Effects of electroacupuncture with "intestinal disease prescription" on NLRP3 inflammasome and intestinal mucosal barrier in rats with acute ulcerative colitis. / 电针"è‚ ç— æ–¹"å¯¹æ€¥æ€§æºƒç–¡æ€§ç»“è‚ ç‚Žå¤§é¼ NLRP3ç‚Žæ€§å°ä½“å’Œè‚ é»è†œå±éšœçš„å½±å“.

OBJECTIVES: To observe the effects of electroacupuncture (EA) with "intestinal disease prescription" on the intestinal mucosal barrier and NLRP3 inflammasome in rats with dextran sulfate sodium (DSS)-induced acute ulcerative colitis (UC), and explore the underlying mechanism of EA with "intestinal disease prescription" for the treatment of UC. METHODS: Thirty-two healthy male SPF-grade SD rats were randomly divided into a blank group, a model group, a medication group, and an EA group, with 8 rats in each group. Except for the blank group, the UC model was established by administering 5% DSS solution for 7 days. After modeling, the rats in the medication group were treated with mesalazine suspension (200 mg/kg) by gavage, while the rats in the EA group were treated with acupuncture at bilateral "Tianshu" (ST 25), "Shangjuxu" (ST 37) and "Zhongwan" (CV 12), with the ipsilateral "Tianshu" (ST 25) and "Shangjuxu" (ST 37) connected to the electrodes of the EA instrument, using disperse-dense wave, with a frequency of 10 Hz/50 Hz, and each intervention lasted for 20 minutes. Both interventions were performed once daily for 3 days. The general conditions of rats were observed daily. After intervention, the disease activity index (DAI) score was calculated; colon tissue morphology was observed using HE staining; serum levels of pro-inflammatory cytokines (interleukin [IL]-18, IL-1ß) were measured by ELISA; protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 in colon tissues was detected by Western blot; positive expression of zonula occludens-1 (ZO-1) and Occludin in colon tissues was examined by immunofluorescence. RESULTS: Compared with the blank group, the rats in the model group exhibited poor general conditions, slow body weight gain, shortened colon length (P<0.01), increased DAI score and spleen index (P<0.01), elevated serum IL-18 and IL-1ß levels, and increased protein expression of NLRP3, ASC, and Caspase-1 in colon tissues (P<0.01), along with decreased positive expression of ZO-1 and Occludin in colon tissues (P<0.01). Compared with the model group, the rats in the medication group and the EA group exhibited improved general conditions, accelerated body weight gain, increased colon length (P<0.05), reduced DAI scores and spleen indexes (P<0.05), decreased serum IL-18 and IL-1ß levels, and lower protein expression of NLRP3, ASC and Caspase-1 in colon tissues (P<0.05), as well as increased positive expression of ZO-1 and Occludin in colon tissues (P<0.05). There were no significant differences in the above indexes between the medication group and the EA group (P>0.05). Compared with the blank group, the rats in the model group exhibited disrupted colon mucosal morphology, disordered gland arrangement, and atrophy of crypts, along with significant inflammatory cell infiltration. Compared with the model group, the rats in both the medication group and the EA group showed relatively intact colon mucosal morphology, with restored and improved gland and crypt structures, and reduced inflammatory cell infiltration. CONCLUSIONS: EA with "intestinal disease prescription" has a significant therapeutic effect on DSS-induced UC, possibly by regulating the expression of NLRP3 inflammasome and proteins related to the intestinal mucosal barrier, thereby alleviating symptoms of ulcerative colitis.

Short-chain fatty acid-producing bacterial strains attenuate experimental ulcerative colitis by promoting M2 macrophage polarization via JAK/STAT3/FOXO3 axis inactivation.

