The development of probiotics and prebiotics therapy to ulcerative colitis: a therapy that has gained considerable momentum.

Ulcerative colitis (UC) is increasingly common, and it is gradually become a kind of global epidemic. UC is a type of inflammatory bowel disease (IBD), and it is a lifetime recurrent disease. UC as a common disease has become a financial burden for many people and has the potential to develop into cancer if not prevented or treated. There are multiple factors such as genetic factors, host immune system disorders, and environmental factors to cause UC. A growing body of research have suggested that intestinal microbiota as an environmental factor play an important role in the occurrence and development of UC. Meanwhile, evidence to date suggests that manipulating the gut microbiome may represent effective treatment for the prevention or management of UC. In addition, the main clinical drugs to treat UC are amino salicylate and corticosteroid. These clinical drugs always have some side effects and low success rate when treating patients with UC. Therefore, there is an urgent need for safe and efficient methods to treat UC. Based on this, probiotics and prebiotics may be a valuable treatment for UC. In order to promote the wide clinical application of probiotics and prebiotics in the treatment of UC. This review aims to summarize the recent literature as an aid to better understanding how the probiotics and prebiotics contributes to UC while evaluating and prospecting the therapeutic effect of the probiotics and prebiotics in the treatment of UC based on previous publications.

Targeted delivery of the probiotic Saccharomyces boulardii to the extracellular matrix enhances gut residence time and recovery in murine colitis.

Probiotic and engineered microbe-based therapeutics are an emerging class of pharmaceutical agents. They represent a promising strategy for treating various chronic and inflammatory conditions by interacting with the host immune system and/or delivering therapeutic molecules. Here, we engineered a targeted probiotic yeast platform wherein Saccharomyces boulardii is designed to bind to abundant extracellular matrix proteins found within inflammatory lesions of the gastrointestinal tract through tunable antibody surface display. This approach enabled an additional 24-48 h of probiotic gut residence time compared to controls and 100-fold increased probiotic concentrations within the colon in preclinical models of ulcerative colitis in female mice. As a result, pharmacodynamic parameters including colon length, colonic cytokine expression profiles, and histological inflammation scores were robustly improved and restored back to healthy levels. Overall, these studies highlight the potential for targeted microbial therapeutics as a potential oral dosage form for the treatment of inflammatory bowel diseases.

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.

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.

Biological treatment approach to inflammatory bowel disease is similar in academic and nonacademic centres - prime time for decentralisation of inflammatory bowel disease care?

BACKGROUND: With the increasing number of inflammatory bowel disease (IBD) patients, it is difficult to manage them within specialised IBD teams in academic medical centres: many are therefore treated in nonacademic IBD centres. It is unclear whether the time to introducing biologics is the same in both settings. AIM: We aimed to compare treatment approach with biologics in academic vs. nonacademic centres. METHODS: We analysed Slovenian national IBD registry data (UR-CARE Registry, supported by the European Crohn's and Colitis Organisation), which included 2 academic (2319 patients) and 4 nonacademic IBD (429 patients) centres. RESULTS: The disease phenotype was similar in both settings. In total, 1687 patients received 2782 treatment episodes with biologics. We observed no differences in treatment episodes with TNF-alpha inhibitors (60% vs. 61%), vedolizumab (24% vs. 23%), or ustekinumab (17% vs. 16%) in academic compared to nonacademic centres ( P  = 0.949). However, TNF inhibitors were less often the first biologic in academic centres (TNF inhibitors: 67.5% vs. 74.0%, vedolizumab: 20.3% vs. 17.9%, ustekinumab: 12.1% vs. 8.1%; P = 0.0096). Consequently, more patients received ustekinumab (29.8% vs. 18.3%) and vedolizumab (17.4% vs. 13.5%) and fewer TNF inhibitors (52.7% vs. 68.2%) for Crohn's disease in academic compared to nonacademic centres, with no such differences for ulcerative colitis. The time to initiation of the first biologic from diagnosis was short and similar in both settings (11.3 vs. 10.4 months, P  = 0.2). CONCLUSION: In this nationwide registry analysis, we observed that biological treatment choice was similar in academic and nonacademic settings. These findings support the decentralisation of IBD care.

