Ulcerative colitis is an idiopathic and chronic inflammatory bowel disease, characterized by inflammation of the mucosa of the colon and rectum. Clinical manifestations commonly include abdominal pain, diarrhea (with or without hematochezia), and weight loss. The pathogenesis of ulcerative colitis is multifactorial, involving a combination of genetic predispositions and lifestyle factors. High consumption of processed food, sedentary habits, alcohol intake, and stress are among the lifestyle factors implicated in disease onset and progression. Current treatment strategies focus on managing symptoms and inducing remission, however, the chronic nature of the disease, along with the adverse effects of conventional therapies, often compromises patient's quality of life. Therefore, exploring alternative therapies that can prolong remission and reduce symptom burden is important. Experimental evidence suggests that probiotics may extend remission duration in ulcerative colitis. Moreover, probiotics exhibit efficacy in amelioration clinical symptoms by reducing inflammation markers, preserving, and restoring intestinal epithelial. This review explores the advantages of the administration of probiotics in the treatment of ulcerative colitis, elucidating their mechanism of action.

Hidradenitis suppurativa (HS) is associated with inflammatory bowel disease (IBD). Using healthcare databases, an estimated 2.1% of patients with HS have IBD. Prospective screening of patients with HS with IBD sign/symptom-based questions and fecal calprotectin (FC) has not been studied. Our aim was to evaluate the prevalence of IBD in HS and the utility of a sign/symptom-based questionnaire and FC testing.

All patients with HS attending two clinics were invited to participate. Information was collected on demographics, HS severity, and IBD risk factors. Fecal samples were returned by patients for calprotectin testing (≤ 50 μg/g = negative, 50-150 μg/g = borderline, ≥ 150 μg/g = positive).

We recruited 150 patients including 124 women (82.7%) with a median age of 36 years and Hurley stage 2/3 disease (88.6%); 11 patients had established IBD (7.3%). Up to 44.7% of patients reported gastrointestinal symptoms. In 98 patients who returned a fecal sample for calprotectin measurement, 10 had previously diagnosed IBD (10.3%), 81 had a negative FC (82.7%), 13 had a borderline FC (13.3%) and 4 had a positive FC (4.1%). Among 4 patients with a positive result, 2 had known IBD (50%); 2 without established IBD were referred to gastroenterology and 1 had a negative endoscopy reporting an acute diarrheal illness at the time of their FC. The second patient was diagnosed with endoscopic and histologic Crohn's disease.

We report an IBD prevalence of 8%, higher than previous studies. Routine IBD sign/symptom-based assessment is currently recommended. In our study, this would result in a referral rate of 44.7%. Among 88 FC tests in patients without established IBD, 1 patient was diagnosed with incident occult Crohn's disease. At a number needed to screen (NNS) of 88, routine evaluation of all patients with HS with FC may be justified especially prior to the use of interleukin (IL)-17 antagonists.

MicroRNA 146b (miR-146b) mitigates the progression of inflammatory bowel disease (IBD) by reprogramming macrophage polarization through the induction of interleukin-10 (IL-10), thereby eliciting an anti-inflammatory response, but its application is currently hindered by the lack of safe delivery systems that allow sustained miR-146b expression. Inspired by the probiotic Lactococcus lactis, which can produce extracellular vesicles (EVs) that carry a variety of biomolecules, we successfully constructed a genetically modified L. lactis strain that expresses miR-146b (LL-miR-146b) in a nisin-dependent manner and found that its administration eliminated intestinal inflammation in a murine IBD model. Furthermore, LL-miR-146b remodeled the proinflammatory microenvironment, enhanced the integrity of the intestinal barrier, and manipulated the gut microbiota. We then confirmed that the LL-miR-146b-induced reduction in intestinal inflammation was partially dependent on EVs that contained miR-146b, which modulated the activation of classically activated macrophages (M1 macrophages). Importantly, this treatment showed no significant systemic toxicity. In conclusion, we developed a safe and effective vector for IBD treatment by integrating a strategy for calming cytokine storms with biotherapy.

