Symptoms Of Colitis Research Articles

OP20 The effects of upadacitinib on ulcerative colitis symptom resolution and fatigue normalization in patients with moderately to severely active ulcerative colitis: Phase 3 U-ACHIEVE and U-ACCOMPLISH results

Abstract Background Abdominal pain (AP), bowel urgency (BU), stool frequency (SF), rectal bleeding (RB) and fatigue are debilitating symptoms that reduce quality of life in patients with ulcerative colitis (UC). Results from two Phase 3 induction trials and one maintenance trial (U-ACHIEVE [NCT02819635] and U-ACCOMPLISH [NCT03653026]) showed significant and clinically meaningful improvements in these symptoms following induction and maintenance treatment with upadacitinib (UPA) in patients with moderately to severely active UC. We evaluated the effects of 8-week UPA induction and 52-week UPA maintenance treatment on UC symptom resolution, defined as no BU, no AP, and symptomatic remission (no RB, SF≤1), and normalization of fatigue, defined as achievement of a Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT–F) score ≥ 40.1. Methods A total of 988 patients were randomized in the U-ACHIEVE and U-ACCOMPLISH induction studies to receive UPA 45 mg once daily (QD; n=660) or placebo (PBO) QD (n=328). Patients who achieved a clinical response after 8 weeks of induction (n=451) were enrolled in the U-ACHIEVE maintenance study and re-randomised 1:1:1 to UPA 15 mg QD (n=148), UPA 30 mg QD (n=154), or PBO QD (n=149). Symptom resolution was assessed at induction Weeks 0, 2, 4, 6, 8 and maintenance Weeks 0, 4, 8, 12, 20, 28, 36, 44, and 52. A more stringent assessment of symptom resolution and normalization of fatigue was conducted at Weeks 0, 2, and 8 of induction and Weeks 0 and 52 of maintenance. Results A higher percentage of patients achieved symptom resolution during induction treatment as early as Week 2 with UPA 45 mg vs PBO (11.1% vs 0.9%, p <0.001; Figure 1), and sustained through Week 8 (31.2% vs 7.9%, p<0.001). This difference was also observed during maintenance treatment among clinical responders starting at Week 8 with UPA (15 mg: 43.2%; 30 mg: 42.2% vs PBO: 30.2%, p<0.01 and p<0.05, respectively; Figure 2) and sustained through Week 52 (15 mg: 37.2%; 30 mg: 46.1% vs PBO: 12.8%, p<0.001 for both). Furthermore, the percentage of patients who achieved symptom resolution and fatigue normalization was greater with UPA vs PBO at Week 8 of induction (45 mg: 23.4% vs PBO: 6.7%, p <0.001; Figure 3) and Week 52 of maintenance (15 mg: 24.3%; 30 mg: 36.4% vs PBO: 12.1%, p<0.01 and p<0.001, respectively). Conclusion Patients with moderately to severely active UC were more likely to achieve symptom resolution and normalization of fatigue during induction treatment with UPA compared to PBO, and these benefits were sustained during maintenance therapy.

P719 Symptomatic improvement and long-term stability of ulcerative colitis symptoms over 3 years of ozanimod treatment

