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Background: It is important to identify patients with monogenic IBD as management may differ from classical IBD. In this position statement we formulate recommendations for the use of genomics in evaluating potential monogenic causes of IBD across age groups., Methods: The consensus included paediatric IBD specialists from the Paediatric IBD Porto group of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and specialists from several monogenic IBD research consortia. We defined key topics and performed a systematic literature review to cover indications, technologies (targeted panel, exome and genome sequencing), gene panel setup, cost-effectiveness of genetic screening, and requirements for the clinical care setting. We developed recommendations that were voted upon by all authors and Porto group members (32 voting specialists)., Results: We recommend next-generation DNA-sequencing technologies to diagnose monogenic causes of IBD in routine clinical practice embedded in a setting of multidisciplinary patient care. Routine genetic screening is not recommended for all IBD patients. Genetic testing should be considered depending on age of IBD-onset (infantile IBD, very early-onset IBD, paediatric or young adult IBD), and further criteria, such as family history, relevant comorbidities, and extraintestinal manifestations. Genetic testing is also recommended in advance of hematopoietic stem cell transplantation. We developed a diagnostic algorithm that includes a gene panel of 75 monogenic IBD genes. Considerations are provided also for low resource countries., Conclusions: Genomic technologies should be considered an integral part of patient care to investigate patients at risk for monogenic forms of IBD., (Copyright © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Anemia is one of the most common extraintestinal manifestations of inflammatory bowel disease (IBD). It can be asymptomatic or associated with nonspecific symptoms, such as irritability, headaches, fatigue, dizziness, and anorexia. In IBD patients, the etiology of anemia is often multifactorial. Various causes include iron deficiency, anemia of inflammation and chronic disease, vitamin deficiencies, hemolysis, or myelosuppressive effect of drugs. Anemia and iron deficiency in these patients may be underestimated because of their insidious onset, lack of standardized screening practices, and possibly underappreciation that treatment of anemia is also required when treating IBD. Practitioners may hesitate to use oral preparations because of their intolerance whereas intravenous preparations are underutilized because of fear of adverse events, availability, and cost. Several publications in recent years have documented the safety and comparative efficacy of various intravenous preparations. This article reviews management of anemia in children with IBD, including diagnosis, etiopathogenesis, evaluation of a patient, protocol to screen and monitor patients for early detection and response to therapy, treatment including parenteral iron therapy, and newer approaches in management of anemia of chronic disease. This report has been compiled by a group of pediatric gastroenterologists serving on the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) IBD committee, in collaboration with a pediatric hematologist, pharmacist, and a registered dietician who specializes in pediatric IBD (IBD Anemia Working Group), after an extensive review of the current literature. The purpose of this review is to raise awareness of under-diagnosis of anemia in children with IBD and make recommendations for screening, testing, and treatment in this population.

The rate of pediatric inflammatory bowel disease (IBD) has been increasing over the last decade and this increase has occurred most rapidly in the youngest children diagnosed <6 years, known as very early-onset inflammatory bowel disease (VEO-IBD). These children can present with more extensive and severe disease than older children and adults. The contribution of host genetics in this population is underscored by the young age of onset and the distinct, aggressive phenotype. In fact, monogenic defects, often involving primary immunodeficiency genes, have been identified in children with VEO-IBD and have led to targeted and life-saving therapy. This position paper will discuss the phenotype of VEO-IBD and outline the approach and evaluation for these children and what factors should trigger concern for an underlying immunodeficiency. We will then review the immunological assays and genetic studies that can facilitate the identification of the underlying diagnosis in patients with VEO-IBD and how this evaluation may lead to directed therapies. The position paper will also aid the pediatric gastroenterologist in recognizing when a patient should be referred to a center specializing in the care of these patients. These guidelines are intended for pediatricians, allied health professionals caring for children, pediatric gastroenterologists, pediatric pathologists, and immunologists.

The use of murine models to investigate human diseases has been an invaluable tool. In the areas of inflammation and oncogenesis, such models have provided unique insights into pathogenesis and mechanisms to evaluate potential therapy. As such, one facet of these disease processes links inflammation and cancer. Inflammation is associated with at least 15% of the world's malignancies. One example of this relationship is documented in the association between colitis and colorectal cancer. To date, the precise molecular events linking inflammation and cancer remain unclear. A new paradigm that may bridge these processes includes the cancer stem cell hypothesis. In this review, murine models of colitis, colon cancer, and colitis-associated cancer are discussed in reference to the potential of this paradigm to clarify the relationship of these devastating diseases.

Ulcerative colitis has been associated with psychological distress and an aberrant immune response. The immunomodulatory role of systemic cytokines produced during experimental intestinal inflammation in tonic immobility (TI) defensive behavior remains unknown. The present study characterized the TI defensive behavior of guinea pigs subjected to colitis induction at the acute stage and after recovery from intestinal mucosa injury. Moreover, we investigated whether inflammatory mediators (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, IL-10, and prostaglandins) act on the mesencephalic nucleus, periaqueductal gray matter (PAG). Colitis was induced in guinea pigs by intrarectal administration of acetic acid. The TI defensive behavior, histology, cytokine production, and expression of c-FOS, IBA-1, and cyclooxygenase (COX)-2 in PAG were evaluated. Colitis reduced the duration of TI episodes from the first day, persisting throughout the 7-day experimental period. Neuronal c-FOS immunoreactivity was augmented in both columns of the PAG (ventrolateral (vlPAG) and dorsal), but there were no changes in IBA-1 expression. Dexamethasone, infliximab, and parecoxib treatments increased the duration of TI episodes, suggesting a modulatory role of peripheral inflammatory mediators in this behavior. Immunoneutralization of TNF-α, IL-1β, and IL-8 in the vlPAG reversed all effects produced by colitis. In contrast, IL-10 neutralization further reduced the duration of TI episodes. Our results reveal that peripherally produced inflammatory mediators during colitis may modulate neuronal functioning in mesencephalic structures such as vlPAG., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background, Objectives and Design: Arachidonic acid 15-lipoxygenase (ALOX15) has been implicated in the pathogenesis of inflammatory diseases but since pro- and anti-inflammatory roles have been suggested, the precise function of this enzyme is still a matter of discussion. To contribute to this discussion, we created transgenic mice, which express human ALOX15 under the control of the activating protein 2 promoter (aP2-ALOX15 mice) and compared the sensitivity of these gain-of-function animals in two independent mouse inflammation models with Alox15-deficient mice (loss-of-function animals) and wildtype control animals., Materials and Methods: Transgenic aP2-ALOX15 mice were tested in comparison with Alox15 knockout mice (Alox15 -/- ) and corresponding wildtype control animals (C57BL/6J) in the complete Freund's adjuvant induced hind-paw edema model and in the dextran sulfate sodium induced colitis (DSS-colitis) model. In the paw edema model, the degree of paw swelling and the sensitivity of the inflamed hind-paw for mechanic (von Frey test) and thermal (Hargreaves test) stimulation were quantified as clinical readout parameters. In the dextran sodium sulfate induced colitis model the loss of body weight, the colon lengths and the disease activity index were determined., Results: In the hind-paw edema model, systemic inactivation of the endogenous Alox15 gene intensified the inflammatory symptoms, whereas overexpression of human ALOX15 reduced the degree of hind-paw inflammation. These data suggest anti-inflammatory roles for endogenous and transgenic ALOX15 in this particular inflammation model. As mechanistic reason for the protective effect downregulation of the pro-inflammatory ALOX5 pathways was suggested. However, in the dextran sodium sulfate colitis model, in which systemic inactivation of the Alox15 gene protected female mice from DSS-induced colitis, transgenic overexpression of human ALOX15 did hardly impact the intensity of the inflammatory symptoms., Conclusion: The biological role of ALOX15 in the pathogenesis of inflammation is variable and depends on the kind of the animal inflammation model., (© 2023. The Author(s).)

