteroids may be added if 5-aminosalicylic acid therapy is ineffective. Infliximab can be added to induce and sustain remission. Patients with severe or nonresponsive ulcerative colitis should be hospitalized, and intravenous corticosteroids should be given. If medical management has been ineffective, surgical intervention is indicated for severe disease. Patients with ulcerative colitis have an increased risk of colon cancer and should have periodic colonoscopy beginning eight to 10 years after diagnosis.
Topics: Colitis, Ulcerative; Diagnosis, Differential; Humans; Risk Factors
PubMed: 23939448
DOI: No ID Found -
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 -
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 -
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 -
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 -
Microbiology Spectrum Aug 2022Microbiological treatments are expected to have a role in the future management of inflammatory bowel disease (IBD). Clostridium butyricum () is a probiotic...
Microbiological treatments are expected to have a role in the future management of inflammatory bowel disease (IBD). Clostridium butyricum () is a probiotic microorganism that exhibits beneficial effects on various disease conditions. Although many studies have revealed that C. butyricum provides protective effects in mice with colitis, the way C. butyricum establishes beneficial results in the host remains unclear. In this study, we investigated the mechanisms by which C. butyricum modifies the gut microbiota, produces bacterial metabolites that may be involved, and, specifically, how microbial extracellular vesicles (EVs) positively influence IBD, using a dextran sulfate sodium (DSS)-induced colitis murine model in mice. First, we showed that C. butyricum provides a protective effect against colitis, as evidenced by the prevention of body weight loss, a reduction in the disease activity index (DAI) score, a shortened colon length, decreased histology score, and an improved gut barrier function, accompanied by reduced levels of pathogenic bacteria, including Escherichia/Shigella, and an increased relative abundance of butyrate-producing Clostridium sensu stricto-1 and . Second, we also confirmed that the gut microbiota and metabolites produced by C. butyricum played key roles in the attenuation of DSS-induced experimental colitis, as supported by the profound alleviation of colitis effects following fecal transplantation or fecal filtrate insertion supplied from C. butyricum-treated mice. Finally, C. butyricum-derived EVs protected the gut barrier function, improved gut microbiota homeostasis in ulcerative colitis, and contributed to overall colitis alleviation. This study indicated that C. butyricum provided a prevention effect against colitis mice, which involved protection of the intestinal barrier and positively regulating gut microbiota. Furthermore, we confirmed that the gut microbiota and metabolites that were induced by C. butyricum also contributed to the attenuation of DSS-induced colitis. Importantly, C. butyricum-derived EVs showed an effective impact in alleviating colitis.
Topics: Animals; Clostridium butyricum; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Extracellular Vesicles; Homeostasis; Inflammatory Bowel Diseases; Mice
PubMed: 35762770
DOI: 10.1128/spectrum.01368-22 -
Gut Jul 2023The extent to which tryptophan (Trp) metabolism alterations explain or influence the outcome of inflammatory bowel diseases (IBDs) is still unclear. However, several Trp...
OBJECTIVE
The extent to which tryptophan (Trp) metabolism alterations explain or influence the outcome of inflammatory bowel diseases (IBDs) is still unclear. However, several Trp metabolism end-products are essential to intestinal homeostasis. Here, we investigated the role of metabolites from the kynurenine pathway.
DESIGN
Targeted quantitative metabolomics was performed in two large human IBD cohorts (1069 patients with IBD). Dextran sodium sulphate-induced colitis experiments in mice were used to evaluate effects of identified metabolites. In vitro, ex vivo and in vivo experiments were used to decipher mechanisms involved. Effects on energy metabolism were evaluated by different methods including Single Cell mEtabolism by profiling Translation inHibition.
RESULTS
In mice and humans, intestinal inflammation severity negatively correlates with the amount of xanthurenic (XANA) and kynurenic (KYNA) acids. Supplementation with XANA or KYNA decreases colitis severity through effects on intestinal epithelial cells and T cells, involving Aryl hydrocarbon Receptor (AhR) activation and the rewiring of cellular energy metabolism. Furthermore, direct modulation of the endogenous tryptophan metabolism, using the recombinant enzyme aminoadipate aminotransferase (AADAT), responsible for the generation of XANA and KYNA, was protective in rodent colitis models.
CONCLUSION
Our study identified a new mechanism linking Trp metabolism to intestinal inflammation and IBD. Bringing back XANA and KYNA has protective effects involving AhR and the rewiring of the energy metabolism in intestinal epithelial cells and CD4 T cells. This study paves the way for new therapeutic strategies aiming at pharmacologically correcting its alterations in IBD by manipulating the endogenous metabolic pathway with AADAT.