BACKGROUND: Patients with inflammatory bowel disease (IBD), dysbiosis, and immunosuppression who receive fecal microbiota transplantation (FMT) from healthy donors are at an increased risk of developing bacteremia. This study investigates the efficacy of a mixture of seven short-chain fatty acid (SCFA)-producing bacterial strains (7-mix), the resulting culture supernatant mixture (mix-sup), and FMT for treating experimental ulcerative colitis (UC) and evaluates underlying mechanisms. METHODS: Utilizing culturomics, we isolated and cultured SCFA-producing bacteria from the stool of healthy donors. We used a mouse model of acute UC induced by dextran sulfate sodium (DSS) to assess the effects of 7-mix, mix-sup, and FMT on intestinal inflammation and barrier function, microbial abundance and diversity, and gut macrophage polarization by flow cytometry, immunohistochemistry, 16S rRNA gene sequencing, and transwell assays. RESULTS: The abundance of several SCFA-producing bacterial taxa decreased in patients with UC. Seven-mix and mix-sup suppressed the inflammatory response and enhanced intestinal mucosal barrier function in the mouse model of UC to an extent similar to or superior to that of FMT. Moreover, 7-mix and mix-sup increased the abundance of SCFA-producing bacteria and SCFA concentrations in colitic mice. The effects of these interventions on the inflammatory response and gut barrier function were mediated by JAK/STAT3/FOXO3 axis inactivation in macrophages by inducing M2 macrophage polarization in vivo and in vitro. CONCLUSIONS: Our approach provides new opportunities to rationally harness live gut probiotic strains and metabolites to reduce intestinal inflammation, restore gut microbial composition, and expedite the development of safe and effective treatments for IBD.

Defining predictors of responsiveness to advanced therapies in Crohn's disease and ulcerative colitis: protocol for the IBD-RESPONSE and nested CD-metaRESPONSE prospective, multicentre, observational cohort study in precision medicine.

INTRODUCTION: Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient's quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients.Current understanding of IBD pathogenesis implicates complex interactions between host genetics and the gut microbiome. Most cohorts studying the gut microbiota to date have been underpowered, examined single treatments and produced heterogeneous results. Lack of cross-treatment comparisons and well-powered independent replication cohorts hampers the ability to infer real-world utility of predictive signatures.IBD-RESPONSE will use multi-omic data to create a predictive tool for treatment response. Future patient benefit may include development of biomarker-based treatment stratification or manipulation of intestinal microbial targets. IBD-RESPONSE and downstream studies have the potential to improve quality of life, reduce patient risk and reduce expenditure on ineffective treatments. METHODS AND ANALYSIS: This prospective, multicentre, observational study will identify and validate a predictive model for response to advanced IBD therapies, incorporating gut microbiome, metabolome, single-cell transcriptome, human genome, dietary and clinical data. 1325 participants commencing advanced therapies will be recruited from ~40 UK sites. Data will be collected at baseline, week 14 and week 54. The primary outcome is week 14 clinical response. Secondary outcomes include clinical remission, loss of response in week 14 responders, corticosteroid-free response/remission, time to treatment escalation and change in patient-reported outcome measures. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Wales Research Ethics Committee 5 (ref: 21/WA/0228). Recruitment is ongoing. Following study completion, results will be submitted for publication in peer-reviewed journals and presented at scientific meetings. Publications will be summarised at www.ibd-response.co.uk. TRIAL REGISTRATION NUMBER: ISRCTN96296121.

Inflammatory Bowel Disease in Adults - Experience and Challenges in Gastroenterology Practices in Calabar, South-South Nigeria.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that is reported to be rare in Africans. The objective of this study is to share the experience of our Gastroenterology practice in Calabar, Cross River State on IBD. METHODS: This is a ten-year review of the records of patients visiting the Gastroenterology clinic of the University of Calabar Teaching Hospital and two private gastroenterology clinics in Calabar Municipality. The diagnosis of IBD was made based on clinical, laboratory, endoscopic, and histological data obtained. RESULTS: Eight patients presented with features consistent with IBD. Six had ulcerative colitis while 2 had Crohn's disease. Seven patients had moderate disease with the main clinical features being recurrent mucoid bloody diarrhoea. All the patients had treatments with either sulphasalazine or mesalazine as well as azathioprine, steroids and antibiotics with variable response. One patient had strictures requiring a colostomy, while another developed colorectal cancer as complications of IBD. CONCLUSION: Although IBD is uncommon in Nigeria, a high index of suspicion is important, especially in patients presenting with the recurrent passage of mucoid bloody stools. Hence, the role of colonoscopy and histology are invaluable in establishing the diagnosis.