Xylooligosaccharides riched in xylobiose and xylotriose exhibit various biological activities as prebiotics. However, the prebiotics of xylooligosaccharides for regulating the intestinal microbiota in colitis models has been rarely investigated. In this study, differences in prebiotic ability of xylooligosaccharides samples from paper mulberry branches using different methods, including autohydrolysis (termed as 170AH), sequent purification by polystyrene-divinylbenzene copolymer resin (termed as 170AH-XAD), and enzymatic hydrolysis using endo- β -1,4-xylanase (170AH-XAD-E) were investigated. Results revealed that 170AH-XAD-E possessing higher fractions of xylobiose and xylotriose exhibited the best performance in vitro by promoting the proliferation of Bifidobacterium adolescentis and Lactobacillus acidophilus , with utilization rates of 92.30% and 91.00%, respectively. Additionally, 170AH-XAD-E outperformed the other samples in increasing the species' abundance of in vivo intestinal microbiota in colitis mouse model induced by Escherichia coli. Furthermore, 170AH-XAD-E selectively promoted the growth of Bacteroides , while inhibiting the proliferation of Firmicutes , Proteobacteria , and Actinobacteriota. These abilities of 170AH-XAD-E may be due to its potential to upregulate the population of intestinal microbiota associated with the functional abundance of Cell wall/membrane/envelope biogenesis and Inorganic ion transport and metabolism. Overall, this work demonstrates that XOS with high contents of xylobiose and xylotriose possesses excellent potential as intestinal microbiota regulators and anti-colitis agents. [Display omitted] • Xylooligosaccharides riched with xylobiose and xylotriose enhance probiotic growth. • Xylooligosaccharides with higher xylobiose and xylotriose increase gut flora. • Xylooligosaccharides with higher xylobiose and xylotriose alleviate colitis. [ABSTRACT FROM AUTHOR]

Background: The novel peptide neuropeptide W (NPW) was originally shown to function in the control of feeding behavior and energy homeostasis. The aim of this study was to elucidate the putative preventive and therapeutic effects of NPW on colitis-associated oxidative injury and the underlying mechanisms for its action., Methods: Sprague-Dawley rats in the acute colitis groups received NPW (0.5, 1 or 5 µg/kg/day) injections prior to induction of colitis with acetic acid, while the chronic colitis groups were treated after the induction of colitis. In both acute and chronic colitis (CC) groups, treatments were continued for 5 days and the rats were decapitated at the 24th hour of the last injections and colon tissues were collected for assessments., Results: NPW pretreatment given for 5 days before colitis induction, as well as treating rats with NPW during the 5-day course of CC, abolished colonic lipid peroxidation. NPW treatment prevented colitis-induced reduction in blood flow, diminished neutrophil infiltration, and pro-inflammatory cytokine responses. NPW pretreatment only at the higher dose reduced colonic edema and microscopic score and preserved colonic glutathione stores. Elevations in cyclooxygenase (COX) enzyme activity and COX-1 protein level during the acute phase of colitis as well as reduction in COX-2 were all reversed with NPW pretreatment. In contrast, NPW treatment was effective in reducing the elevated COX-2 concentration during the chronic phase., Conclusions: NPW alleviates acetic acid-induced oxidative colonic injury in rats through the upregulation of colonic blood flow as well as the inhibition of COX-2 protein expression and pro-inflammatory cytokine production., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: There is a subset of intestinal failure patients with associated chronic intestinal inflammation resembling inflammatory bowel disease. This study aimed to evaluate factors associated with chronic intestinal inflammation in pediatric intestinal failure., Methods: This was a single-center retrospective case-control study of children <18 years old with intestinal failure. Cases were defined by abnormal amounts of chronic intestinal inflammation on biopsies. Children with diversion colitis, eosinophilic colitis, or isolated anastomotic ulceration were excluded. Cases were matched 1:2 to intestinal failure controls based on sex, etiology of intestinal failure, and duration of intestinal failure. Multivariable conditional logistic regression was used to compare clinical factors between cases and controls, accounting for clustering within matched sets. A subgroup analysis was performed assessing factors associated with escalation of anti-inflammatory therapy., Results: Thirty cases were identified and matched to 60 controls. On univariate analysis, longer parenteral nutrition (PN) duration (1677 vs 834 days, P = 0.03), current PN use (33.3% vs 20.0%, P = 0.037), and culture-proven bacterial overgrowth (53.3% vs 31.7%, P = 0.05) were associated with chronic intestinal inflammation. On multivariable analysis, no variable reached statistical significance. On subgroup analysis, duration of intestinal failure, location of inflammation, and worst degree of inflammation on histology were associated with escalation of therapy., Conclusions: PN dependence and intestinal dysbiosis are associated with chronic intestinal inflammation in children with intestinal failure. Severity of inflammation is associated with escalation of therapy. Further analysis is needed to assess these associations and the efficacy of treatments in this population., Competing Interests: J.D.O. is an independent contractor as “Speaker” for Janssen and consultant for Skygenics. The remaining authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Immune checkpoint inhibitors (ICPIs) have revolutionized cancer therapy, although immune-related adverse events (irAEs) remain a serious issue. The clinical characteristics of colitis induced by ICPIs are very similar to inflammatory bowel disease. Recently, cluster of differentiation 8 positive (CD8 + ) lymphocyte infiltration into organs has been associated with the onset of irAEs. The present study compared the histological infiltration of CD8 +  lymphocytes in irAE colitis with that in other colitis., Methods: Newly diagnosed and untreated patients were retrospectively enrolled. Biopsy specimens were obtained from endoscopic areas of high inflammation for immunohistochemical analysis of the number of cluster of differentiation 4 positive (CD4 + ) and CD8 +  lymphocytes in the high-powered microscopic field with the most inflammation., Results: A total of 102 patients [12 with irAE colitis, 37 with ulcerative colitis (UC), 22 with Crohn's disease (CD), and 31 with ischemic colitis (IC)] were analyzed. In irAE colitis, CD8 +  lymphocyte infiltration was significantly greater than that of CD4 +  lymphocytes (p < 0.01). The amount of CD8 +  lymphocyte infiltration was significantly higher in irAE colitis than in UC (p < 0.05), CD (p < 0.05), and IC (p < 0.01). The CD8 + /CD4 +  ratio was also significantly higher in irAE colitis (p < 0.01 versus UC, CD, and IC, respectively). The optimal cutoff CD8 + /CD4 +  ratio for diagnosing irAE colitis was 1.17 (sensitivity 83%, specificity 84%). The optimal cutoff number of CD8 +  lymphocytes for diagnosing irAE colitis was 102 cells per high-power field (sensitivity 75%, specificity 81%)., Conclusions: Greater CD8 +  lymphocyte infiltration and a higher CD8 + /CD4 +  ratio may be simple and useful biomarkers to distinguish irAE colitis from other forms of colitis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The latest consensus standards for patients with inflammatory bowel disease published by the European Crohn's and Colitis Organisation conclude that optimizing quality of care in inflammatory bowel disease involves information and education after diagnosis. A scoping review was performed to identify educational interventions in newly diagnosed inflammatory bowel disease patients. A systematic literature search was conducted using five databases and gray literature. Inclusion criteria were studies with at least one group of patients whom were less than 2 years from their initial inflammatory bowel disease diagnosis. The review process initially identified 447 articles, resulting in four relevant studies: three randomized controlled trials and one pre-/post-test. Only one study exclusively included newly diagnosed inflammatory bowel disease patients. All studies included a multidisciplinary assessment and three were based on a group intervention, but none of them was described in enough detail to be replicated. The content was the same for all patients regardless of the time elapsed since diagnosis. Education of newly diagnosed patients does not seem to be a priority given the lack of publications meeting our criteria despite the evidence of their need. Interventions and outcomes are heterogeneous. Interventions did not consider patient needs and suggest that they centered more on the professional than on the patient. More evidence is clearly needed about this topic., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Society of Gastroenterology Nurses and Associates.)