Abstract Background The phase 3 True North (TN) study demonstrated the efficacy and safety of ozanimod over 52 weeks in patients (pts) with moderately to severely active ulcerative colitis (UC). Pts completing 52 weeks of TN were eligible for the ongoing TN open-label extension (OLE) assessing the long-term efficacy and safety of ozanimod. Presented here is the interim analysis of the TN OLE focused on the symptomatic efficacy of ozanimod in pts with approximately 3 years of continuous ozanimod treatment. Methods Pts who achieved clinical response after receiving 52 weeks of continuous ozanimod during TN and subsequently entered the TN OLE were evaluated (data cutoff: 10 January 2022, at which point the OLE Week 94 disposition was available for pts). Patient-reported (rectal bleeding subscore [RBS] and stool frequency subscore [SFS]) and clinician-reported (Physician’s Global Assessment) symptomatic outcomes were determined. Symptomatic clinical response (partial Mayo score [PMS] ≥1 point and ≥30% reduction in PMS with ≥1-point decrease in RBS or absolute RBS of ≤1) and symptomatic clinical remission (RBS=0 and SFS ≤1 [and decrease of ≥1 point from baseline SFS]) were evaluated at OLE Week 5 through OLE Week 94 (146 weeks of continuous ozanimod treatment) using observed case (OC) and nonresponder imputation (NRI) analyses. PMS, RBS, and SFS were assessed from TN baseline to OLE Week 94. Results In all, 131 pts entered the OLE after achieving clinical response following 52 weeks of continuous ozanimod during TN. At data cutoff, 87.0% completed OLE Week 46 (98 weeks of continuous ozanimod) and 71.8% completed OLE Week 94 (146 weeks of continuous ozanimod). Pts had a mean age of 44 years and 52% were female. Most (68%) had left-sided UC disease, 24% had concomitant corticosteroid use at TN baseline, and 32% had prior exposure to tumor necrosis factor inhibitors. Symptomatic clinical response and symptomatic clinical remission were observed in 100.0% (Figure 1A) and 84.4% (Figure 2A) of pts, respectively, at OLE Week 5 in the OC analysis (93.1% [Figure 1B] and 78.6% [Figure 2B] in the NRI analysis). Rates of symptomatic clinical response and symptomatic clinical remission were maintained through OLE Week 94 in the OC analysis and decreased slightly over time in the NRI analysis. Reductions in mean PMS from baseline were observed during TN and sustained through OLE Week 94. Reductions from TN baseline in RBS (Figure 3) and SFS (Figure 4) were also observed through OLE Week 94. Conclusion This interim analysis of the TN OLE focusing on symptomatic endpoints found that most pts who achieved clinical response after 1 year of ozanimod sustained symptom control for another 2 years.

DOP35 High-fat diet reduces gut microbiota-derived metabolite indole-acetic acid and aggravates colitis

Abstract Background It is widely accepted that high-fat diet (HFD) has been considered as one of the risk factors of inflammatory bowel disease(IBD), while the mechanism is little known. We aimed to examined whether dietary high fat promotes colonic inflammation through modulating gut microbial tryptophan metabolites. Methods The C57BL/6 female mice were fed with chow diet (12kcal% fat) or HFD (60kcal% fat) for 2 weeks. Fresh fecal samples were collected before administration of 2% DSS. LC-MS/MS analysis was performed to detect fecal microbial tryptophan metabolites. Next, 8-week-old mice were administrated 3-indoleacetic acid (IAA) for 7 days prior to 2.5% DSS treatment. The severity of colitis was assessed and the colonic sections were collected. RNA sequencing was performed to analyze the differential genes in intestinal tissue of mice fed with IAA or not. Real-time PCR and Western blotting were performed to detect the transcription and protein expression of mucin sulfation-related genes. High iron diamine-alcian blue (HID-AB) staining of colon tissues and LS174T cells was used to detect the abundance of sulfated mucin. Additionally, the Chromatin immunoprecipitation (ChIP) sequencing is performed to confirm the binding of aryl hydrocarbon receptor(AHR) to 3’-phosphoadenosine 5’-phosphosulfate (PAPS) synthase 2 (PAPSS2). Results Short-term HFD increased the susceptibility to colitis of mice. Mice fed with HFD have impaired tryptophan metabolism with remarkable lower level of IAA. IAA supplementation resulted in ameliorative colitis symptoms. Mechanistically, the transcriptome sequencing detected that IAA supplementation enriched the the cytosolic sulfonation pathway and significantly increased the expression of PAPSS2 of colon tissue, a rate-limiting enzyme on the mucin sulfation pathway. Next, in vivo and in vitro experiments verified IAA increased the expression of PAPSS2 and its downstream genes and promoted the mucin sulfation in golgi apparatus of colon through AHR. ChIP sequencing and ChIP-PCR verified IAA can enhance the binding of AHR to the promoter region of PAPSS2 , which further promoted the expression of PAPS transporter 2 (PAPST2 or Slc35b3) and ultimately promotes the mucin sulfation. Conclusion HFD altered the gut microbial tryptophan metabolites and disrupt the protective effect of IAA on the intestinal barrier. IAA could relief colitis through AHR-PAPSS2-PAPST2-mucin sulfation axis, which may present a potential approach for precise prevention and treatment of IBD.