FONDEMENT: La maladie inflammatoire de l'intestin (MII) est un trouble inflammatoire chronique du tractus gastro-intestinal qui est rapporté comme étant rare chez les Africains. L'objectif de cette étude est de partager l'expérience de notre pratique en gastroentérologie à Calabar, dans l'État de Cross River, sur la MII. MÉTHODES: Il s'agit d'une revue de dix ans des dossiers des patients fréquentant la clinique de gastro-entérologie de l'Hôpital universitaire de Calabar et de deux cliniques privées de gastroentérologie dans la municipalité de Calabar. Le diagnostic de MII a été posé sur la base de données cliniques, biologiques, endoscopiques et histologiques obtenues. RÉSULTATS: Huit patients présentaient des caractéristiques compatibles avec la MII. Six présentaient une colite ulcéreuse tandis que 2 présentaient une maladie de Crohn. Sept patients avaient une maladie modérée avec comme principale caractéristique clinique des diarrhées muqueuses sanglantes récurrentes. Tous les patients ont été traités soit avec de la sulfasalazine soit avec de la mésalazine ainsi que de l'azathioprine, des stéroïdes et des antibiotiques avec une réponse variable. Un patient avait des sténoses nécessitant une colostomie, tandis qu'un autre développait un cancer colorectal comme complications de la MII. CONCLUSION: Bien que la MII soit rare au Nigeria, un indice de suspicion élevé est important, surtout chez les patients présentant un passage récurrent de selles muqueuses sanglantes. Ainsi, le rôle de la coloscopie et de l'histologie est inestimable pour établir le diagnostic. MOTS-CLÉS: Adultes, Maladie de Crohn, Maladie inflammatoire de l'intestin, Colite ulcéreuse.

Microbiota therapeutics for inflammatory bowel disease: the way forward.

Microbiota therapeutics that transplant faecal material from healthy donors to people with mild-to-moderate ulcerative colitis have shown the potential to induce remission in about 30% of participants in small, phase 2 clinical trials. Despite this substantial achievement, the field needs to leverage the insights gained from these trials and progress towards phase 3 clinical trials and drug approval, while identifying the distinct clinical niche for this new therapeutic modality within inflammatory bowel disease (IBD) therapeutics. We describe the lessons that can be learned from past studies of microbiota therapeutics, from full spectrum donor stool to defined products manufactured in vitro. We explore the actionable insights these lessons provide on the design of near-term studies and future trajectories for the integration of microbiota therapeutics in the treatment of IBD. If successful, microbiota therapeutics will provide a powerful orthogonal approach (complementing or in combination with existing immunomodulatory drugs) to raise the therapeutic ceiling for the many non-responders and partial responders within the IBD patient population.

Perceptions, behaviours and barriers towards exercise practices in inflammatory bowel disease.

Inflammatory bowel disease (IBD), a chronic disease affecting the digestive tract, has a significant impact on health-related quality of life. Pharmaceutical treatment is typically adopted, yet exercise is increasingly becoming recognized as an adjunct therapy. This study aimed to explore the perspectives, behaviours, and barriers of IBD patients in terms of their exercise habits. A 16-item closed-ended questionnaire was completed by 463 adult IBD patients (Ulcerative colitis = 57.02%, Crohn's dis-ease = 40.60% and Other = 2.38%) (Female = 76.67%, Male = 22.46 and Non-binary = 0.86%). The questionnaire was divided into three sections: baseline/demographic characteristics, disease characteristics, and exercise perceptions, beliefs, and behaviours. Significantly (P<0.001) more participants (63.07%) reported that they engage regularly with exercise compared to those who do not; however, engagement was significantly lower in female patients (59.72%) compared to males (74.04%). Respondents also rated significantly (P<0.001) that a combination of factors prevents engagement in exercise (74.30%). Moderate intensity exercise was the predominant (P<0.001) aerobic modality (39.04%), the majority (P<0.001) response was that patients undertake no resistance training (27.74%), and significantly more (P<0.001) patients indicated that they don't know whether resistance training can influence IBD either positively (57.53%) or negatively (62.33%). Whilst it is encouraging that IBD patients are engaging regularly with exercise, the reduced levels of engagement in females and lack of knowledge/ engagement with resistance training, indicate that future implementation and educational developments are necessary to enhance exercise in females and resistance training engagement in all IBD patients.

Efficacy and safety of moxibustion for ulcerative colitis: protocol for a systematic review and meta-analysis.