Recently we demonstrated that in inflammatory bowel disease (IBD) macrophage-oxidative burst activity is increased and NADPH oxidase mRNA is induced. The herbal phenylethanoid acteoside isolated from Plantago lanceolata L. was shown to exhibit anti-oxidative potential. Using the dextran sulphate sodium (DSS)-induced colitis model, in this study we have assessed whether systemic application of acteoside affects colitis. Colitis was induced by DSS in Balb/c mice. Treatment with acteoside (120, 600 microg/mouse/day) was performed intraperitoneally. The colon lengths were determined. Colonic tissue was scored histologically (max. score 8) by a blinded investigator. T cells isolated from mesenteric lymph nodes (MLN) were stimulated with anti-CD3 antibody in the presence of interleukin (IL)-2 (final concentration 10 U/ml). After incubation for 24 h, IL-1beta, IL-6, IL-12 tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma levels in supernatants were analysed by the beadlyte cytokine detection system. Histological scoring of colonic tissue revealed that application of acteoside was followed by a significantly improved histological score. In acute colitis the histological score was 3.2 with acteoside versus 5.2 with phosphate-buffered saline (PBS) (P < 0.02). In chronic colitis both 120 microg (3.3 versus 5.2) or 600 microg acteoside (3.0 versus 5.2) significantly ameliorated colitis (both P < 0.02). Stimulated MLN from mice with chronic DSS-induced colitis treated with acteoside showed a significant down-regulation of IFN-gamma secretion (195 pg/ml with 600 microg acteoside versus 612 pg/ml with PBS, P < 0.02). Inhibition of oxidative burst activity with acteoside reduced mucosal tissue damage in DSS colitis and could be a therapeutic alternative for IBD treatment. Further studies of this agent are warranted.