Sargassum horneri Extract Ameliorates DSS-Induced Colitis through Modulation of mTOR Axis and Intestinal Microbiota

Ulcerative colitis is a chronic inflammatory bowel disease characterized by colonic mucosal inflammation, intestinal microflora imbalance, and intestinal permeability. It is essential to develop natural compounds with anti-inflammatory and intestinal bacterial imbalance correction properties. The brown alga Sargassum horneri is rich in polyphenols, such as fucoxanthin and chromene, which have antioxidant, anti-inflammatory, and anti-cancer properties. In results, S. horneri ethanol extract (SHE) reduced TNF-α and IL-6 levels as well as Pi3k/Mtor/S6k mRNA expression in LPS-treated RAW264.7 and Caco-2 cells. In addition, SHE treatment decreased the expression of genes associated with inflammation and the mTOR axis in the co-culture system while increasing the expression of tight junction factors. In a mouse model of dextran sulfate sodium (DSS)-induced colitis, SHE treatment improved intestinal length, histological scores, and the expression of genes related to tight junctions while decreasing the expression of genes related to inflammatory markers and the mTOR axis. The gut microbiota of mice treated with SHE exhibited a decrease in the ratio of Firmicutes to Bacteroidota, which had been increased by DSS treatment and an increase in beneficial bacteria. Therefore, SHE consumption may be a useful natural alternative, as it improves gut microbiota, alleviates colitis symptoms, and prevents their onset.

PATTERNS OF STEROID USE AMONG A REAL-WORLD NATIONAL COHORT OF VETERANS WITH INFLAMMATORY BOWEL DISEASE

Abstract BACKGROUND Corticosteroids are effective in the acute improvement of symptoms in inflammatory bowel disease (IBD) but are not recommended as maintenance therapy due to lack of long-term efficacy and significant adverse effects. Long term goals for medical management in IBD include achieving steroid-free remission. Biologics such as the anti-tumor necrosis factor alpha Infliximab (IFX) are used to achieve clinical remission, however patterns of continued steroid use among patients on maintenance IFX have not been fully studied. The aim of this study is to evaluate patterns of concomitant steroid use in individuals with IBD on maintenance IFX. METHODS We performed a retrospective cohort study using the national Veteran’s Health Administration dataset. Patients with IBD were identified using a previously validated algorithm of ICD9/10 codes and confirmed by manual chart review. Dispensed medications and demographic data were obtained from VA Corporate Data Warehouse. Patients were eligible for inclusion if they had a confirmed diagnosis of IBD and on maintenance IFX. Maintenance IFX- index date was defined as the first dose of IFX in 2017 with receipt of IFX 7 to 9 weeks before and after IFX-index date. The study period for steroid use was six months prior to and following the IFX-index date. Continued steroid use was defined as two or more filled prescription of oral steroids during the study period. RESULTS There were 642 individuals included who met the criteria outlined above. The majority (594, 92.5%) were male. The racial breakdown was as follows: 516 (80.3%) White, 85 (13.3%) Black, 18 (2.8%) other races, and 23 (3.6%) with unknown race. A total of 402 individuals (62.6%) had ulcerative colitis, 240 individuals (37.4%) had Crohn’s disease. The average age at the IFX-index date was 46.8 (±15.8) years. The average time from initial date of IFX exposure to the Maintenance IFX-index date was 3.6 years. During the study period, 198 (30.9%) patients filled at least one prescription for steroids. 145 of the 198 (73.2%) individuals prescribed had continued steroid use with two or more filled steroid prescriptions, with an average of 3.9 filled prescriptions of steroids during the study period. CONCLUSION While IFX has been shown to be effective in the induction and maintenance of remission in IBD, we observe high rates of continued steroid use in a national cohort of patients with IBD on maintenance IFX. Continued steroid use in patients on IFX maintenance implies inadequate IBD control despite IFX. Further study is required to understand reasons for continued steroid use in order to improve rates of steroid-free remission in IBD.

Salvia miltiorrhiza polysaccharide and its related metabolite 5-methoxyindole-3-carboxaldehyde ameliorate experimental colitis by regulating Nrf2/Keap1 signaling pathway

The roots of Salvia miltiorrhiza have been used in Traditional Chinese Medicine for thousands of years. However, tons of aerial parts of this plant are usually discarded in the production of roots preparation. To make better use of these plant resources, the polysaccharide isolated from the aerial part of S. miltiorrhiza was investigated for its potential protection against intestinal diseases. A pectic polysaccharide (SMAP-1) was isolated and characterized being composed of homogalacturonan as the main chain and rhamnogalacturonan type I as ramified region, with side chains including arabinans and possible arabinogalactan type I and II. SMAP-1 exhibited robust protective effects against dextran sodium sulfate (DSS)-induced colitis and restored colitis symptoms, colonic inflammation, and barrier functions. Anti-oxidative effects were also observed by up-regulating Nrf2/Keap1 signaling pathway. Additionally, the level of serum 5-methoxyindole-3-carboxaldehyde (5-MC) was restored by SMAP-1 identified in metabolomic analysis, being correlated with the aforementioned effects. Protection against oxidative stress on intestinal porcine enterocyte cells (IPEC-J2) by 5-MC was observed through the activation of Nrf2/Keap1 system, as also shown by SMAP-1. In conclusion, SMAP-1 could be a promising candidate for colitis prevention, and 5-MC could be the signal metabolite of SMAP-1 in protecting against oxidative stress in the intestine.