Free Fatty Acid Receptor 2 (FFA2), also known as GPR43, is a receptor activated by short-chain fatty acids (SCFAs) with fewer than six carbons in their aliphatic chains. This receptor is expressed in immune cells, adipose tissue, the gastrointestinal tract, and pancreatic islet cells, where it plays a crucial role in the modulation of inflammation, lipid metabolism, insulin secretion, and appetite regulation. Extensive research has been conducted to elucidate the structural attributes and physiological functions of FFA2. Furthermore, several synthetic agonists have been developed for FFA2 that can preferentially activate certain G-proteins, demonstrating potential pharmacological advantages in both in vivo and in vitro studies. Herein, we review the structure and physiological functions of FFA2 and its synthetic ligands, discussing the structural basis of FFA2's biased signaling and the potential role of biased ligands targeting this receptor in the treatment of metabolic and neurodegenerative diseases.

Patients with inflammatory bowel diseases (IBD) express concerns about their disease's effects on intimacy and sexuality. This study assessed sexual dysfunction in IBD patients and indirect beneficial effects of IBD-specific cognitive behavioral therapy (CBT) on improving sexual functioning over time.

N = 118 patients participated in a multi-center randomized controlled trial (RCT) and were assigned to either an 8-week 'IBD-specific CBT' intervention or waitlist-control group. Standardized self-report measures assessed sexual functioning (the sexuality item of the Inflammatory Bowel Disease Questionnaire, IBDQ), symptoms of depression and anxiety (Hospital Anxiety and Depression Scale: HADS), health-related quality of life (HRQoL; MOS Short-Form Health Survey: SF-36), and IBD symptoms/disease activity (Simple Clinical Colitis Activity Index: P-SCCAI, Harvey Bradshaw Index: P-HBI). Data were analyzed cross-sectionally and longitudinally by means of repeated measures and mediation analyses.

At baseline, nearly half of patients reported sexual problems, including 21.4% with moderate and 15.5% with (very) severe sexual problems, as well as 10.2% reporting sexual abstinence due to IBD. At baseline, sexual functioning was weakly to moderately associated with symptoms of depression or anxiety (r<-0.4) and physical health complaints (r=.3). Longitudinally, 'IBD-specific CBT' had positive effects on sexual functioning which were mediated by improved depressive symptoms (R2=32.9%).

Impairments in sexual functioning are common in IBD patients, which appears in part related to depressive symptoms. Addressing sexual problems in clinical care is crucial, and this study provided preliminary evidence that 'IBD-specific CBT' directed at mental health outcomes, such as depressive complaints, can parallelly help to alleviate sexual dysfunction.

The combined effects of some modifiable lifestyle factors on incident inflammatory bowel disease (IBD) are uncertain.

To evaluate the combined association between healthy lifestyle behaviours and IBD incidence.

This population-based prospective cohort study used data from the UK Biobank. We included 105,715 participants aged 40-70 who had no IBD diagnosis at baseline in the analyses. The five healthy lifestyle behaviours that we studied were never smoking, optimal sleep, high level of vigorous physical activity, high dietary quality, and moderate alcohol intake. The outcome was the overall incidence of IBD and individual incidences of Crohn's disease (CD) and ulcerative colitis (UC). We derived hazard ratios (HR) and 95% confidence intervals (CI) for associations.

The multivariable adjusted HRs (95% CI) associated with having 1, 2 and 3-5 healthy lifestyle behaviours for IBD incidence compared with those with none of these behaviours were 0.75 (0.59-0.97), 0.72 (0.56-0.92), and 0.50 (0.37-0.68), respectively (p for trend < 0.001). We observed similar findings for CD and UC. Only never smoking exhibited significant independent inverse associations with the overall incidence of IBD (HR 0.70, 95% CI 0.58-0.83, p < 0.001) and the incidence of UC (HR 0.58, 95% CI 0.48-0.72, p < 0.001).

Healthy lifestyle behaviours are significantly associated with lower IBD incidence in middle-aged and elderly individuals, suggesting the potential of lifestyle modifications as a primary prevention strategy for IBD.