Background: Recent progress in ulcerative colitis (UC) treatment has been remarkable, and various medications have been applied. However, some patients with UC are refractory to treatment and convert to surgery., Aim: To investigate the role of colonic mucosal Wnt-5a expression in the pathogenesis of UC and the effect of bioactive Wnt-5a peptide on colitis in mice., Methods: Wnt-5a peptide was intraperitoneally administered to mice every day from the beginning of dextran sulfate sodium (DSS) treatment. The severity of colitis was evaluated based on body weight change, colonic length, and histological scores. Colonic mucosal TNF-α and KC mRNA expression levels were measured. This study included 70 patients with UC in clinical remission. Wnt-5a, TNFα, and IL-8 mRNA expression in the rectal mucosa were measured by quantitative real-time polymerase chain reaction using biopsy materials. Wnt-5a mRNA expression levels were compared between patients who relapsed and those in remission. We examined the correlation of Wnt-5a expression with TNF-α and IL-8 expression., Results: Wnt-5a peptide significantly attenuated the severity of DSS-induced colitis. Moreover, mucosal TNF-α and KC mRNA expression were significantly suppressed by Wnt-5a peptide treatment. Wnt-5a mRNA levels were significantly lower in patients with subsequent relapse than in those who remained in remission. Mucosal Wnt-5a was inversely correlated with TNF α and IL-8 expression., Conclusion: Wnt-5a peptide suppressed colitis in mice, and decreased Wnt-5a expression was strongly associated with relapse in patients with UC. Wnt-5a may have an inhibitory effect on mucosal inflammation in UC, and Wnt-5a peptide could be a new therapeutic strategy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: We previously reported that clumps of a few epithelial cells were scattered in ulcer regions in a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis (UC)., Aims: To determine the ectopically localized epithelial clumps might be derived from stem cells or their daughter progenitor cells., Methods: Female BALB/c mice were administered DSS in drinking water for 6 days, followed by withdrawal of DSS for 6 days. Histological and immunohistochemical examinations were conducted in the distal region and proximal region of the colorectum to determine expression of stem cell markers in the epithelial clumps., Results: Similar to the characteristics of UC, the ulcers were more severe in the distal region close to the anus than in the proximal region of the colorectum. Quantitative analyses revealed that the epithelial clumps appeared in relation to the severity of the ulcer, and they expressed the cell adhesion molecules E-cadherin and β-catenin. Among stem cell markers, the epithelial clumps primarily expressed +5 cell marker Dll1 as reserved intestinal stem cells, followed by +4 cell marker Bmi1 and crypt stem cell marker Lgr5 in that order. Nuclear expression of Sox9, but not nuclear β-catenin, was identified in the clumps., Conclusion: The present results suggest that most epithelial clumps comprised crypt-derived, reserved stem cells, which might have potential for mucosal healing., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The response rate of hepatitis B virus (HBV) vaccination in patients with inflammatory bowel disease (IBD) is variable. Increasing dose or accelerated schedule is the suggested strategy to improve seroconversion., Aim: We performed a meta-analysis to determine the pooled response rate of HBV vaccination and to identify the predictors of seroconversion., Methods: We searched PubMed, Embase and Cochrane library databases. Studies reporting the response of HBV vaccination in IBD patients were included. Response was recorded as adequate immune response (AIR, >10 IU/L) and Effective immune response (EIR, >100 IU/L). Pooled AIR and EIR rates were calculated for different doses (10-20 μg or 40 μg) and schedules (standard: 0, 1 and 6 months or accelerated: 0, 1 and 2 months). Meta-analysis was performed to identify the predictors of response., Results: Twenty-one studies including 2602 patients were eligible. Pooled AIR and EIR rates after HBV vaccination were 62% (95% CI, 55-68) and 42% (95% CI, 37-48), respectively. Pooled AIR and EIR rates for standard and double dose were similar. Pooled AIR and EIR rates were also comparable for different schedules of HBV vaccination. Gender, IBD subtype and disease activity did not affect the response rate. Use of immunosuppression [immunomodulators (RR: 0.73, 95% CI, 0.62-0.87) and anti-TNFs (RR: 0.72, 95% CI, 0.60-0.87)] was a predictor of poor immune response compared to no immunosuppressive therapy., Conclusion: Patients with IBD have a poor serological response after HBV vaccination. HBV screening and vaccination should preferably be done before starting the immunosuppressive drugs., (© 2022 John Wiley & Sons Ltd.)

The importance of inflammatory bowel disease (IBD) dedicated nurses in endoscopy services is poorly explored. Non-IBD healthcare professionals who work in endoscopy units may underestimate the discomfort and the secondary psychological distress that endoscopic procedures cause in IBD patients. We performed a nationwide survey to evaluate the level of knowledge of nurses working in endoscopy facilities throughout Italy related to IBD patients' needs undergoing endoscopic procedures. A non-validate 45 items questionnaire divided into six sections was assembled by a group of experts and supervised by nurses and IBD-physicians as part of the board of IGIBD, ANOTE-ANIGEA and AGGEI. The questionnaire was sent to 397 nurses of which 335 (84.4%) responded to the questionnaire. The median level of knowledge registered was 29 ± 12, corresponding to a medium level of knowledge based on the scores described in the method section. One hundred eighty-three nurses (54.6%) reported a high score, 113 (33.7%) a medium score, and 39 (11.6%) a low score. The majority of nurses worked in high volume endoscopy centers, where the 48% were educated in IBD management. A Low level of knowledge was recorded regarding disease severity definition, bowel preparation strategies in severe colitis and evaluation of perianal fistula. This nationwide survey clearly shows that there is a need for endoscopic nurses to acquire specific knowledge in the IBD field. Dedicated pathways for IBD management in endoscopy, continuous educational programs for nurses and further studies to improve nurse education are needed., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Society of Gastroenterology Nurses and Associates.)

Background: Youth who experience IBD-associated stigma may manifest increased worry about aversive symptoms that can intrude on their participation in routine activities (eg, school, social events), potentially resulting in limited opportunities for reinforcement and increased depressive symptoms. The present study examined an IBD stigma → IBD worry → illness intrusiveness → depressive symptoms serial mediation model, in which stigma was hypothesized to confer an indirect effect on youth depressive symptoms through the serial effects of stigma on IBD worry and illness intrusiveness., Methods: Youth with IBD (N = 90) between the ages of 10 and 18 years were recruited from a pediatric gastroenterology clinic and completed measures of IBD stigma, IBD worry, illness intrusiveness, and depressive symptoms., Results: In addition to several independent direct effects among the modeled variables, results revealed a significant IBD stigma → IBD worry → illness intrusiveness → depressive symptoms serial mediation path (effect = 0.63, 95% CI = 0.22 to 1.20), controlling for youth sex and IBD severity., Conclusions: The experience of IBD-related stigma may prompt increased worry about IBD symptoms, independent of the influence of disease activity. Further, heightened worry appears to amplify youths' experience of IBD-imposed limitations on routine and rewarding activities, increasing their risk for experiencing depressive symptoms. Our findings highlight the importance of regular screening for depressive symptoms, as well as the identification of potential risk factors associated with emotional adjustment difficulties. Stigma-specific treatment modules could be integrated within existing cognitive-behavioral approaches for reducing worry and depressive symptoms in youth with IBD., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Purpose of Review: Very early-onset inflammatory bowel disease (VEO-IBD) is a rare presentation defined as onset of intestinal inflammation at the age of <6 years. Some of these young children develop IBD because of inherent defects in immune or epithelial cell function resulting from deleterious mutations in genes involved in mucosal homeostasis. Here, we provide an overview of the clinical, genetic and immunologic approach in patients with VEO-IBD., Recent Findings: More than 50 different monogenic disorders directly causing IBD have been identified in the last decade; most of them present with unique clinical features in the first years of life. Such a diagnosis may facilitate the administration of targeted therapies and is important for genetic counseling. Nevertheless, a monogenic disorder is identified only in a minority of patients with VEO-IBD. Consequently, different demographic, clinical and histologic features should prompt a detailed genetic and immunologic workup in patients with IBD., Summary: A diagnosis of monogenic IBD can have a huge impact on patient's care, enabling in some cases to provide personalized therapies. Clinicians should be aware of unique features of such disorders, and complete a detailed genetic and immune workup in selected cases, even when disease manifests beyond a young age.