Prunetin alleviates dextran sulfate sodium-induced colitis via the regulation of inflammatory response based on network pharmacology and experimental evidence

Background: Prunetin (Pru), a bioactive flavonoid present in Caulis spatholobi, has been reported to possess a variety of pharmacological effects. However, the therapeutic effect and underlying mechanisms of Pru in inflammatory bowel disease have not been previously investigated. This study aimed to explore the protective action of Pru on dextran sulfate sodium (DSS)-induced colitis by network pharmacology and experimental validation. Methods: The corresponding genes of Pru were predicted using the Comparative Toxicogenomics Database (CTD) and SwissTargetPrediction. Differentially expressed genes (DEGs) between the control rats and DSS-induced colitis rats were identified from the microarray profile GSE54005. Cytoscape software was used to visualize the protein–protein interaction (PPI) networks of overlapped targets. Besides, an animal experiment was performed to verify the therapeutic effect of Pru on colitis. Results: 21 potential targets related to colitis treated by Pru were identified. The topological analysis revealed that Tnf, Il6, and Il1b were the key genes. The KEGG and GO enrichment analyses showed that key targets were enriched in the inflammatory bowel disease, IL-17 signaling pathway, TNF signaling pathway, regulation of inflammatory response, and acute inflammatory response. The in vivo experiment revealed that Pru improves pathological injury and alleviated colitis symptoms via the regulation of Tnf, Il6, and Il1b, which were involved in the acute inflammatory response. Conclusion: Our findings demonstrated that Pru alleviates colitis symptoms through the regulation of inflammatory response, which provides a scientific basis for Pru in preventing and treating colitis.

Are heat-killed probiotics more effective than live ones on colon length shortness, disease activity index, and the histological score of an inflammatory bowel disease-induced murine model? A meta-analysis.

This study was conducted to compare the efficiency of heat-killed and live probiotics against colon length shortness, disease activity index (DAI), and the histological score of an inflammatory bowel disease (IBD) via a meta-analysis. In February 2022, the eligible papers were collected from four databases (Google Scholar, PubMed, ScienceDirect, and Scopus). Using common- and random-effects models, the effect sizes were estimated throughout the standardized mean difference. Forty-three papers were recorded for our meta-analysis, and the heterogeneity of the effect sizes was determined with Cochran's Q test, followed by meta-ANOVA and meta-regression analyses. The probiotics (live and heat-killed) had globally an improving or preventive effect on colon length shortness, DAI, and histological score. The sub-group analysis revealed that the heat-killed probiotics had statistically (P>.05) the same improving effect on colon length shortness, DAI, and histological score as live probiotics. In conclusion, this study suggested that live and heat-killed probiotics had a similar impact on IBD symptoms investigated in this study. The present outcomes would be a good base for researchers willing to further compare the effects of live and heat-killed probiotics on IBD.

Folic acid-modified lactoferrin nanoparticles coated with a laminarin layer loaded curcumin with dual-targeting for ulcerative colitis treatment

Curcumin (CUR) is a promising natural compound in ulcerative colitis (UC) treatment, but limited by its low oral bioavailability and poor targeting ability. Therefore, given the targeting action of lactoferrin (LF) by binding to the LF receptors of intestinal epithelial cells (IECs) and of folic acid (FA) by binding to the FA receptors of macrophages, we developed an oral dual-targeting nanosystem. Laminarin (LA)-coated, FA-modified LF nanoparticles (NPs) were used to encapsulate CUR (LA/FA/CUR-NPs) with a food-grade, enzyme-sensitive, and dual-targeting capacity. For the generated NPs, LF improved the loading efficiency of CUR (95.08 %). The LA layer could improve the upper gastrointestinal tract stability of the NPs while improve drug release around colon lesion through β-glucanase digestion. Based on the cellular uptake evaluation, FA/CUR-NPs were capable of specifically targeting colonic epithelial cells and macrophages through LF and FA ligands, respectively, to enhance the uptake efficiency. Moreover, based on the advantage of the dual-targeting strategy, oral administration of FA/CUR-NPs obviously reduced colitis symptoms by alleviating inflammation, accelerating colonic mucosal barrier repair and restoring the balance of the intestinal microbiota. This dual-targeted nanodesign corresponded to the multi-bioresponsibilities of CUR, thus offering a promising approach in UC treatment.