Topics: Humans; Animals; Mice; Tryptophan; Inflammatory Bowel Diseases; Colitis; Intestines; Inflammation
PubMed: 36270778
DOI: 10.1136/gutjnl-2022-327337 -
Frontiers in Immunology 2022In clinical practice, fecal microbiota transplantation (FMT) has been used to treat inflammatory bowel disease (IBD), and has shown certain effects. However, the...
In clinical practice, fecal microbiota transplantation (FMT) has been used to treat inflammatory bowel disease (IBD), and has shown certain effects. However, the selection of FMT donors and the mechanism underlying the effect of FMT intervention in IBD require further exploration. In this study, dextran sodium sulfate (DSS)-induced colitis mice were used to determine the differences in the protection of colitis symptoms, inflammation, and intestinal barrier, by FMT from two donors. Intriguingly, pre-administration of healthy bacterial fluid significantly relieved the symptoms of colitis compared to the ulcerative colitis (UC) bacteria. In addition, healthy donor (HD) bacteria significantly reduced the levels of inflammatory markers Myeloperoxidase (MPO) and Eosinophil peroxidase (EPO), and various pro-inflammatory factors, in colitis mice, and increased the secretion of the anti-inflammatory factor IL-10. Metagenomic sequencing indicated higher species diversity and higher abundance of anti-inflammatory bacteria in the HD intervention group, including , , , short-chain fatty acids (SCFAs)-producing bacterium , and secondary bile acids (SBAs)-producing bacterium . In the UC intervention group, the SCFA-producing bacterium , IBD-related bacterium , , and the conditional pathogen , were more abundant. Metabolomics analysis showed that the two types of FMT significantly modulated the metabolism of DSS-induced mice. Moreover, compared with the UC intervention group, indoleacetic acid and unsaturated fatty acids (DHA, DPA, and EPA) with anti-inflammatory effects were significantly enriched in the HD intervention group. In summary, these results indicate that FMT can alleviate the symptoms of colitis, and the effect of HD intervention is better than that of UC intervention. This study offers new insights into the mechanisms of FMT clinical intervention in IBD.
Topics: Animals; Anti-Inflammatory Agents; Bacteria; Colitis; Colitis, Ulcerative; Dextran Sulfate; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Humans; Mice
PubMed: 35237276
DOI: 10.3389/fimmu.2022.836542 -
Stem Cell Research & Therapy Jul 2021Human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes are recognized as novel cell-free therapeutic agents for inflammatory bowel disease (IBD), a...
BACKGROUND
Human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes are recognized as novel cell-free therapeutic agents for inflammatory bowel disease (IBD), a condition caused by dysregulated intestinal mucosal immunity. In this event, macrophage pyroptosis, a process of cell death following the activation of NLRP3 (NOD-like receptor family, pyrin domain-containing 3) inflammasomes, is believed to partially account for inflammatory reactions. However, the role of macrophage pyroptosis in the process of hucMSC-derived exosomes alleviating colitis remains unknown. This study aimed at exploring the therapeutic effect and mechanism of hucMSC-derived exosomes on colitis repair.
METHODS
In vivo, we used BALB/c mice to establish a dextran sulfate sodium (DSS)-induced colitis model and administrated hucMSC-derived exosomes intravenously to estimate its curative effect. Human myeloid leukemia mononuclear (THP-1) cells and mouse peritoneal macrophages (MPMs) were stimulated with lipopolysaccharides (LPS) and Nigericin to activate NLRP3 inflammasomes, which simulated an inflammation environment in vitro. A microRNA mimic was used to verify the role of miR-378a-5p/NLRP3 axis in the colitis repair.
RESULTS
hucMSC-derived exosomes inhibited the activation of NLRP3 inflammasomes in the mouse colon. The secretion of interleukin (IL)-18, IL-1β, and Caspase-1 cleavage was suppressed, resulting in reduced cell pyroptosis. The same outcome was observed in the in vitro cell experiments, where the co-culture of THP-1 cells and MPMs with hucMSC-derived exosomes caused decreased expression of NLRP3 inflammasomes and increased cell survival. Furthermore, miR-378a-5p was highly expressed in hucMSC-derived exosomes and played a vital function in colitis repair.
CONCLUSION
hucMSC-derived exosomes carrying miR-378a-5p inhibited NLRP3 inflammasomes and abrogated cell pyroptosis to protect against DSS-induced colitis.
Topics: Animals; Colitis; Exosomes; Macrophages; Mice; Mice, Inbred BALB C; MicroRNAs; NLR Family, Pyrin Domain-Containing 3 Protein; Pyroptosis; Umbilical Cord
PubMed: 34294138
DOI: 10.1186/s13287-021-02492-6