The anti-inflammatory effect of the ethanol extract of Momordica charantia in two different chemically induced inflammatory bowel disease models, which are frequently used in experimental studies, was investigated. For this purpose, IBD models were created with acetic acid (AA) and 2,4,6 trinitrobenzene sulphonic acid (TNBS) in rats and 300 mg/kg M.charantia extract was given by oral gavage for 10 days. In the animal experiment phase, a total of 42 animals in six groups were arranged so that two different experimental models could be studied simultaneously. Colon tissues were examined at light and electron microscopy levels. In the microscopic examination, areas of inflammation extending to the muscularis externa were observed in the macroscopically severely damaged areas in both IBD model groups, and epithelial damage, mucosal inflammation, and crypt abscess were observed in the macroscopically less damaged areas. Microscopic large intestine damage was significantly reduced in M.charantia administered groups compared to disease models. TNF-α and IL-1β expression, which was determined to be increased in the AA and TNBS groups immunohistochemically, was observed to decrease in the treatment groups. The surface epithelium was evaluated by electron microscopic observations. This study demonstrates the positive effect of M.charantia ethanol extract on colon histopathology in two different IBD models and highlights the importance of considering inflammation-related cell populations in the treatment of this disease.

Chronic inflammation is a pivotal driver in the progression of atherosclerosis, significantly contributing to the burden of cardiovascular disease (CVD). Patients with chronic inflammatory diseases, such as inflammatory bowel diseases (IBDs) (e.g., ulcerative colitis and Crohn's disease), rheumatological disorders, as well as individuals with auto-immune diseases (such as systemic lupus erythematosus), present a higher risk of major adverse cardiac events (MACEs). Despite their elevated CVD risk, these populations remain underrepresented in cardiovascular research, leading to a critical underestimation of their cardiovascular risk (CVR) in clinical practice. Furthermore, even recent CVR scores poorly predict the risk of events in these specific populations. This narrative review examines the physiopathological mechanisms linking chronic inflammation, immunomodulation, atherosclerosis, thrombosis and cardiovascular events. We review data from epidemiological studies and clinical trials to explore the potential cardiovascular benefits of anti-inflammatory and immunomodulatory therapies. Despite existing evidence, significant gaps in knowledge remain. Future research is mandatory, focusing on innovative strategies for risk stratification and optimization, including lipidomics, proteomics, advanced inflammatory markers, microbiota profiling, and cardiovascular imaging. Addressing these unmet needs will enhance understanding of cardiovascular risk in chronic inflammatory diseases, enabling tailored interventions and better outcomes.

Background/Objectives: Patients with inflammatory bowel disease (IBD) are at a higher risk of developing bone disorders. Awareness and understanding of the disease are crucial for prevention and early diagnosis. Currently, there is no research on the risk factors and knowledge of bone fragility in the population with IBD in Taiwan. This study aimed to evaluate the risk factors and self-assessed knowledge levels of bone health among patients with IBD in Taiwan. Methods: This single-center cross-sectional study included 59 adult patients. Clinical data, blood tests, bone mineral density (BMD), T-score, Z-score, and questionnaires covering self-assessed knowledge, fracture risks, and physical activity were assessed. The patients were divided into normal and low BMD groups. Results: Of all participants, eighteen (30.5%) had low BMD: six (10.2%) had BMD below the expected range, ten (16.9%) had osteopenia, and two (3.4%) had osteoporosis. Vitamin D insufficiency and deficiency were observed in 26.3% and 66.6% of the patients, respectively. According to multivariate analysis, age and sex hormone deficiency are strongly associated with low BMD. Educational interventions significantly improved the patients' self-assessed knowledge levels. Conclusions: Age and sex hormone deficiency are significant factors contributing to low BMD in IBD patients. Not only women but also men with IBD who had symptoms of hypogonadism are at high risk for low BMD. Educational interventions improve self-assessment knowledge regarding the relationship between IBD and bone health.

Curcuminoids, found in turmeric (Curcuma longa L.), include curcumin (CUR), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Although CUR and DMC are well-studied, the anti-inflammatory effects of BDMC remain less explored. Recent studies highlight BDMC's stronger NF-κB inhibition compared to CUR and DMC in cell models, along with its ability to target pathways associated with inflammatory bowel disease (IBD) in DSS-induced colitis mice, reflected by lower disease activity scores and reduced inflammation. This study assessed CUR and BDMC in a DSS-induced colitis mouse model. Dietary administration of CUR or BDMC strengthened tight junction (TJ) proteins, reduced inflammatory cytokine secretion, and attenuated intestinal inflammatory protein expression, thereby alleviating DSS-induced IBD in mice. Furthermore, gut microbiota and short-chain fatty acid analyses revealed that CUR and BDMC effectively regulated gut microbial imbalance and promoted the relative abundance of butyrate-producing bacteria. Furthermore, CUR showed low absorption and was primarily excreted in feces, while BDMC had higher absorption levels. In conclusion, while both BDMC and CUR have potential as adjunct therapies for IBD, BDMC at a concentration of 0.1% showed strong anti-inflammatory effects and enhanced TJ proteins, suggesting that BDMC, even at lower concentrations than CUR, holds promising therapeutic potential and prospects.