Modified Gegen Qinlian decoction ameliorates DSS-induced chronic colitis in mice by restoring the intestinal mucus barrier and inhibiting the activation of γδT17 cells

BackgroundCurrent therapeutics for ulcerative colitis (UC) have limitations. Classical Formula Gegen Qinlian decoction (GQD) is derived from Shang Han Lun and has a long history of treating gastrointestinal diseases such as diarrhea and UC. Nevertheless, the exact mechanism of it needs to be further clarified. PurposeWe aimed to investigate the treatment effects of modified GQD (MGQD) on dextran sodium sulfate (DSS)-induced chronic colitis in mice and conduct further exploration of its underlying mechanisms. MethodsThe protective effect of MGQD was estimated in a DSS-induced chronic colitis mouse model. Model evaluation included body weight, disease activity index (DAI) score, colon length and histopathology. Alcian Blue/Phosphoric Acid Schiff (AB/PAS) staining, transmission electron microscopy (TEM), immunofluorescence and real time‒PCR (RT-PCR) were used to assess goblet cell function. ELISA, flow cytometry and immunofluorescence were applied to estimate the immunoinflammatory status. Western blot was performed to test the protein expression levels of relevant pathways and related receptors. All experiments were conducted in duplicate. ResultsMGQD alleviated DSS‑induced chronic colitis symptoms in mice, protected goblet cell function and restored the intestinal mucus barrier. Furthermore, MGQD efficiently suppressed the abnormal immune inflammatory response and the activate of γδT17 cells and NLRP3 inflammasome. ConclusionThe mechanisms by which MGQD protects against DSS-induced chronic colitis may involve restoring goblet cell function, repairing the intestinal mucus barrier, and modulating the immune inflammatory response. More importantly, MGQD inhibited NLRP3 inflammasome-associated signaling pathway activation, which consequently reduced the activation of γδT17 cells.

Gut Bacterial Indole-3-acetic Acid Induced Immune Promotion Mediates Preventive Effects of Fu Brick Tea Polyphenols on Experimental Colitis

Ulcerative colitis has been consistently associated with gut microbiota imbalance and disturbed immune system. Emerging research suggests a protective function of polyphenols on prevention and treatment of ulcerative colitis, yet underlying mechanisms remain unclear. Fu brick tea, a postfermented tea, contains abundant polyphenols with anti-inflammatory and antioxidant properties. In the present study, we found that prophylactic supplementation of polyphenols extracted from Fu brick tea (FBTP) dose-dependently alleviated colitis symptoms, immune cells infiltration, and pro-inflammatory cytokines secretion in mice suffering dextran sulfate sodium induced murine colitis. FBTP substantially reshaped gut microbiota and promoted microbial transformation of tryptophan into indole-3-acetic acid (I3A), thereafter leading to aryl hydrocarbon receptor (AHR)-mediated protection from colitis through enhanced expressions of IL-22 and tight junction proteins (i.e., ZO-1, occluding and claudin-1) in colon. Multiomics integration analyses revealed strong connections between I3A, tryptophan-metabolizing bacteria, AHR activity, and pathological phenotypes of colitis. Notably, FBTP failed to significantly alleviate colitis symptoms in the absence of gut microbiota, while intragastric administration of I3A could imitate benefits of FBTP on colitis alleviation and intestinal epithelial homeostasis through a direct enhancement in AHR activity in microbiota-depleted mice. These findings further determine the key role of gut microbiota controlled I3A-AHR signaling in mediating the FBTP on colitis alleviation. This study provides the first data proposing the FBTP as a natural prebiotic for colitis alleviation through the gut microbiota-dependent modulation of the AHR pathway. Most importantly, we also identified I3A as a key microbial metabolite targeted by FBTP for exhibiting health-promoting effects.

