关键词： Sulfur-containing metabolites   Cysteine   Taurine   Sulfur metabolome   Fecal metabolome   Inflammatory bowel diseases  

摘要： Sulfur metabolism and sulfur-containing metabolites play an important role in the human digestive system, and sulfur compounds and pathways are associated with inflammatory bowel diseases (IBD). In fact, cysteine metabolism results in the production of taurine and sulfate, and gut microbes catabolize them into hydrogen sulfide, a signaling molecule with various biological functions. Besides metabolites originating from sulfur metabolism, several other sulfur-containing metabolites of different classes were detected in human feces, consisting of non-volatile and volatile compounds. Sulfated steroids and bile acids such as taurine-conjugated bile acids are the major classes along with sulfur amino acids and sulfur-containing peptides. Indeed, sulfurcontaining metabolites were described in stool samples from healthy subjects, patients suffering from colorectal cancer or IBD. In metabolomics-driven studies, around 50 known sulfur-containing metabolites were linked to IBD. Taurine, taurocholic acid, taurochenodeoxycholic acid, methionine, methanethiol and hydrogen sulfide were regularly reported in IBD studies, and most of them were elevated in stool samples from IBD patients. We summarized from this review that there is strong interplay between perturbed gut microbiota in IBD, and the consistently higher abundance of sulfur-containing metabolites, which potentially represent substrates for sulfidogenic bacteria such as Bilophila or Escherichia and promote their growth. These bacteria might shift their metabolism towards the degradation of taurine and cysteine and therefore to a higher hydrogen sulfide production.

关键词： Neuroscience   Stem cells   Medicine/Public Health   general   Psychiatry   Neurosciences   Behavioral Sciences   Pharmacotherapy   Biological Psychology  

摘要： An amendment to this paper has been published and can be accessed via a link at the top of the paper.

关键词： inflammatory bowel disease   colon inflammation   fibrosis   betulinic acid hydroxamate   hypoxia-inducible factor   prolyl hydroxylases   TNBS   DSS  

摘要： Intestinal fibrosis is a common complication of inflammatory bowel disease (IBD) and is defined as an excessive accumulation of scar tissue in the intestinal wall. Intestinal fibrosis occurs in both forms of IBD: ulcerative colitis and Crohn's disease. Small-molecule inhibitors targeting hypoxia-inducing factor (HIF) prolyl-hydroxylases are promising for the development of novel antifibrotic therapies in IBD. Herein, we evaluated the therapeutic efficacy of hydroxamate of betulinic acid (BHA), a hypoxia mimetic derivative of betulinic acid, against IBD in vitro and in vivo. We showed that BAH (5-20 mu M) dose-dependently enhanced collagen gel contraction and activated the HIF pathway in NIH-3T3 fibroblasts;BAH treatment also prevented the loss of trans-epithelial electrical resistance induced by proinflammatory cytokines in Caco-2 cells. In two different murine models (TNBS- and DSS-induced IBD) that cause colon fibrosis, oral administration of BAH (20, 50 mg/kg center dot d, for 17 days) prevented colon inflammation and fibrosis, as detected using immunohistochemistry and qPCR assays. BAH-treated animals showed a significant reduction of fibrotic markers (Tnc, Col1a2, Col3a1, Timp-1, alpha-SMA) and inflammatory markers (F4/80(+), CD3(+), Il-1 beta, Ccl3) in colon tissue, as well as an improvement in epithelial barrier integrity and wound healing. BHA displayed promising oral bioavailability, no significant activity against a panel of 68 potential pharmacological targets and was devoid of genotoxicity and cardiotoxicity. Taken together, our results provide evidence that oral administration of BAH can alleviate colon inflammation and colitis-associated fibrosis, identifying the enhancement of colon barrier integrity as a possible mechanism of action, and providing a solid rationale for additional clinical studies.