Despite industrialization and advances in healthcare, the prevalence of inflammatory bowel disease (IBD), which encompasses Crohn's disease (CD) and ulcerative colitis (UC), is increasing in Taiwan. Population-based studies can estimate the incidence or prevalence of IBD; however, there is a lack of information regarding the disease phenotype. Therefore, this study was designed to investigate the epidemiologic trends of IBD in Taiwan to gain a more comprehensive understanding.

Patient data were reviewed from a prospectively registered study by the Taiwan Society of IBD (TSIBD).

We collected data from 2752 patients with IBD, of whom 881 had CD and 1871 had UC. Their average age was 41.99 ± 15.19 years. The CD group had more male patients than the UC group (67.88% vs. 60.72%; p < .001). The rates of appendectomy, bowel resection, and surgery for perianal disease before IBD diagnosis, along with the increased use of steroids, immunomodulators, and biologics, were higher in the CD group. From 2005 to 2023, the ratio of UC to CD cases in Taiwan decreased, the proportions of patients with colonic and penetrating CD also declined, and the proportion of patients with UC exhibiting ulcerative proctitis increased.

In Taiwan, similar to high-income countries, the ratio of UC to CD cases has declined. The reduced of colonic and penetrating CD indicates that diagnostic awareness has improved and colonoscopic examination has become more comprehensive in Taiwan.

Crohn's Disease (CD) is a chronic inflammatory bowel disease affecting the gastrointestinal tract. The search continues for new markers for assessing the activity of CD. Among them, pro-inflammatory and anti-inflammatory cytokines appear promising. We performed the analysis of cytokine concentrations in blood serum using the Bio-Plex Multiplex system (Bio-Rad), and their correlations with radiological parameters were assessed by magnetic resonance enterography (MRE), and fecal calprotectin levels were measured quantitatively by ELISA and clinical evaluation according to the Crohn's Disease Activity Index (CDAI). Our study found that measuring cytokine serum concentrations can be a valuable tool in the diagnosis and treatment of CD. Positive correlations were reported between contrast enhancement on DCE-MRE and the concentrations of PDGF-BB and RANTES. Also, a positive correlation was found between the delayed-phase of DCE and IL-10 concentration, a strong negative correlation between the delayed-phase of DCE and IL-12 concentration, and a strong positive correlation between the delayed-phase of DCE and RANTES concentrations. A strong positive correlation was also observed between the thickness of the intestinal wall on T2-weighted images and RANTES concentration. Therefore, concentrations of PDGF-BB, RANTES, IL-10 and IL-12 are promising markers of CD activity. The study also demonstrated significant correlations between the severity of disease activity assessed by the CDAI and the concentrations of IL-5, IL-8 and IL-9, as well as positive correlations between the levels of fecal calprotectin and the concentrations of IL-1RA and VEGF. Therefore, the levels of IL-5, IL-8, IL-9, VEGF and IL-1RA may be useful markers in the diagnosis and clinical assessment of disease activity.

Inflammatory bowel disease-related complications are associated with a decreased quality of life, requirement for surgery, and increased morbidity. Endoscopic ultrasound (EUS) is accurate at identifying and characterizing perianal fistulae and abscesses and helps guide treatment decisions. EUS also allows us to accurately assess for mucosal and transmural inflammation and thus can help differentiate Crohn's disease from ulcerative colitis (UC). EUS use can help predict dysplasia in UC, and monitoring transmural inflammation can help assess response to treatment. In addition to diagnostic EUS, therapeutic EUS techniques have been used to endoscopically drain abscesses and bypass strictures in Crohn's disease.