Background: Quality of care in inflammatory bowel disease (IBD) has received much attention internationally; however, the available surveys focus on health professionals rather than patients., Aims: To assess the experiences of healthcare for people living with IBD against established Australian IBD Standards., Methods: An online cross-sectional survey was conducted with Australians ≥16 years old recruited via Crohn's & Colitis Australia membership, public and private clinics and the Royal Flying Doctor Service. Participants completed a questionnaire incorporating items addressing the Australian IBD Standards 2016, the Picker Patient Experience Questionnaire, IBD Control Survey and the Manitoba Index., Results: Complete data were provided by 731 respondents (71.5% female, median age 46 years, ranging from 16 to 84 years). While the majority (74.8%) were satisfied with their IBD healthcare, the care reported did not meet the Australian IBD Standards. Overall, 32.4% had access to IBD nurses, 30.9% to a dietician and 12% to a psychologist in their treating team. Participants managed by public IBD clinics were most likely to have access to an IBD nurse (83.7%), helpline (80.7%) and research trials (37%). One third of respondents reported waiting >14 days to see a specialist when their IBD flared. Participants received enough information, mostly from medical specialists (88.8%) and IBD nurses (79.4%). However, 51% wanted to be more involved in their healthcare., Conclusions: These data show discordance between expectations of patients and national standards with current levels of service provision, which fail to deliver equitable and comprehensive IBD care., (© 2019 Royal Australasian College of Physicians.)

Infantile and very early onset inflammatory bowel disease (VEOIBD) are a rare phenomenon wherein patients develop intestinal inflammation with typical IBD symptoms before ages 2 and 6, respectively. In recent years, there has been an increasing number of monogenetic immunological disorders identified that lead a child to develop VEOIBD. We present a case of an infant boy who presented with hematochezia and thrombocytopenia in the first week of life and developed IBD by the age of 1 month. Additional clues to his diagnosis included lymphopenia and nuclear herniation observed in his neutrophils. Compound heterozygous damaging variants were identified in WD Repeat Domain 1 (WDR1) by whole-exome sequencing (WES) and represents a novel cause of VEOIBD. Our patient's IBD and immunologic phenotype was successfully treated by hematopoietic stem cell transplant (HSCT).

The goal of the current study was to evaluate the anti-inflammatory effect of Arthrocen against acetic acid-induced colitis in rats. Acute inflammation was produced through intrarectal administration of 2 ml diluted acetic acid (4%) solution. All interventions were carried out for 5 days after colitis induction. Arthrocen was administered orally at doses of 30, 60, and 120 mg kg -1  day -1 . Then, macroscopic and microscopic studies were performed. Myeloperoxidase (MPO) activity and tumor necrosis factor-α (TNF-α) activity were measured by biochemical and ELISA methods, respectively. Immunohistochemistry was done to investigate the expression of pNF-κB. The results of this study demonstrated that Arthrocen reduced macroscopic and microscopic damage compared to the acetic acid group. Furthermore, Arthrocen decreased the activity of MPO and TNF-α as well as the protein expression of pNF-kB in rat colon tissue. The results of the current study revealed the anti-inflammatory activity of Arthrocen in acetic acid mediated colon inflammation through suppressing the NF-κB pathway. PRACTICAL APPLICATIONS: Inflammatory bowel disease (IBD) is an immune-mediated chronic relapsing disorder affecting the gastrointestinal tract (GIT) characterized by chronic bowel inflammation. A plant-based dietary supplement containing avocado and soy unsaponifiable extracts in a ratio of 1:2 is known as Arthrocen. Arthrocen can be used as a complementary drug beside current drugs in clinical trials for the treatment of IBD., (© 2020 Wiley Periodicals LLC.)

Purpose of Review: In the context of the rising incidence and complexity of inflammatory bowel disease (IBD), telehealth offers new ways to support remote and efficient delivery of healthcare services. The aim of this review is to assess the current status of telehealth services in the management of IBD and challenges to adopting telehealth in clinical practice., Recent Findings: Different modalities of telehealth such as virtual clinics and remote patient monitoring have been studied in many IBD centers. They are found to be associated with high patient acceptance, decreased healthcare costs, improved quality of life, treatment adherence, and disease knowledge among patients. The major challenges encountered in the integration of telemedicine into clinical practice include risks to patient privacy and confidentiality, requirement for informed consent, lack of uniform reimbursement policies, operational difficulties, provider acceptance, and licensing., Summary: Telehealth is an effective, efficient, and low-cost intervention that can address increasingly complex care of patients with IBD. However, for telemedicine to be adopted widely, new policies and reforms need to reduce the burden of physician licensing in multiple states, allow for receipt of all telehealth services in the patient's home or office, and require reimbursement for services on par with an office visit.

Checkpoint inhibitor-induced side effects such as diarrhea and colitis occur in up to 30% of patients. We present a case of recurrent episodes of checkpoint inhibitor-induced colitis and subsequent Fournier gangrene that resolved after ileostomy formation. Once the Fournier gangrene and colitis had resolved, the ileostomy was reversed. However, within only 4 days, another serious flare-up of colitis occurred, necessitating emergent re-formation of the ileostomy. Expertise in the management of side effects of immune checkpoint inhibitor therapy is currently limited. Although most side effects are mild to moderate and transient, a minority of patients suffer from life-threatening complications, such as colitis. The creation of an ileostomy might be a valid treatment option in severe or recurrent colitis due to immune checkpoint inhibitor therapy. Intestinal diversion surgery may be useful if conservative treatment has failed, similar to other forms of immune-mediated intestinal inflammation.

Introduction and aim. There is no safe and efficient treatment of the chronic intestinal inflammation. Kappa Opioid Receptors (KOP) are found not only in the central nervous system, but also in the gastrointestinal tract. Studies showed that KOP agonist can reduce inflammation in numerous experimental inflammatory models. The aim of the study was to assess if activation of KOP will give anti-inflammatory action in the experimental model of colitis. Material and methods. Dextran Sulfate Sodium was given to mice for 7 days, following 14 days of water, this cycle was repeated twice. We used a selective KOP agonist, U50488, at the dose of 1mg/kg injected intraperitoneally every second day. Following morphological grading, colonic tissues were isolated for molecular analysis. In vitro tests were performed using the RAW 264.7 macrophage cell line, and lipopolysaccharide (LPS) was used to mimic inflammation. The Griess test and MTT assay were used to evaluated how U50488 affects the cytotoxicity and viability of the cells. Results. Anti-inflammatory properties of U50488 were observed by overall improvement in macroscopic scoring, and improvement in microscopic scoring. Moreover, RT-PCR results show changes in NOS2, IL-1B and Il-6 expression, that indicate anti-inflammatory potential of KOP agonist. Results obtained in vitro confirmed that U50488 affected cell survival and decreased NO release, indicating that it has anti-in- flammatory effects. Conclusion. Activation of KOP with U50488 may become novel approach in treatment of chronic colitis. [ABSTRACT FROM AUTHOR]