Soy protein isolate-polyguluronate nanoparticles loaded with resveratrol for effective treatment of colitis

Polyguluronate (PG) is an acidic homopolymer of α-(1,4)-l-guluronate separated from alginate. In this study, PG was first grafted with soy protein isolate (SPI) through the Maillard reaction to obtain a new glycoprotein (SPI-PG). Then, this novel glycoprotein was used to prepare nanoparticles to encapsulate the resveratrol (RES). Our results showed that SPI-PG-RES had better pH stability, storage stability and ionic stability than SPI-RES. In vitro digestion experiments showed that the RES bioavailability of SPI-PG-RES was much higher than that of free RES and SPI-RES. Furthermore, the in vitro antioxidant capacity of SPI-PG-RES was much stronger than that of free RES and SPI-RES. In addition, SPI-PG-RES was more effective in preventing the symptoms of DSS-induced colitis than RES and SPI-RES. These results suggested that the protein nanoparticles prepared using SPI-PG were a stable and effective hydrophobic polyphenol carrier and could be applied to food-grade components in functional foods and nutritional supplements.

Corylin ameliorates chronic ulcerative colitis via regulating the gut–brain axis and promoting 5-hydroxytryptophan production in the colon

BackgroundChronic ulcerative colitis (UC) is a lifelong disease, patients with chronic UC have a high prevalence of common mental disorders. The increasing interest in the role of gut-brain axis is seen in inflammatory bowel diseases. PurposeCorylin is a representative flavonoid compound isolated from the Psoraleae Fructus. This study aimed to identify the effects and mechanism of corylin on the inflammation interactions and 5-HT synthesis between the gut and brain in chronic UC. MethodsDextran sulfate sodium (DSS) induced chronic UC mouse model was established to assess the therapeutic effect of corylin on chronic UC symptoms. The expression of inflammatory cytokines was detected in the colon and brain. The expression of tight junction (TJ) proteins of intestinal mucosal barrier and blood–brain barrier (BBB) and the ionized calcium-binding adaptor molecule 1 (Iba1) in the hippocampus were determined by western blotting and immunofluorescence staining. In addition, several tryptophan (Trp) metabolites and related neurotransmitters in faeces, colon, serum, and brain were detected by UPLC-MS/MS. The interaction between corylin and 5-hydroxytryptophan decarboxylase (5-HTPDC) was performed by molecular docking and surface plasmon resonance (SPR). Finally, the changes of gut microbiota composition were analyzed by 16S rRNA sequencing. ResultsCorylin significantly alleviated colitis symptoms and inhibited inflammatory response in the colon and brain of DSS-induced chronic UC mice. The TJ proteins of intestinal mucosal barrier and BBB were improved and the expression of Iba1 in the hippocampus was normalized after corylin treatment. In addition, corylin treatment increased the expression of neurotransmitters in the brain, especially 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP), but the expression of 5-HT in the colon was inhibited. Further study firstly proved that corylin could bind to the 5-HTDPC, and then inhibit the expression of 5-HTDPC and VB6, resulting in the 5-HT reduction and 5-HTP accumulation in the colon. Moreover, the intake of corylin transformed the diversity and composition of intestinal microbiota, Bacteroides, Escherichia-Shigella, and Turicibacter were decreased but Dubosiella, Enterorhabdus, and Candidatus_Stoquefichus were increased. ConclusionCorylin administration ameliorated DSS-induced colitis and inhibited intestinal inflammation and neuroinflammation via regulating the inflammation interactions across gut-brain axis and increasing 5-HTP generation in the colon.

Bifidobacterium longum CCFM1206 Promotes the Biotransformation of Glucoraphanin to Sulforaphane That Contributes to Amelioration of Dextran-Sulfate-Sodium-Induced Colitis in Mice.

Glucoraphanin, rich in broccoli seed extract (BSE), is generally inert but can be biotransformed into active sulforaphane by gut bacteria. This study aimed to screen probiotics with glucoraphanin-metabolizing ability and explore the effect of a combination of strain and BSE on colitis induced by dextran sulfate sodium (DSS) in mice. Bifidobacterium longum CCFM1206 was isolated from healthy adult feces. Ultra-high-performance liquid chromatography Q Exactive mass spectrometry analysis revealed the presence of sulforaphane, sulforaphane-l-cysteine, and erucin in the BSE supernatant fermented by B. longum CCFM1206 in vitro. Combined and individual interventions of BSE and B. longum CCFM1206 were applied to explore the effects on DSS-induced colitis. The results suggested that the combination of B. longum CCFM1206 and BSE could ameliorate colitis symptoms, relieve colonic inflammatory reactions and oxidative stress, and protect the intestinal barrier in DSS-induced mice. In comparison to the BSE intervention alone, the combined intervention of B. longum CCFM1206 and BSE promoted the generation of sulforaphane and sulforaphane-N-acetylcysteine in mice colon from 220.88 ± 19.81 to 333.99 ± 36.46 nmol/g and from 232.04 ± 26.48 to 297.50 ± 40.08 nmol/g dry weight feces, respectively. According to quantitative reverse transcription polymerase chain reaction and immunohistochemical analysis, B. longum CCFM1206 and BSE effectively activated the transcription and expression of genes related to the Nrf2 signaling pathway. These results were intended to elucidate that probiotics could elevate the bioactivity of dietary phytochemicals in vivo, and the combination had potential for therapeutic treatment of colitis.