The prevalence and incidence of inflammatory bowel disease (IBD) has increased significantly in Latin America. Extraintestinal manifestations (EIMs) have elevated morbidity and are poorly characterized in the region. Our aim was to describe the characteristics of EIMs in patients with IBD at the Hospital Universitario Fundación Santa Fe de Bogotá, utilizing the EIM classification proposed by the European Crohn's and Colitis Organisation (ECCO).

A cross-sectional study was conducted based on an institutional database of patients with IBD and the EIM definition used by the ECCO. Prevalence and prevalence ratios (PRs) of the EIMs were calculated.

The study included 168 patients, 66 of whom were diagnosed with Crohn's disease (CD) and 102 with ulcerative colitis (UC). A total of 30.4% patients had at least one EIM, and the most frequent were oral ulcers (13.7%), arthritis (10.1%), and uveitis/episcleritis (6.5%). There was a greater prevalence of EIMs in CD (31.8% vs 29.40% in UC) and women (32.47% vs 28.57% in men). There was a significant PR between uveitis/episcleritis and arthritis, erythema nodosum and arthritis, and erythema nodosum and other eye diseases.

Our study shows a high prevalence of EIMs, surpassing that of previous Colombian studies, with a predominance of CD. Oral manifestations stand out as the most common. Prevalence studies on EIMs in Colombia are needed to establish multidisciplinary specialized centers, improving the quality of life of patients with IBD.

With 20-40% of patients who have inflammatory bowel disease (IBD) not responding to therapy, resource use and costs can be high. We performed a descriptive analysis of health-care data for IBD management in the National Health Service to explore potential areas for improvement.

In this exploratory study, we analysed real-world data from the Discover dataset for adults with a diagnosis of incident IBD recorded in northwest London, UK, between 31 March, 2016, and 31 March, 2020. We compared mean visit numbers and primary and secondary care costs per patient to examine resource use and costs for active disease versus remission.

We included 7,733 patients (5,872 with ulcerative colitis [UC], 1,427 with Crohn's disease [CD], and 434 with codes for both [termed IBD-undefined in this study]). Remission was recorded in 19,218 (82%) of 23,488 observations for UC, 4,686 (82%) of 5,708 for CD, and 1,122 (65%) for IBD-undefined observations. Health-care resource use was significantly higher with active disease in all settings except primary care for UC. Total health-care costs were greater with active disease than remission for all diagnoses (all p < 0.0001). The main driver of costs was inpatient hospital care among those with active disease; elective inpatient costs were high among patients with UC and IBD-undefined in remission.

Higher health-care resource use and costs were observed with active disease, which underscores the importance of early induction and maintenance of remission in UC and CD. Updated strategies that incorporate treat to target may offer cost benefits by the offsetting of biologic drug costs with a reduction in costly inpatient hospital stays.

This trial was not registered as it used pseudonymised retrospective data.

Inflammatory bowel diseases (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD), are complex chronic inflammatory intestinal conditions with a multifaceted pathology, influenced by immune dysregulation and genetic susceptibility. The challenges in understanding IBD mechanisms and implementing precision medicine include deciphering the contributions of individual immune and non-immune cell populations, pinpointing specific dysregulated genes and pathways, developing predictive models for treatment response, and advancing molecular technologies. Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool to address these challenges, offering comprehensive transcriptome profiles of various cell types at the individual cell level in IBD patients, overcoming limitations of bulk RNA sequencing. Additionally, single-cell proteomics analysis, T-cell receptor repertoire analysis, and epigenetic profiling provide a comprehensive view of IBD pathogenesis and personalized therapy. This review summarizes significant advancements in single-cell sequencing technologies for enhancing our understanding of IBD, covering pathogenesis, diagnosis, treatment, and prognosis. Furthermore, we discuss the challenges that persist in the context of IBD research, including the need for longitudinal studies, integration of multiple single-cell and spatial transcriptomics technologies, and the potential of microbial single-cell RNA-seq to shed light on the role of the gut microbiome in IBD.

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practically unrelated diseases that fulfill these criteria have started to emerge as multimorbidities during the last decades. Here, we provide a comprehensive overview of diseases encompassed by the epithelial barrier theory and discuss evidence and similarities for their epidemiology, genetic susceptibility, epithelial barrier dysfunction, microbial dysbiosis, and tissue inflammation.

To assess the prevalence of urinary incontinence and the clinical and demographic factors associated with patients with Post-COVID-19 Syndrome.