INTRODUCTION: Ulcerative colitis (UC) is a global chronic inflammatory bowel disease, and the poor efficacy of currently available pharmacological regimens makes the management of UC a great challenge. Moxibustion has shown great potential in the management of UC. However, its effectiveness and safety are still controversial. The purpose of this study is to synthesise the latest evidence regarding the clinical efficacy and safety of moxibustion for UC. METHODS AND ANALYSIS: The Cochrane Library, PubMed, EMBASE, CNKI, Wanfang, VIP and SinoMed databases will be searched from inception to July 2023, to identify all randomised controlled trials with moxibustion for UC. The primary outcome will be clinical efficacy, as measured by validated scales. The serum inflammatory factor, colonoscopy results, quality of life, recurrence rate and adverse events will be the secondary outcomes. The Cochrane Risk of Bias 2.0 tool will be used to assess the methodological quality of each included trial. All data extraction will be carried out independently by two investigators. RevMan V.5.4 software will be used for data analysis and Cochran's Q statistic and I2 test will be used to assess heterogeneity between studies. In addition, we will perform subgroup analyses, sensitivity analyses and publication bias if the available data are sufficient. The strength of evidence will be graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. ETHICS AND DISSEMINATION: Ethics approval is not required for this review. Our findings will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023425481.

Histologic assessments in ulcerative colitis: the evidence behind a new endpoint in clinical trials.

INTRODUCTION: Treatment goals for ulcerative colitis (UC) are evolving from the achievement of clinical remission to more rigorous goals defined by endoscopic and histologic healing. Achievement of deeper remission targets aims to reduce the risk of colectomy, hospitalizations, and colorectal cancer. AREAS COVERED: This review covers histologic assessments, histologic remission as a clinical trial endpoint, and the association between histologic disease activity and clinical outcomes. Future directions are also discussed, including the use of advanced imaging and artificial intelligence technologies, as well as potential future treatment targets beyond histologic remission. EXPERT OPINION: Histologic assessments are used for their sensitivity in measuring mucosal inflammatory changes in UC. Due to correlation with disease activity, histologic assessments may support clinical decision-making regarding treatment decisions as such assessments can be associated with rates of clinical relapse, hospitalization, colectomy, and neoplasia. While histologic remission is limited by varying definitions and multiple histologic indices, work is ongoing to create a consensus on the use of histologic assessments in clinical trials. As research advances, aspirational targets beyond histologic remission, such as molecular healing and disease clearance, are being explored.

Ulcerative colitis (UC) is the most common inflammatory bowel disease and often results in bloody diarrhea, frequent bowel movements, and bowel urgency. Patients with UC are at greater risk for hospitalization, surgery, and colorectal cancer. To reduce these risks, the goals of UC treatment are changing from mainly addressing symptoms to reducing inflammation at a deeper histologic, or microscopic, level. The inflammation in UC causes distinct microscopic changes in the colon, which can be assessed after collecting biopsies or tissue samples. This review provides an overview of histologic remission (when no signs of inflammation are seen in tissue samples viewed under a microscope) as a treatment goal in UC.Histologic remission has been shown to be associated with lower rates of relapse, hospitalization, surgical removal of the colon, and colorectal cancer. However, using histologic remission as a treatment target can be difficult due to varying definitions and the many different scoring assessments available to healthcare providers. Updated guidance from regulatory agencies and academic organizations has helped align definitions of histologic remission and how to assess histologic healing in clinical trials.The introduction of targeted advanced therapies has allowed for deeper healing with the potential for histologic resolution. This enables clinicians and researchers to aim for treatment targets that are harder to achieve but have a greater impact for patients in the course of their disease. New technologies such as artificial intelligence, high-resolution endoscopy, and digital pathology have also led to targets beyond histologic healing, aiming to restore the function of the colon's mucosal barrier and disease clearance.

Human-derived bacterial strains mitigate colitis via modulating gut microbiota and repairing intestinal barrier function in mice.