Introduction and aim. Growth differentiation factor 11 (GDF11) is a novel member of TGF-β superfamily. Its role is confirmed in embryogenesis, rejuvenation, and aging. GDF11 is involved in inflammatory response as it inhibits the release of pro-inflammatory cytokines and NLRP3 inflammasome activation. Moreover, GDF11 has clinicopathological signifi- cance in colorectal cancer and is proposed as a possible prognostic factor. The aim of our study is to assess the activity of GDF11 during development of colitis and colorectal cancer in mice. Material and methods. Male C57BL/6 mice were used in our experiments. Colitis was induced by dextran sodium sulfate (DSS) addition into drinking water. Single injection of azoxymethane (AOM) and repeated cycles of DSS were used to induce colitis-associated colorectal cancer. At different time points mice were sacrificed. Human and mouse colorectal cancer cell lines were used in our project to verify GDF11 expression. MC-38 cells were stimulated with the cytokines for 24 hours. We isolated RNA and protein to perform real-time RT-PCR and Western Blot. Statistical analysis was performed using GraphPad Software. Results. We found that GDF11 expression at mRNA level is increased in the mouse colon during aging. GDF11 expression is elevated during the experimental colitis and during the period of recovery. GDF11 expression is changed at initial stage of colorectal cancer in mice. Its expression also differs among different human cell lines. LPS induced an increase of GDF11 expression. Conclusion. We confirmed that GDF11 is crucial at all stages of development of experimental colitis and colitis-associated colorectal cancer. [ABSTRACT FROM AUTHOR]

The introduction of new therapeutic agents in chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL), including the new kinase inhibitor idelalisib, has changed the therapeutic landscape of these diseases. However, the use of idelalisib is associated with a peculiar profile of side effects, which require an optimization of the current approach to prophylaxis and supportive treatment. Moving from the recognition that the abovementioned issue represents an unmet need in CLL and FL, a multidisciplinary panel of experts was convened to produce a consensus document aiming to provide practical recommendations for the management of the side effects during idelalisib therapy for CLL and FL. The present publication represents a consensus document from a series of meetings held during 2017. The Panel generated clinical key questions using the criterion of clinical relevance through a Delphi process and explored 4 domains, ie, diarrhea/colitis, transaminitis, pneumonitis, and infectious complications. Using the consensus method, the Panel was able to shape recommendations which may assist hematologist to minimize adverse events and guarantee adherence to treatment in patients with CLL and FL candidate to receive idelalisib. [ABSTRACT FROM AUTHOR]