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.

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.

Medical management of pediatric inflammatory bowel disease.

Management of inflammatory bowel disease, both Crohn's disease (CD) and ulcerative colitis (UC), has seen a seismic shift over the past decade. Over the past five years, there has been the introduction of many new therapies with differing mechanisms of action and a goal of achieving mucosal healing, as well as clinical and biochemical remission (1,2). In addition, management is aimed at restoring normal growth and normalizing quality of life. The ultimate goal is to individualize medical management and determine the right drug for the right patient by identifying which inflammatory pathway is predominant and avoiding unwarranted lack of efficacy or side effects through biomarkers and risk prognostication. Patient's age, location of disease, behavior (inflammatory vs. penetrating/structuring), severity and growth delay all play into deciding on the best treatment approach. Ultimately, early intervention is key in preventing complications. The therapeutic approaches to management can be broken down to nutritional therapy, biologic agents, immunomodulators (including corticosteroids), aminosalicylates and antibiotics. There are numerous other therapies, such as small molecule agents recently approved in adults, which are garnering a great deal of interest.

Surgery for ulcerative colitis.

Ulcerative colitis (UC) has a more severe presentation and rapid progression in pediatric patients, resulting in a greater need for surgical intervention compared to adults. Though medical management of UC has advanced with new biologic therapies, surgery continues to play an important role when disease progresses in the form of worsened or persistent symptoms, hemodynamic instability, or sepsis. The goals of surgical management are to restore intestinal continuity with a functional pouch when possible. While the literature has been growing regarding studies of pediatric patients with UC, high level of evidence studies are limited and most recommendations are based on adult studies. Similar to adults, pediatric patients who have ileal pouches created require surveillance for recurrent disease and cancer surveillance. Unique issues for pediatric patients include monitoring of growth and appropriate transition to adult care after adolescence. This review includes indications for surgical management, overview of staged surgical approaches, and the technical details of the three-stage approach.

Disease clearance in ulcerative colitis: A new therapeutic target for the future.

Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and progression. This has fueled the identification of molecular targets, resulting in a rapidly expanding therapeutic armamentarium. Subsequently, management strategies have evolved from symptomatic resolution to well-defined objective endpoints, including clinical remission, endoscopic remission and mucosal healing. While the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications, studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic measures. Current recommendations lack consideration of histological healing. The simultaneous achievement of clinical, endoscopic, and histologic remission has not been fully investigated. This has laid the groundwork for a novel therapeutic outcome termed disease clearance (DC). This article summarizes the concept of DC and its current evidence.

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.

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.

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.

Savings in social expenditures for work incapacity in patients with inflammatory bowel disease depend on access to innovative therapies in Poland.

OBJECTIVES: Inflammatory bowel diseases (IBD) are an increasing burden for societies. We examined Polish Social Insurance Institution (ZUS) work incapacity expenditures for people with IBD compared with the general population. METHODS: Aggregate data were obtained on ZUS expenditures between 2012 and 2021 in Polish zlotys (PLN). Annual work incapacity benefit expenditures were analyzed and IBD benefit expenditures were examined relative to innovative IBD drug utilization in individual provinces. RESULTS: Between 2012 and 2021, annual ZUS expenditures per person increased, while expenditures per IBD patient decreased. Proportionally, absenteeism was the largest ZUS expenditure in the general population, while disability pensions were the largest in the IBD population. ZUS expenditures due to absenteeism in the general population increased by PLN 282 per person; those due to disability pensions decreased by PLN 85. Disability pension spending due to Crohn's disease (CD) and ulcerative colitis (UC) decreased by PLN 371 and PLN 284, respectively, while absenteeism spending per person with CD and UC decreased (PLN 58 and PLN 35, respectively). Nationwide in 2021, 8.5% of people with CD and 1.9% of those with UC received innovative drugs. The percentage of people receiving innovative drugs and ZUS expenditure per person were inversely related in 9/16 provinces for CD and 5/16 for UC. CONCLUSION: Polish state spending on work incapacity benefits increased in the general population but decreased in people with IBD between 2012 and 2021. Use of innovative drugs was associated with reduced spending per person with IBD in some provinces.

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.