关键词： biologics   Crohn's disease   health care charges   parenteral nutrition   short bowel syndrome   teduglutide  

摘要： Background Despite advances in the medical management of inflammatory bowel disease (IBD), a subset of patients may require extensive surgery, leading to short-bowel syndrome/intestinal failure requiring long-term home parenteral nutrition (PN) or customized intravenous fluid (IVF) support. Our aim was to further define the characteristics of IBD patients requiring home PN/IVF. Methods This is an observational study from a prospective IBD research registry. Patients receiving long-term home PN/IVF support during 2009-2015 were identified and compared with remaining IBD patients. Demographics, surgical history, smoking, narcotic use, IBD treatment, healthcare charges, and presence of biomarkers were reviewed. The IBD-PN group was stratified into 3 groups based on median healthcare charges. Results Of 2359 IBD patients, there were 25 (1%, 24 with Crohn's disease) who required home PN/IVF, and 250 randomly selected IBD patients matched for disease type formed the control population. Median duration of PN use was 27 months (interquartile range, 11-66). PN use was significantly associated with smoking, narcotic use, IBD-related operations, and lower quality-of-life scores. Among IBD-PN patients, 7 of 25 (28%, 3 after use of teduglutide) were able to successfully discontinue this modality. Median healthcare charges in the IBD-PN group were $51,456 annually. Median charges in the controls were $3427. Period prevalence mortality was 11.5% in IBD-PN and 3.8% in controls. Conclusions IBD patients requiring long-term home PN/IVF support are a small minority in the present era of immunomodulator/biologic therapy. These refractory patients have a 15-fold increase in annual median healthcare charges compared with control IBD patients.

关键词： Cannabis   Cannabidiol (CBD)   Crohn's disease (CD)   Inflammatory bowel disease (IBD)   Marijuana   Tetrahydrocannabinol (THC)   Ulcerative colitis (UC)  

摘要： Although still not approved at the federal level for medical or adult recreational use, cannabis has been approved in the United States (USA) by individual states for both of these purposes. A total of 15 states now regulate cannabis for adult use and 36 states for medical use. In more recent years, cannabis has gained popularity for the treatment of chronic conditions, inflammatory bowel disease (IBD) being one of them. However, the exact role of cannabis in the treatment of IBD remains uncertain. While cannabis may help in some instances with symptom management, it has not been proven to help with inflammation or to fundamentally correct underlying disease processes. Additionally, along with the perceived symptom benefits of cannabis come concerning issues like dosing inconsistencies, dependence, and cannabinoid hyperemesis syndrome. In this review article, we explore the nuanced relationship between cannabis and the treatment of IBD by summarizing the current research. We also use clinical vignettes to discuss the more practical considerations surrounding its use.

关键词： Anti-TNF   Comparison   IBD   Response to Therapy  

摘要： BACKGROUND & AIMS: Patients with Crohn's disease (CD) or ulcerative colitis (UC) often receive combination therapy with an immunomodulator and tumor necrosis factor antagonists, especially infliximab. However, the benefits of combination therapy with vedolizumab and ustekinumab are unclear. METHODS: We performed a retrospective study of patients with CD or UC initiating vedolizumab or ustekinumab therapy at Massachusetts General Hospital (USA), Alberta Health Sciences (Canada), or Nancy University Hospital (France) with at least 1 year of follow up. The primary outcome was clinical remission or response at week 14, based on the Harvey Bradshaw index for CD or simple clinical colitis index or partial Mayo score for UC. We separately examined week 30 and week 54 clinical outcomes, endoscopic response, and durability of therapy using multivariable regression models and adjusting for relevant confounders. RESULTS: Our study included 549 patients (263 with UC, 286 with CD) receiving maintenance therapy with vedolizumab and 363 patients (4 with UC, 359 with CD) receiving maintenance therapy with ustekinumab with 1 year of follow up. The mean disease duration was 13-15 years. One hundred thirty-one patients receiving vedolizumab (23.9%;78 receiving thiopurine, 53 receiving methotrexate) and 120 patients receiving ustekinumab (33.1%, 57 receiving thiopurine, 63 receiving methotrexate) were receiving combination therapy. For vedolizumab, there was no difference in clinical response or remission with combination therapy vs monotherapy at week 14 (68.2% vs 74.1%;P = .22), week 30 (74.3% vs 75.6%;P = .78) or week 54 (78.3% vs 72.9%, P = .33). For ustekinumab, there was no difference in clinical response or remission with combination therapy vs monotherapy at week 14 (54.6% vs 65.8%;P = .08), week 30 (71.6% vs 77.4%;P = .33) or week 54 (62.1% vs 67.0%;P = .52). There were similar proportions of patients remaining on treatment or with endoscopic response at 1 year among patients

