Cannabis for the treatment of Crohn's disease.
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ABSTRACT:
SUBMITTER: Kafil TS
PROVIDER: S-EPMC6517156 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) which can affect any part of the whole gastrointestinal tract (from mouth to anus). Malnutrition affects 65-75% of CD patients, and it is now well acknowledged that diet is of paramount importance in the management of the disease. In this review, we would like to highlight the most recent findings in the field of nutrition for the treatment of CD. Our analysis will cover a wide range of topics, from the well-established diets to the new nutritional theories, along with the recent progress in emerging research fields, such as nutrigenomics.
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Project description:The Relationship between Fecal Bile Acids and Microbiome Community Structure in Pediatric Crohn’s Disease
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Project description:Etrolizumab is an investigational monoclonal antibody that binds the β7 subunit of α4β7 and αEβ7 integrins. The relative contribution of α4β7 and αEβ7 to gut lymphocyte trafficking remains to be characterized. Here we show that αEβ7 is highly expressed on human intestinal CD8+ cytotoxic intraepithelial lymphocytes (IELs) and a small subset of proinflammatory CD4+ T cells. Dual blockade of α4β7 and αEβ7 reduced CD8+ T cell accumulation in the gut to a greater extent than single blockade of either pathway using a photo-convertible mouse model. αEβ7 blockade decreased T cell-epithelial interactions, increased the migratory speed and promoted egress of activated T cells. In Crohn’s disease patients treated with etrolizumab, a reduction of inflammatory genes and cytotoxic IEL gene signatures was observed. Concurrent blockade of α4β7 and αEβ7 increases reduction of cytotoxic IELs and inflammatory T cells in the gut mucosa through a stepwise inhibition of cell migration and tissue retention. The "SAMPLE_ID" sample characteristic is a sample identifier internal to Genentech.
2021-07-23 | GSE152316 | GEO
Project description:Crohn's disease (CD) and ulcerative colitis (UC) are immunologically-mediated, debilitating conditions resulting from destructive inflammation of the gastrointestinal tract. The pathogenesis of IBD is incompletely understood, but is considered to be the result of an abnormal immune response with a wide range of cell types and proteins involved. Natural Killer Group 2D (NKG2D) is an activating receptor constitutively expressed on human Natural Killer (NK), ?? T, mucosal-associated invariant T (MAIT), CD56? T, and CD8? T cells. Activation of NKG2D triggers cellular proliferation, cytokine production, and target cell killing. Research into the NKG2D mechanism of action has primarily been focused on cancer and viral infections where cytotoxicity evasion is a concern. In human inflammatory bowel disease (IBD) this system is less characterized, but the ligands have been shown to be highly expressed during intestinal inflammation and the following receptor activation may contribute to tissue degeneration. A recent phase II clinical trial showed that an antibody against NKG2D induced clinical remission of CD in some patients, suggesting NKG2D and its ligands to be of importance in the pathogenesis of CD. This review will describe the receptor and its ligands in intestinal tissues and the clinical potential of blocking NKG2D in Crohn's disease.
| S-EPMC5618646 | biostudies-other
Project description:Inflammatory bowel diseases (IBDs), including Crohn's disease (CD), are genetically linked to host pathways that implicate an underlying role for aberrant immune responses to intestinal microbiota. However, patterns of gut microbiome dysbiosis in IBD patients are inconsistent among published studies. Using samples from multiple gastrointestinal locations collected prior to treatment in new-onset cases, we studied the microbiome in the largest pediatric CD cohort to date. An axis defined by an increased abundance in bacteria which include Enterobacteriaceae, Pasteurellacaea, Veillonellaceae, and Fusobacteriaceae, and decreased abundance in Erysipelotrichales, Bacteroidales, and Clostridiales, correlates strongly with disease status. Microbiome comparison between CD patients with and without antibiotic exposure indicates that antibiotic use amplifies the microbial dysbiosis associated with CD. Comparing the microbial signatures between the ileum, the rectum, and fecal samples indicates that at this early stage of disease, assessing the rectal mucosal-associated microbiome offers unique potential for convenient and early diagnosis of CD.
| S-EPMC4059512 | biostudies-literature
Project description:UNITI-2 was a phase 3 clinical trial (ClinicalTrials.gov Identifier: NCT01369342) comparing the effects (both positive and negative) of an initial treatment with ustekinumab to a placebo over 8 weeks in patients with moderately to severely active Crohn's disease.