BACKGROUND: Unbalanced gut microbiota is considered as a pivotal etiological factor in colitis. Nevertheless, the precise influence of the endogenous gut microbiota composition on the therapeutic efficacy of probiotics in colitis remains largely unexplored. RESULTS: In this study, we isolated bacteria from fecal samples of a healthy donor and a patient with ulcerative colitis in remission. Subsequently, we identified three bacterial strains that exhibited a notable ability to ameliorate dextran sulfate sodium (DSS)-induced colitis, as evidenced by increased colon length, reduced disease activity index, and improved histological score. Further analysis revealed that each of Pediococcus acidilactici CGMCC NO.17,943, Enterococcus faecium CGMCC NO.17,944 and Escherichia coli CGMCC NO.17,945 significantly attenuated inflammatory responses and restored gut barrier dysfunction in mice. Mechanistically, bacterial 16S rRNA gene sequencing indicated that these three strains partially restored the overall structure of the gut microbiota disrupted by DSS. Specially, they promoted the growth of Faecalibaculum and Lactobacillus murinus, which were positively correlated with gut barrier function, while suppressing Odoribacter, Rikenella, Oscillibacter and Parasutterella, which were related to inflammation. Additionally, these strains modulated the composition of short chain fatty acids (SCFAs) in the cecal content, leading to an increase in acetate and a decrease in butyrate. Furthermore, the expression of metabolites related receptors, such as receptor G Protein-coupled receptor (GPR) 43, were also affected. Notably, the depletion of endogenous gut microbiota using broad-spectrum antibiotics completely abrogated these protective effects. CONCLUSIONS: Our findings suggest that selected human-derived bacterial strains alleviate experimental colitis and intestinal barrier dysfunction through mediating resident gut microbiota and their metabolites in mice. This study provides valuable insights into the potential therapeutic application of probiotics in the treatment of colitis.

Identified S100A9 as a target for diagnosis and treatment of ulcerative colitis by bioinformatics analysis.

Ulcerative colitis (UC) is a chronic, recurrent inflammatory bowel disease. UC confronts with severe challenges including the unclear pathogenesis and lack of specific diagnostic markers, demanding for identifying predictive biomarkers for UC diagnosis and treatment. We perform immune infiltration and weighted gene co-expression network analysis on gene expression profiles of active UC, inactive UC, and normal controls to identify UC related immune cell and hub genes. Neutrophils, M1 macrophages, activated dendritic cells, and activated mast cells are significantly enriched in active UC. MMP-9, CHI3L1, CXCL9, CXCL10, CXCR2 and S100A9 are identified as hub genes in active UC. Specifically, S100A9 is significantly overexpressed in mice with colitis. The receiver operating characteristic curve demonstrates the excellent performance of S100A9 expression in diagnosing active UC. Inhibition of S100A9 expression reduces DSS-induced colonic inflammation. These identified biomarkers associated with activity in UC patients enlighten the new insights of UC diagnosis and treatment.

Fragility index analysis for randomized controlled trials of approved biologicals and small molecule drugs in inflammatory bowel diseases.

INTRODUCTION: Biologics and small molecules have been increasingly applied in Crohn's disease (CD) and ulcerative colitis (UC). But the robustness of their trials has not been evaluated. METHODS: We initially collected all the approved biologics or small molecules for CD or UC up to December 1, 2022. Databases were then queried by keywords in chemical name and CD or UC. Randomized controlled trials (RCTs) in the two-arm, 1:1 design were included. Fragility index (FI) and fragility quotient (FQ) were subsequently calculated. RESULTS: We included twenty-eight RCTs, including nine pivotal trials listed in approval labels, nineteen non-pivotal trials not included in the labels. The median sample size was 99 [IQR, 60-262] and the median number of loss-of-follow-up (LFU) was 14 [IQR, 8-43]. Pivotal trials in the labels had the median FI of 8 [IQR, 4-14, n = 6] that was marginally higher than non-pivotal trials (3 [IQR, 2-4], p = 0.08). The median FQ was 0.0330 [IQR, 0.1220-0.0466] and 0.0310 [IQR, 0.0129-0.0540] for pivotal and non-pivotal trials, respectively (p = 1.0). The sample size and FI were significantly correlated (Spearman correlation coefficient [r] = 0.56, 95 %CI 0.21-0.78, p = 0.003). The number of total events was also significantly correlated with FI (r = 0.53, 95 %CI 0.17-0.77, p = 0.006). Study p-values were significantly associated with FI (p = 0.01): trials with p-values < 0.001 had the highest median FI of 10 [IQR, 6-17]. No factor was found strongly correlated with FQ. CONCLUSION: Results from trials assessing administration-approved biologics or small molecules for treating CD or UC were vulnerable to small changes by measuring FI or FQ. Pivotal studies contributing to regulatory approvals exhibited a relatively higher degree of resilience compared to non-pivotal trials.