关键词： Anxiety   Depression   Inflammatory bowel disease   Self-compassion   Stress  

摘要： Objective: To date, research with people with inflammatory bowel disease (IBD) has only examined how self compassion is linked with stress, and have exclusively used cross-sectional designs. This study aims to examine the associations of self-compassion with depressive symptoms, anxiety, and stress in people with IBD over time. Methods: Participants were 155 adults with IBD who completed the SCS and the DASS-21 at two different times, spaced 9 months apart. The study design is longitudinal: three separate hierarchical regression models were conducted to examine whether self-compassion at baseline predicted depressive symptoms, anxiety, and stress measured at follow-up, while controlling for the effects of baseline IBD symptomatology and the respective outcome. Results: Participants who had IBD for a longer period of time presented higher levels of self-compassion. Self compassion at baseline predicted lower follow-up levels of depressive symptoms (beta=-0.17, p = 0.015), anxiety (beta=-0.15, p = 0.032), and stress (beta=-0.26, p = 0.001), even in the presence of baseline levels of IBD symptomatology and the outcome. Isolation (as opposed to common humanity) was the most relevant self-compassion component for explaining higher depression levels, while the mindfulness component was important for explaining lower anxiety and stress. Conclusions: This study is the first to demonstrate the prospective effects of self-compassion on mental health indicators in IBD. Given these findings, and previous evidence on the high comorbidity of depression and anxiety and frequent self-report of illness shame and self-criticism in this population, compassion-based interventions may be particularly beneficial for improving well-being in people with IBD.

关键词： Copper   Zinc   Inflammatory bowel disease   Fecal incontinence   National Health and Nutrition Examination Survey  

摘要： The associations between copper and zinc intake with the risk of inflammatory bowel disease (IBD) and fecal incontinence symptoms in the general population are not well understood. This study aims to evaluate the associations of zinc and copper intake with the risk of IBD and fecal incontinence symptoms in adults aged >= 20 years using data from the 2009-2010 National Health and Nutritional Examination Surveys (NHANES) (N= 5593). The presence of IBD was analyzed from the NHANES data, directly querying the presence or absence of ulcerative colitis (UC) and Crohn's disease (CD). Fecal incontinence symptoms including accidental bowel leakage of gas, mucus, liquid, or solid stool were determined by using the bowel health questionnaire. Multivariable logistic regressions models were performed controlling for confounding factors (dietary, lifestyle, psychological, and health conditions). No associations between either zinc or copper intake with IBD were found. However, zinc intake was independently associated with increased risk of bowel leakage of gas or liquid. Compared with quartile 1, the multivariate-adjusted ORs (95%CI) of bowel leakage of gas across quartiles 2-4 of zinc intake were 1.41 (1.15-1.71), 1.30 (1.00-1.68), and 1.61 (1.16-2.23). Likewise, there was a trend for higher odds of bowel leakage of liquid among participants in the higher zinc intake. Compared with quartile 1, the multivariate-adjusted ORs (95%CI) of bowel leakage of liquid across quartiles 2-4 of zinc intake were 3.55 (0.94-13.41), 3.65 (1.27-10.47), and 5.06 (1.25-20.50). Future prospective studies are warranted to confirm these findings.