2022-09-08 | GSE207022 | GEO
Project description:Crohn's disease and ulcerative colitis are chronic, relapsing inflammatory disorders of the GI tract. In both Crohn's disease and ulcerative colitis, leukocytic infiltration of the mucosa is associated with epithelial damage. Recently, monoclonal antibodies directed against cell adhesion molecules (CAMs) involved in leukocyte extravasation have been developed. Natalizumab, the first drug brought to market targeting CAMs, is clinically effective but is associated with serious adverse effects including the uncommon, but often fatal, neurological disease progressive multifocal leukoencephalopathy. Vedolizumab targets a subset of the CAMs blocked by natalizumab and is currently in Phase III trials to study its efficacy and safety in patients with inflammatory bowel disease. Here, we discuss the current treatment options available for patients with Crohn's disease or ulcerative colitis, the history of CAM inhibitors, the current state of development of vedolizumab and its future role in inflammatory bowel disease, if approved by regulatory agencies.
| S-EPMC3557917 | biostudies-literature
Project description:AimThe different surgical options for patients with colonic Crohn's disease (CD) include segmental colectomy, subtotal colectomy or proctocolectomy with end ileostomy. We present a national, multicentre study, promoted by the Italian Society of Colorectal Surgery with the aim to collect benchmark data and national variations on multidisciplinary management and postoperative outcomes of patients undergoing surgery for colonic CD.MethodsAll adult patients having elective surgery for colonic CD from June 2018 to May 2019 were eligible for participation in this retrospective study. The primary outcome measure was postoperative morbidity within 30 days of surgery.ResultsOne hundred twenty-two patients were included: 55 subtotal colectomy, 30 segmental colectomy, 25 proctectomy and 12 proctocolectomy. Eighty-six patients (70.4%) were discussed at the inflammatory bowel disease (IBD) multidisciplinary team meeting (MDT) prior to surgery. This ranged from 76.6% for segmental colectomy to 60% for subtotal colectomy, 66.6% for proctocolectomy and 48% for proctectomy. The proportion of patients counselled by a stoma nurse preoperatively was 50%. Laparoscopy was associated with reduced postoperative morbidity (p = 0.017) and shorter length of hospital stay (p < 0.001), whilst pre-operative anti-TNF was associated with Dindo-Clavien ≥ 3 complications (p = 0.023) and longer in-hospital stay (p = 0.007). The main procedure performed (segmental colectomy, subtotal colectomy, proctocolectomy or proctectomy) was not associated with postoperative morbidity (p = 0.626).ConclusionsSurgery for colonic CD has a high rate of postoperative complications. Almost a third of the patients were not preoperatively discussed at the IBD MDT, whilst the use of minimally invasive surgery for surgical treatment of colonic CD ranges from 40 to 66%.
| S-EPMC8208904 | biostudies-literature
Project description:Stenosis is one of the most frequent local complications in Crohn's disease (CD). Surgery is not the ideal treatment because of the high rate of postoperative recurrence. Endoscopic balloon dilation (EBD) currently is the current treatment of choice for short strictures amenable to the procedure. However, it is not applicable or effective in all the cases, and it is not without related complications. Our goal was to summarize the published information regarding the use and the role of the stents in the treatment of CD stricture. A Medline search was performed on the terms "stricture," "stenosis," "stent" and "Crohn's disease."a total of 19 publications met our search criteria for an overall number of 65 patients. Placing a self-expanding metal stent (SEMS) may be a safe and effective alternative to EBD and/or surgical intervention in the treatment of short stenosis in patients with CD. Indications are the same as those for EBD. In addition, SEMS may be useful in stenosis refractory to EBD and may be suitable in the treatment of longer or more complex strictures that cannot be treated by EBD. With the current information, it seems that the best treatment option is the placement of a fully covered stent for a mean time of 4 weeks. Regarding the use of biodegradable stents, the information is limited and showing poor results.the use of stents in the treatment of strictures in CD should be taken into account either as a first endoscopic therapy or in case of EBD failure.
| S-EPMC4804954 | biostudies-other
Project description:BackgroundCrohn's disease (CD) has an unclear etiology, but there is growing evidence of a direct link with a dysbiotic microbiome. Many gut microbes have previously been associated with CD, but these have mainly been confounded with patients' ongoing treatments. Additionally, most analyses of CD patients' microbiomes have focused on microbes in stool samples, which yield different insights than profiling biopsy samples.ResultsWe sequenced the 16S rRNA gene (16S) and carried out shotgun metagenomics (MGS) from the intestinal biopsies of 20 treatment-naïve CD and 20 control pediatric patients. We identified the abundances of microbial taxa and inferred functional categories within each dataset. We also identified known human genetic variants from the MGS data. We then used a machine learning approach to determine the classification accuracy when these datasets, collapsed to different hierarchical groupings, were used independently to classify patients by disease state and by CD patients' response to treatment. We found that 16S-identified microbes could classify patients with higher accuracy in both cases. Based on follow-ups with these patients, we identified which microbes and functions were best for predicting disease state and response to treatment, including several previously identified markers. By combining the top features from all significant models into a single model, we could compare the relative importance of these predictive features. We found that 16S-identified microbes are the best predictors of CD state whereas MGS-identified markers perform best for classifying treatment response.ConclusionsWe demonstrate for the first time that useful predictors of CD treatment response can be produced from shotgun MGS sequencing of biopsy samples despite the complications related to large proportions of host DNA. The top predictive features that we identified in this study could be useful for building an improved classifier for CD and treatment response based on sufferers' microbiome in the future. The BISCUIT project is funded by a Clinical Academic Fellowship from the Chief Scientist Office (Scotland)-CAF/08/01.
| S-EPMC5769311 | biostudies-literature