A Comparison of the Effects of COVID-19 on Irritable Bowel Syndrome and Inflammatory Bowel Disease Patients While Working at Home and in the Office: A Retrospective Study.

Background Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) have a strong relationship with psychological stress. Studies have shown increased stress levels in patients with IBS and IBD during the SARS-CoV-2 (COVID-19) pandemic. The current literature on the impact ofwork environment on IBD and IBS symptoms is limited, particularly during the current pandemic. Objective This study aims to analyze how the pandemic impacted patients with IBS and IBD in the setting of staying home versus working outside the home. Methods After Institutional Review Board (IRB) approval, a retrospective review of 245 patients with IBS and IBD who followed with our gastroenterology clinic in the past year was performed. Patients were asked about symptoms including, but not limited to, worsening diarrhea, constipation, and abdominal pain. Pearson's chi-squared test was used for analysis. Results Of the 245 patients in our study, 67 had IBS, 166 had IBD, and 12 had both. The male-to-female ratio was 1:1.4. A total of 136 (55.5%) patients worked from home during the pandemic, while 109 (44.5%)patients worked outside. Eighty-three patients working from home reported no change in symptoms, 35 reported worsening symptoms, and18 reported an improvement in symptoms. Sixty-eight patients working outside the home reported no change in symptoms, 26 reported worsening symptoms, and 15 reported improvements. Working outside the home had a statistically significant relationship with COVID-19 infection. Thirty patients were infected, of which 22 (73.3%) worked outside the home (p=0.01). Overall, 203(82.8%) patients received the vaccine, and only 14 of these patients reported worsening gastrointestinal (GI) symptoms one week after receiving the vaccine. Comparable results were seen after dividing the data into cohorts of IBS and IBD patients. Of the patients with IBD staying at home,15.9% had depression (p=0.01). Conclusion Most patients had symptoms at baseline. There was no statistically significant correlation between change in symptoms and work settings. Patients were less likely to be infected with COVID-19 while staying home. Our patient population showed a high vaccination rate of 82.9% as compared to the national average of 59.2% (source: Centers for Disease Control and Prevention (CDC)). Only 5.7% of the patients reported new or worsening gastrointestinalsymptoms in the week following vaccination. The limitations of the study included its retrospective design and poor correlation in general between symptoms and disease activity in IBD patients.

Lifestyle Factors and Silent Inflammatory Bowel Disease

Introduction: Hypoalgesic or silent inflammatory bowel disease (IBD) is a poorly understood condition that has been associated with poor clinical outcomes. There is evidence that lifestyle factors, including diet, exercise, and substance use can influence inflammatory activity and symptoms in IBD. It is unclear, though, whether these issues impact pain experience in IBD. We performed this study to evaluate the potential relationship between several key lifestyle factors and silent IBD. Methods: We performed a retrospective analysis using an IBD natural history registry based in a single tertiary care referral center. We compared demographic and clinical features in 2 patient cohorts defined using data from simultaneous pain surveys and ileocolonoscopy: (a) active IBD without pain (silent IBD) and (b) active IBD with pain. We also evaluated the relative incidence of characteristics related to diet, exercise, sexual activity, and substance abuse. Results: One hundred and eighty IBD patients had active disease and 69 (38.3%) exhibited silent IBD. Silent IBD patients exhibited incidences of disease type, location, and severity as pain-perceiving IBD patients. Silent IBD patients were more likely to be male and less likely to exhibit anxiety and/or depression or to use cannabis, analgesic medication, or corticosteroids. There were no significant differences in dietary, exercise-related, or sexual activities between silent and pain-perceiving IBD patients. Conclusions: Silent IBD was associated with reduced incidence of substance and analgesic medication use. No relationships were found between silent IBD and diet, exercise, or sexual activity, though specific elements of each require further dedicated study.

Agreement Level of Inflammatory Bowel Disease Symptom Reports between Children and Their Parents.