Effects of moxibustion on visceral hypersensitivity and colonic inflammatory response in mice with chronic ulcerative colitis. / è‰¾ç¸å¯¹æ ¢æ€§æºƒç–¡æ€§ç»“è‚ ç‚Žå°é¼ å† è„é«˜æ•åŠç»“è‚ ç»„ç»‡ç‚Žæ€§ååº”çš„å½±å“.

OBJECTIVES: To observe the effects of moxibustion at "Zusanli" (ST36) on the expression levels of tumor necrosis factor (TNF)-α, TNF receptor 1 (TNF-R1), p38 mitogen-activated protein kinase (P38 MAPK), and transient receptor potential vanilloid 1 (TRPV1) in the colon tissue of mice with chronic ulcerative colitis (UC), so as to explore the underlying mechanisms of moxibustion in improving visceral hypersensitivity in chronic UC. METHODS: Male C57BL/6J mice were randomly divided into normal group, normal with moxibustion (NM) group, model group, and model with moxibustion (MM) group, with 10 mice in each group. The chronic UC model was established by drinking 2.5% dextran sodium sulfate for 3 cycles. Mice in the NM and MM groups received moxibustion at ST36 for 20 min, 5 days per week with a 2-day break, for a total of 4 weeks. The disease activity index (DAI) score of each group was evaluated before and after treatment. The minimum volume threshold of abdominal wall retraction reflex (AWR) was measured to observe the intestinal sensitivity of mice. The colon length was measured. The pathological changes of colon tissue were observed by HE staining. The expression of mucin in colon goblet cells was detected by periodate Scheff staining. The intestinal fibrosis was observed by Masson staining. The number of trypsin-positive cells (i.e., mast cell) and the expression level of TNF-α in colon tissue were detected by immunofluorescence staining. The expression levels of TNF-R1, P38 MAPK and TRPV1 in colon tissue were detected by immunohistochemistry. RESULTS: Compared with the normal group after treatment, the model group showed increased DAI score (P<0.001), decreased AWR minimum volume threshold (P<0.01), shortened colon length (P<0.001), significant inflammatory infiltration in the colon tissue, reduced mucin secretion (P<0.01), increased collagen fiber deposition (P<0.001), and elevated expression levels of TNF-α, TNF-R1, P38 MAPK, and TRPV1 (P<0.001, P<0.01, P<0.05). Compared with the model group, the MM group showed decreased DAI score (P<0.01), increased AWR minimum volume threshold (P<0.001), elongated colon length (P<0.001), reduced inflammatory cell infiltration, improved integrity of mucosal glandular structure, enhanced mucin secretion (P<0.01), decreased collagen fiber deposition (P<0.001), decreased number of mast cells in the colon tissue (P<0.001), and decreased expression levels of TNF-α, TNF-R1, P38 MAPK, and TRPV1 (P<0.001, P<0.01, P<0.05). There were no significant differences in the above index between the NM group and the normal group. CONCLUSIONS: Moxibustion can reduce visceral hypersensitivity, alleviate inflammatory infiltration and fibrotic damage in the colon tissue of mice with chronic UC. These effects may be associated with the down-regulation of TNF-α, TNF-R1, P38 MAPK, and TRPV1 expression in colon.

Global trends and hotspots of ulcerative colitis based on bibliometric and visual analysis from 1993 to 2022.