Dysbiosis caused by dietary changes can alter the intestinal bacterial species and is closely associated with inflammatory bowel disease (IBD). Among the possible treatment options, postbiotics, which act to balance the constituent intestinal microflora, have gained substantial attention. Herein, we investigated the anti-inflammatory effects of heat-killed Lactiplantibacillus argentoratensis (hk-LA) BBLB001 isolated from a marine environment using both cell (Caco2/RAW264.7 cell co-culture) and animal (dextran sodium sulfate [DSS]-induced colitis in mice) models. hk-LA BBLB001 markedly reduced IL-8 secretion in Caco-2 cell culture medium after lipopolysaccharide-mediated stimulation of RAW264.7 cells by enhancing the expression of cell adhesion factors.The body weight loss, reduced inflammatory cytokine levels in the serum and colon tissues, colon shortening, and myeloperoxidase activation caused by DSS in mice were alleviated by hk-LA BBLB001. Similar to that in the intestinal cell model, the gene and protein expressions of cell adhesion molecules in the colon tissue were increased upon hk-LA BBLB001 treatment in DSS-induced colitis mice. We observed increased mucin expression and secretory IgA concentration in colon tissues, suggesting that hk-LA BBLB001 intake may benefit pathogen defense and the regulation of intestinal commensal bacteria. Thus, hk-LA BBLB001 may serve as an instrumental postbiotic material in IBD treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Butyrate can strengthen the intestinal epithelial barrier. However, the mechanisms by which butyrate affects intestinal epithelial cells (IECs) pyroptosis in Crohn's disease (CD) remain unclear. In this study, we collected colonic biopsy samples from CD patients and healthy controls to assess pyroptosis levels. Our findings indicated elevated expression of pyroptosis markers in CD patients, alongside distinct morphological evidence of pyroptosis in IECs. We further investigated the effects of tributyrin on pyroptosis and the cGAS-STING pathway in a trinitrobenzene sulfonic acid-induced colitis rat model. Tributyrin significantly mitigated intestinal inflammation, reduced pathological progression, and inhibited pyroptosis and cGAS-STING pathway activation in the colitis rat model. Similarly, in an in vitro model of IECs pyroptosis, sodium butyrate inhibited pyroptosis and cGAS-STING pathway activation in HT-29 cells. Co-treatment with a cGAS-STING pathway activator and butyrate demonstrated that the activator reversed the inhibitory effects of butyrate on pyroptosis and cGAS-STING pathway activation in both the colitis rat model and HT-29 cells. Mechanistically, the cGAS-STING pathway was found to interact with NLRP3. Taken together, butyrate may mitigate intestinal inflammation in CD by suppressing cGAS-STING-NLRP3 axis-mediated IECs pyroptosis. These findings offer new insights into potential therapeutic strategies for managing CD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bioactive components from Porphyra tenera (PT) have been reported to confer various health benefits. The role of PT in inflammatory bowel disease (IBD) has not been fully investigated. This study aimed to explore the anti-inflammatory properties of PT on dextran sodium sulfate (DSS)-treated mice. PT supplementation attenuated the severity of colitis in DSS-treated mice, evidenced by the reduction of disease activity index (DAI), restoration of colonic histological damage and suppression of abnormal inflammatory response. Sequencing analysis indicated that intake of PT alleviated DSS-induced gut microbiota dysbiosis, accompanied by reversing the generation of short-chain fatty acids (SCFAs) and bile acids (BAs). Overall, our findings demonstrated that supplementation of PT attenuated the severity of intestinal inflammation and ameliorated gut microbiota dysbiosis in a murine colitis model, which provided a rationale for further application of edible seaweeds for preventing inflammation-related disorders in humans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Neuropeptide S receptor 1 (NPSR1) has been implicated in the the onset of inflammatory bowel disease (IBD), though its exact mechanism remains unclear. This study investigates the role of NPSR1 in regulating CD4 + T cell effector function in IBD., Methods: Peripheral blood and colonic mucosal biopsies from IBD patients, as well as dextran sodium sulfate (DSS)-induced mouse colitis models, were analyzed to assess the effects of NPSR1 on colitis and CD4 + T cell-mediated immune responses. NPSR1 knockdown was conducted both in vitro and in vivo to elucidate underlying mechanisms. Expression of NPSR1 and CD4 + T cell-related factors was measured using quantitative real-time PCR, immunoblotting, cytometric bead array, immunofluorescence, and immunohistochemistry. CD4 + T cell effector functions were evaluated through flow cytometry, EdU incorporation assay, Annexin V-FITC/PI staining, and transwell assay., Results: NPSR1 expression was elevated in the intestinal tissues from IBD patients. Its downregulation provided protection in DSS-induced mouse colitis models. NPSR1 correlated positively with CD4 + T cell-mediated inflammation, and its knockdown reduced CD4 + T cell-mediated immune responses and inhibited CD4 + T cell differentiation. Additionally, NPSR1 knockdown decreased CD4 + T cell proliferation, increased apoptosis, and enhanced CCL2-induced migration in vitro, while significantly reducing Th1 cell chemotaxis in vivo., Conclusions: This study demonstrates that NPSR1 promotes chronic colitis by regulating CD4 + T cell effector functions in IBD, offering potential new therapeutic strategies for IBD treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Ulcerative colitis (UC) is a complex, refractory inflammatory bowel disease characterized impared intestinal mucosal barrier and imbalanced M1/M2 macrophage polarization mediating its progression. Formononetin (FN), a bioactive isoflavone with established anti-inflammatory and immunomodulatory properties, shows promise in mitigating UC, yet its therapeutic and underlying mechanisms remain unclear. In this study, colitis was induced in mice by administering 2.5% (w/v) dextran sulfate sodium (DSS) solution for 7 days. Oral (25, 50, and 100 mg/kg) FN for 10 days significantly ameliorated colitis symptoms in a dose-dependent manner, by mitigating body weight loss, reducing disease activity index (DAI), colonic weight, and colonic weight index, while enhancing survival rates and colonic length. Histological analysis revealed FN remarkably suppressed inflammatory damage in colonic tissues. Furthermore, FN modulated the expression of pro- and anti-inflammatory cytokines and enhanced antioxidant capacity. Notably, FN treatment significantly enhanced the expression of tight junction (TJ) proteins (claudin-1, ZO-1, occludin) at both protein and mRNA levels in the colon tissues, suggesting improved intestinal barrier function. Crucially, FN inhibited macrophage infiltration in colonic tissues and rebalanced M1/M2 macrophage polarization. While, macrophage depletion largely abrogated FN's protective effects against colitis, indicating a crucial role for macrophages in mediating FN's therapeutic response. Overall, FN effectively alleviated colitis primarily via modulating inflammatory cytokine expression, enhancing antioxidant capacity, upregulating TJs proteins expression, and remodeling M1/M2 macrophage polarization equilibrium. These findings suggest that FN could be the next candidate to unlocking UC's treatment challenge., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The prevalence and severity of gastrointestinal diseases were increased with age. In this study, the intestinal protective effects of Lactococcus lactis HF08 (HF08) and its derived postbiotic (P-HF08) on D-gal-induced aging mice and D-gal/DSS-induced aging colitis mice were investigated. In D-gal-induced aging mice, both HF08 and P-HF08 alleviated aging-related intestinal barrier dysfunction, inflammatory status, and gut microbiota disorder. The effects of probiotic HF08 were superior to those of postbiotic P-HF08, attributed to ability of HF08 to regulate the gut microbiota. However, in D-gal/DSS-induced aging colitis mice, the effects of P-HF08 on colitis surpassed that of HF08. Specifically, both HF08 and P-HF08 could reduce symptoms of age-related colitis, including reduction of lose weight, the DAI score, colonic shortening, and colon tissue damage. The inhibitory effects of P-HF08 on intestinal inflammation surpassed those of HF08, as evidenced by the levels of colon IL-6, IL-1β, and IL-10. Western blot results demonstrated that the anti-inflammatory effects of P-HF08 were attributed to the downregulation of key proteins in the TLR4/NF-κB pathway. And four potential TLR4 inhibitors were identified from HF08 metabolites (eplerenone, genistein, indoleacrylic acid, and turanose) by molecular docking. Nevertheless, HF08 could better regulate gut microbiota and metabolite in aging-related colitis than P-HF08, which was consistent with the results on aging mice. Overall, our finding revealed that when the intestinal barrier was intact (aging), probiotics showed superior regulation of intestinal microbiota, while postbiotics offered greater safety in case of intestinal barrier damage (aging colitis). This study offered a novel perspective into the applications of probiotics and their derivatives in the aging related gastrointestinal diseases adjuvant therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Psoriasis and inflammatory bowel disease (IBD) are chronic immune-mediated diseases that adversely affect patients' quality of life. Interleukin (IL)-27 plays an important role in a variety of infectious diseases, autoimmune disorders, and cancers. However, its therapeutic effects in psoriasis and colitis remain underexplored. In this study, we evaluated the therapeutic potential of recombinant Lactococcus lactis (L. lactis) expressing IL-27 (pIL-27) in imiquimod-induced psoriasis and dextran sodium sulfate-induced colitis mouse models. In the psoriasis mouse model, oral administration of pIL-27 significantly reduced skin scaling, mitigated weight loss, lowered psoriasis area and severity index scores, diminished epidermal hyperplasia and inflammatory cell infiltration, and decreased inflammatory cytokine levels. In the colitis mouse model, oral administration of pIL-27 alleviated weight loss, improved disease activity index scores, prevented colon shortening, ameliorated histopathological changes, and decreased inflammatory cytokine levels. Furthermore, recombinant L. lactis expressing IL-27 could modulate the gut microbiota, increasing the amount of beneficial bacteria and reducing harmful bacteria in the intestine, thereby alleviating the progression of psoriasis and colitis. These results suggest the potential of IL-27 as a therapeutic option for treating psoriasis and IBD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Benzoylmesaconine (BMA), a major alkaloid derived from the traditional Chinese medicine Aconitum carmichaeli Debx, exhibits potent anti-inflammatory properties. However, the precise mechanism underlying its action remains unclear., Purpose: This study aimed to investigate the inhibitory mechanism of BMA on the NLRP3 inflammasome and assess its therapeutic efficacy in NLRP3-related metabolic diseases., Methods: A classic NLRP3 inflammasome-activated bone marrow-derived macrophage (BMDM) model was established to evaluate BMA's effects on NLRP3 upstream and downstream protein expression, as well as pyroptosis. Two distinct animal disease models, MSU-induced gouty arthritis and DSS-induced colitis, were utilized to validate BMA's anti-inflammatory activity in vivo., Results: In vitro findings revealed that BMA can suppress NLRP3 inflammasome activation by inhibiting interleukin-1β (IL-1β) secretion and GSDMD-N protein expression. This mechanism involved blocking intracellular K + efflux and interfering with the formation of NLRP3 inflammasomes. In vivo studies demonstrated that BMA significantly alleviated inflammatory symptoms in MSU-induced acute gout and DSS-induced colitis models., Conclusion: These findings suggest that BMA effectively inhibits the activation of the NLRP3 signaling pathway through dual mechanisms: reducing intracellular K + efflux and disrupting NLRP3 inflammasome assembly. This multifaceted action highlights the therapeutic potential of BMA for NLRP3-related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by abdominal pain, diarrhea, and rectal bleeding. This study aims to explore the protective effects of a phage cocktail (10 8  PFU/mL of Clostridium perfringens phage, 10 8  PFU/mL of Escherichia coli phage, and 10 8  PFU/mL of Salmonella phage) on a mouse colitis model induced by dextran sulfate sodium (DSS) and its potential toxic effects on normal mice. The results demonstrate that the phage cocktail significantly alleviates clinical symptoms in mice, reduces colon shortening, weight loss, and colonic pathological damage. Furthermore, the phage cocktail markedly suppresses the inflammatory response and safeguards intestinal barrier integrity in the colonic tissues of the mouse colitis model. Preliminary investigation of the toxic effects of the phage cocktail in mice indicates that continuous administration for 14 days does not yield statistically significant differences in hematological and blood biochemical parameters, and specific pathological changes are absent in histopathological examination results. The aforementioned findings suggest that the phage cocktail exhibits anti-inflammatory and intestinal barrier protective effects in the mouse colitis model, and it does not exert significant toxic side effects on mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Ulcerative colitis (UC) is a chronic inflammatory disorder with an unsatisfactory cure rate and mucosal healing is a key treatment objective. Christensenellaceae minuta (C. minuta) has emerged as a next-generation of probiotic for maintaining intestinal health. We investigated the therapeutic efficacy of C. minuta in dextran sulfate sodium (DSS)-induced colitis, focusing on mucosal healing and the underlying mechanisms. C. minuta effectively alleviated colitis and promoted the regeneration of intestinal epithelial cells (IECs). Using 16S rRNA sequencing and metabolomics, we found that C. minuta administration increased beneficial bacteria, decreased pathogenic bacteria, and significantly elevated propionic acid levels. Additionally, C. minuta activated the PI3K-AKT pathway by upregulating systemic and local IGF-1 expression. Inhibiting the PI3K-AKT pathway reduced the therapeutic effects of C. minuta and impaired IEC regeneration. Furthermore, C. minuta promoted macrophage differentiation into the M2 phenotype and decreased proinflammatory factors. We propose that C. minuta alleviates colitis by regulating the gut microbiota, modulating macrophage differentiation, and enhancing mucosal healing by activating the PI3K-AKT pathway via IGF-1 secretion induced by short-chain fatty acids. Our findings provide evidence from animal experiments to support future clinical trials and the therapeutic translation of C. minuta., Competing Interests: Declaration of Competing Interest The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background and Purpose: Activation of AMP-activated protein kinase (AMPK) is essential in maintaining the epithelial tight junction (TJ) barrier. Berberine, a phytochemical AMPK agonist, has been widely reported to ameliorate colitis. Berberine or AMPK activation inhibits cytoskeletal contraction induced by myosin light chain kinase (MLCK), thereby ameliorating TJ barrier defects. We previously found that swiprosin-1, an actin-binding protein, affects MLCK expression. Here, we aimed to reveal the role of swiprosin-1 in the regulation of AMPK/MLCK by berberine., Methods: Caco-2 monolayer transfected with AMPKα1 (or swiprosin-1) siRNA was treated with berberine after being stimulated with TNFα/IFNγ to assess the effect on the TJ barrier. Intestinal epithelial conditional knockout mice for AMPKα1 (or swiprosin-1) were treated with berberine after experimental colitis to evaluate the effect on the TJ barrier. TJ integrity was evaluated by immunoblotting and immunofluorescence for ZO-1 and Occludin., Results: The protection of berberine against TJ barrier damage was blocked by AMPK inhibitor or knockout of AMPKα1 in epithelial cells. Swiprosin-1 was distributed in colonic epithelial cells and upregulated in colitis. Knockout of swiprosin-1 in intestinal epithelial cells ameliorated TJ barrier damage and abolished the protective effect of berberine. Impaired assembly of TJ caused by overexpression of swiprosin-1 was alleviated by MLCK inhibitor, and inhibition of the MLCK pathway by berberine also required the presence of swiprosin-1. In addition, berberine downregulated swiprosin-1 expression in an AMPK-dependent manner., Conclusion: Swiprosin-1 may be a key intermediate molecule in the regulation of the AMPK/MLCK pathway by berberine to attenuate colitis-induced TJ barrier damage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Interleukin (IL)-38 belongs to the IL-36 subfamily within the IL-1 family. Patients with inflammatory bowel diseases (IBD) exhibit higher levels of IL-38 in their intestinal tissue compared to healthy controls, suggesting that IL-38 may play a role in the pathogenesis of IBD. However, IL-38's impact on T cell-mediated immune responses in gastrointestinal inflammation has not been investigated. Therefore, the objective of this work was to elucidate the role of IL-38 in modulating T cells in a mouse model of dextran sulfate sodium (DSS)-induced chronic colitis., Methods: Recombinant IL-38 (rIL-38) was administered intraperitoneally (i.p.) to mice with chronic colitis induced by DSS. Clinical symptoms, length of colon, and histologic alterations were assessed. Cytokine production was quantified using ELISA, and helper T (Th) cell subsets were evaluated via flow cytometry., Results: Administration of recombinant IL-38 (rIL-38) alleviated DSS-induced chronic colitis. In addition, animals with chronic colitis treated with rIL-38 exhibited a significant decrease in the spontaneous production of inflammatory cytokines by neutrophils in the lamina propria. Furthermore, rIL-38 treatment increased the absolute numbers and percentages of regulatory T cells (Tregs) but decreased the absolute numbers and percentages of Th1 and Th17 cells. Moreover, rIL-38 treatment also decreased IL-17A-producing γδT cells substantially., Conclusion: This study's results show that IL-38 reduces the effects of chronic colitis caused by DSS by boosting Treg reactions and reducing Th1/Th17 reactions and IL-17A-producing γδT cells in LPL. Therefore, we propose that IL-38 has the potential to be utilized as a biological therapy agent for IBD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)