Children with inflammatory bowel disease (IBD) frequently undergo clinical assessments, involving triadic communication between clinician, parent, and child. During such encounters parents are traditionally the main communicator of information on their child's IBD, including subjective symptom reports. The level of agreement between children and their parents for IBD symptoms is poorly understood, and this study aimed to examine this factor. This was a cross-sectional study among children with IBD, and one parent. A validated paediatric IBD symptom report tool (IBDnow) enabled children and their parent to rate seven pain, well-being, and stool metrics, with dyads completing the tool concurrently. Results were assessed using: Individual agreement: proportion of identical symptom reports by each dyad (ideal score >0.7); Category agreement: percentage of identical reports for IBDnow metrics for the cohort; Inter-rater reliability: Gwet's AC1 coefficient with higher scores indicating better reliability (maximum=1). Seventy-four parent/child dyads participated; child's mean age 12.2 years (standard deviation [SD] 2.9, range 6-16), mean time since diagnosis 2.8 years (SD 3), 54% female, 73% had Crohn's Disease. Mean individual agreement level was 0.6, with 27% of dyads agreeing on ≥6/7 IBDnow metrics. Category agreement was reported by 61% of dyads, 20% of parents overestimated, and 19% underestimated, their child's symptoms. Inter-rater reliability ranged from fair to good. These results should improve clinician awareness of how IBD symptom reports from parents may introduce bias. Children should be considered the most important source of symptom reports, and tools such as IBDnow utilised to enhance communication.

Plant-derived exosomal nanoparticles: potential therapeutic for inflammatory bowel disease.

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is a chronic autoimmune disorder characterized by inflammation. However, currently available disease-modifying anti-IBD drugs exhibit limited efficacy in IBD therapy. Furthermore, existing therapeutic approaches provide only partial relief from IBD symptoms and are associated with certain side effects. In recent years, a novel category of nanoscale membrane vesicles, known as plant-derived exosome-like nanoparticles (PDENs), has been identified in edible plants. These PDENs are abundant in bioactive lipids, proteins, microRNAs, and other pharmacologically active compounds. Notably, PDENs possess immunomodulatory, antitumor, regenerative, and anti-inflammatory properties, making them particularly promising for the treatment of intestinal diseases. Moreover, PDENs can be engineered as targeted delivery systems for the efficient transport of chemical or nucleic acid drugs to the site of intestinal inflammation. In the present study, we provided an overview of PDENs, including their biogenesis, extraction, purification, and construction strategies, and elucidated their physiological functions and therapeutic effects on IBD. Additionally, we summarized the applications and potential of PDENs in IBD treatment while highlighting the future directions and challenges in the field of emerging nanotherapeutics for IBD therapy.

Lactobacillus Acidophilus Regulates the Expression of MicroRNAs and Ameliorates the Symptoms of Acid-induced Ulcerative Colitis in Rats

Lactobacillus Acidophilus Regulates the Expression of MicroRNAs and Ameliorates the Symptoms of Acid-induced Ulcerative Colitis in Rats

Change in Urgency Status Among Ulcerative Colitis Patients: Understanding a Potential Unmet Patient Need From the CorEvitas Inflammatory Bowel Disease Registry.

Fecal urgency is a common symptom of Ulcerative Colitis (UC). We explored the association between changes in fecal urgency for patient characteristics and evaluated the association between change in treatment and change in fecal urgency. The study cohort (n= 400) included UC patients in the CorEvitas Inflammatory Bowel Disease Registry between May 3, 2017 and September 1, 2020. Fecal urgency was defined using the Simple Clinical Colitis Activity Index. Urgency groups were formed by urgency at enrollment and 6-month follow-up visit: no persistent urgency at both visits (NPU); change from urgency to no urgency (UN); change from no urgency to urgency (NU); and persistent urgency at both visits (PU). Descriptive statistics were used to explore between urgency group differences at baseline and Kaplan-Meier curves to compare time to first treatment change. Groups included NPU (n= 175), UN (n= 86), NU (n= 56), and PU (n= 83). At enrollment, we found differences between groups for increased depression, anxiety, prior infections, diabetes; also, greater fatigue, pain, work impairment, work hours affected, and daily activities impacted. Compared to NPU patients, UN, NU, and PU patients were more likely to change treatment between enrollment and 6-month follow-up visit, and a higher proportion of UN, NU, and PU patients on a biologic at enrollment changed treatment vs the NPU group between both visits. Among real-world UC patients, fecal urgency status is associated with increased comorbidities and worse patient-reported outcomes and significant differences in change of treatment and time to treatment change. Urgency at any time point diminishes quality of life and may be a sign of inadequate therapy, which often is an indication to switch therapy.