Ulcerative colitis (UC) has seen a significant increase over the past 3 decades. However, our understanding of its etiology, pathogenesis, and pharmacological treatment remains limited. This comprehensive review aims to address these gaps by analyzing trends, evaluating previous research, and providing insights for future investigations. We conducted a bibliometric analysis of UC-related papers indexed in the Web of Science from 1993 to 2022. The author, organization, country, and keyword networks in the field of UC were visualized. A total of 36,483 papers were included, showing a continuous upward trend. Most research on UC was conducted in universities, with hospitals leading in high-quality studies. The United States emerged as the primary contributor, followed by China and the United Kingdom. The overall quality of UC-related publications improved, indicating sustained interest in the field. The keywords related to UC was classified into 9 clusters. Keywords detection revealed that UC research focused mainly on the discovery of its etiology and exploration of treatment methods, with research directions evolving from initial treatment of UC and related diseases to clinical trials of UC and subsequently incorporating genomics and bioinformatics techniques to study UC and explore new therapeutic methods and drugs, including recent advances in gut microbiota. Our study identified gaps in understanding the etiology, pathogenesis, and treatment of UC. Future research in UC should focus on genomics, personalized treatment, microbial therapy and leveraging machine learning and artificial intelligence. These areas hold the potential for improving UC diagnosis, treatment, and management.

A prospective, controlled multisite trial of yoga in pediatric inflammatory bowel disease.

AIM: To investigate whether a structured yoga program improves health-related quality of life (HRQOL) and self-efficacy in pediatric patients receiving care for inflammatory bowel disease (IBD). METHODS: IBD patients who were 10-17 years old participated in a 12 week, in-person yoga intervention at two clinical sites. Outcomes were measured at time of consent (T0), start of yoga (T1), and completion of yoga (T2) and 3 months after yoga completion (T3) using the IMPACT-III, Pediatric Quality of Life Inventory (PedsQL), and General Self Efficacy (GSE) scales. RESULTS: Seventy-eight patients were enrolled. Fifty-six patients completed nine or more classes. 73.2% had Crohn's disease and 26.8% ulcerative colitis or IBD-unclassified. A significant increase in IMPACT-III was seen from T1 to T3 (mean change of 5.22, SD = 14.33, p = 0.010), in the PedsQL (mean change = 2.3, SD = 10.24, p = 0.050), and GSE (mean change = 1, SD = 3.60, p = 0.046). 85.2% of patients reported yoga helped them to control stress. Long-term data was available for 47 subjects with 31.9% (n = 15) continuing to practice yoga one to 3 years after study completion. CONCLUSION: This structured 12-week yoga program showed significant improvements in HRQOL and general self-efficacy, particularly 3 months after classes were concluded suggesting that yoga's benefits may persist. Yoga is a safe and effective adjunct to standard medical care to improve QOL and self-efficacy in youth with IBD.

Sterile Fecal Microbiota Transplantation Boosts Anti-Inflammatory T-Cell Response in Ulcerative Colitis Patients.

Ulcerative colitis is a chronic immune-mediated disease of unclear etiology, affecting people of different ages and significantly reducing the quality of life. Modern methods of therapy are mainly represented by anti-inflammatory drugs and are not aimed at a specific pathogenetic factor. In this study, we investigated the effect of transplantation of sterile stool filtrate from healthy donors on the induction of anti-inflammatory immune mechanisms. It was shown that performing such a procedure in patients with ulcerative colitis caused the appearance of T helper cells in the blood, which reacted to the content of sterile stool filtrates in an antigen-specific manner and produced IL-10. At the same time, cells of the same patients before therapy in response to the addition of sterile stool filtrates were less reactive and predominantly produced IL-4, indicating its pro-inflammatory skewing. The obtained data demonstrated the effect of an anti-inflammatory shift in the T-helper response after transplantation of sterile stool filtrate, which increased and persisted for at least three months after the procedure.

Challenges in the diagnosis and treatment of inflammatory bowel disease in Latin America.

The incidence and prevalence of inflammatory bowel disease (IBD), namely Crohn's disease and ulcerative colitis, have increased in Latin America over the past few decades. Although incidence is accelerating in some countries in the region, other areas in Latin America are already transitioning into the next epidemiological stage-ie, compounding prevalence-with a similar epidemiological profile to the western world. Consequently, more attention must be given to the diagnosis and management of IBD in Latin America. In this Review, we provide an overview of epidemiology, potential local environmental risk factors, challenges in the management of IBD, and limitations due to the heterogenity of health-care systems, both public and private, in Latin America. Unresolved issues in the region include inadequate access to diagnostic resources, biological therapies, tight disease monitoring (including treat to target therapy, surveillance and prevention of complications, drug monitoring), and specialised IBD surgery. Local guidelines are an important effort to overcome barriers in IBD management. Advancements in long-term health-care policies will be important to promote early diagnosis, access to new treatments, and improvements in research in Latin America. These improvements will not only affect overall health care but will also lead to optimal prioritisation of IBD-related costs and resources and enhance the quality of life of people with IBD in Latin America.

The INHABIT (synergIstic effect of aNtHocyAnin and proBIoTics in) Inflammatory Bowel Disease trial: a study protocol for a double-blind, randomised, controlled, multi-arm trial.

Ulcerative Colitis (UC), a type of Inflammatory Bowel Disease (IBD), is a chronic, relapsing gastrointestinal condition with increasing global prevalence. The gut microbiome profile of people living with UC differs from healthy controls and this may play a role in the pathogenesis and clinical management of UC. Probiotics have been shown to induce remission in UC; however, their impact on the gut microbiome and inflammation is less clear. Anthocyanins, a flavonoid subclass, have shown anti-inflammatory and microbiota-modulating properties; however, this evidence is largely preclinical. To explore the combined effect and clinical significance of anthocyanins and a multi-strain probiotic, a 3-month randomised controlled trial will be conducted in 100 adults with UC. Participants will be randomly assigned to one of four groups: anthocyanins (blackcurrant powder) + placebo probiotic, probiotic + placebo fruit powder, anthocyanin + probiotic, or double placebo. The primary outcome is a clinically significant change in the health-related quality-of-life measured with the Inflammatory Bowel Disease Questionnaire-32. Secondary outcomes include shotgun metagenomic sequencing of the faecal microbiota, faecal calprotectin, symptom severity, and mood and cognitive tests. This research will identify the role of adjuvant anti-inflammatory dietary treatments in adults with UC and elucidate the relationship between the gut microbiome and inflammatory biomarkers in this disease, to help identify targeted individualised microbial therapies. ANZCTR registration ACTRN12623000630617.

Nanomedicine-mediated drug delivery for potential treatment of inflammatory bowel disease: a narrative review.

Background & aims: Inflammatory bowel disease (IBD) is a condition characterized by chronic inflammation of the gastrointestinal tract, manifesting as either Crohn's disease (CrD) or ulcerative colitis (UC). Current treatment options for CrD and UC primarily focus on symptom management. In recent years, advancements in nanotechnology have increased the clinical applicability of nanoparticles (NPs) in treating IBD. This review explores the current research on NP-mediated drug-delivery systems for IBD treatment and assesses its advantages and limitations. Results: The authors examine diverse nanomedicine applications for IBD and address the current challenges and prospects in the field to advance nanomediated therapies in the future. Conclusion: Innovative NP-based treatment strategies promise a reliable and effective approach to IBD management.

Microbiota and mucosal gene expression of fecal microbiota transplantation or placebo treated patients with chronic pouchitis.

Altered microbiota and impaired host immune function have been linked to the pathogenesis of pouchitis. We used 16S rRNA gene sequencing and RNA sequencing data from a previous randomized clinical trial (RCT) on fecal microbiota transplantation (FMT) therapy in 26 chronic pouchitis patients with one-year follow-up. We analyzed changes in both luminal and mucosal microbiota composition, as well as in host mucosal gene expression to gain insights into the host-microbiota interactions possibly underlying clinical outcomes of the patients. Antibiotic type and pattern of use were significant drivers of the luminal microbiota at baseline. Differential gene expression analysis indicated transition from ileal to colonic gene expression in the pouch, and upregulation in inflammation- and immune system-related pathways in the pouch. At 4 weeks, the non-relapsed FMT patients had a lower microbiota dissimilarity to the donor than the non-relapsed placebo patients (p = .02). While two FMT-treated patients showed a shift toward the donor's microbiota during the one-year follow-up, the overall FMT microbiota modulation effect was low. Patient's luminal and mucosal microbiota profiles were unstable in both FMT and placebo groups. Expression of the chemokine receptor CXCR4 was downregulated at 52 weeks compared to the baseline in the non-relapsed patients in both FMT and placebo groups. Microbiota modulation by FMT seems to be low in this patient group. The microbiota composition or alterations did not explain the relapse status of the patients. Some evidence for remission-related host gene expression pattern was found; specifically, CXCR4 expression may have a role in sustained remission.