A cross-sectional study was conducted with 59 participants from Porto Alegre/RS. Data were collected via telephone interviews using a structured instrument, the Functional Status Scale, and the International Consultation on Incontinence Questionnaire - Short Form, between September 2021 and October 2022. Numerical data were analyzed for normality using the Shapiro-Wilk test. Student's t-test with Mann-Whitney's post-hoc was applied for comparison of continuous variables. Fisher's exact test was used for correlation of categorical data.

The sample included 32 women (56.4 ± 11.3 years) and 27 men (49.5 ± 10.7 years). Only women reported post-COVID-19 urinary incontinence (28%), as well as emotional alterations (p=0.006). Urinary incontinence was associated with insomnia (p=0.005).

Urinary incontinence was prevalent only in women and was not affected by COVID-19. Women also exhibited greater emotional alterations. Insomnia was the variable associated with the outcome. Thus far, there is incipient evidence regarding the association of the SARS-CoV-2 infection with the prevalence of urinary incontinence in individuals with Post-COVID-19 Syndrome.

Inflammatory bowel diseases (IBD) are idiopathic disorders characterized by chronic gastrointestinal inflammation. Given conventional therapies' adverse effects and clinical failures, novel approaches are being investigated. Recent studies have highlighted the role of specialized pro-resolving lipid mediators (SPMs) in the active resolution of chronic inflammation. In this regard, omega-3 fatty acid-derived Resolvin D2 (RvD2) appears to play a protective role in the pathophysiology of IBD. Therefore, we characterized the RvD2 pathway and its receptor expression in the intestinal mucosa of experimental colitis induced by dextran sulfate sodium. We also evaluated the preventive impact of an omega-3-enriched diet and the therapeutic efficacy of RvD2 compared with anti-TNF-α treatment. We found an increase in TNFα and IL22 expression and decreased levels of enzymes involved in RvD2 biosynthesis, such as PLA2, 15-LOX, 5-LOX, and its receptor GPR18 in experimental colitis. Omega-3 supplementation reduced the Disease Activity Index (DAI), weight loss, colonic shortening, and inflammation. These results and the increased IL-10 transcriptional levels after RvD2 treatment suggest that this mediator attenuated experimental colitis. These results enhance our understanding of the molecular mechanisms involved in the exacerbated inflammatory response present in experimental colitis and suggest that RvD2 and its omega-3 precursor offer a promising therapeutic approach for IBD.

As a chronic inflammatory bowel disease, the pathogenesis of ulcerative colitis (UC) has not been fully elucidated. N6-methyladenosine (m6A) modification, observed in various RNAs, is implicated in inflammatory bowel diseases. Methyltransferase-like 14 (METTL14) is the major subunit of the methyltransferase complex catalyzing m6A modifications. Here, we designated to examine the regulatory effects and mechanisms of METTL14 on long non-coding RNA (lncRNA) during UC progression. METTL14 knockdown decreased cell viability, promoted apoptosis, increased cleaved PARP and cleaved Caspase-3 levels, while reducing Bcl-2 levels. METTL14 knockdown also led to a significant increase in NF-κB pathway activation and inflammatory cytokine production in the Caco-2 cells treated with TNF-α. Moreover, the suppression of METTL14 aggravated colonic damage and inflammation in our dextran sulfate sodium (DSS)-induced murine colitis model. METTL14 silencing suppressed DHRS4-AS1 expression by reducing the m6A modification of DHRS4-AS1 transcripts. Furthermore, DHRS4-AS1 mitigated inflammatory injury by targeting the miR-206/adenosine A3 receptor (A3AR) axis. DHRS4-AS1 overexpression counteracted the enhancing impact of METTL14 knockdown on TNF-α-induced inflammatory injury in Caco-2 cells. In conclusion, our findings suggest that METTL14 protects against colonic inflammatory injury in UC via regulating the DHRS4-AS1/miR-206/A3AR axis, thus representing a potential therapeutic target for UC.

Inflammatory bowel disease (IBD) is a refractory inflammatory disorder of the intestine, which is probably triggered by dysfunction of the intestinal epithelial barrier. Secretory leukocyte protease inhibitor (SLPI) secreted by colon epithelial cells protects against intestinal inflammation by exerting anti-protease and anti-microbial activities. Daikenchuto (DKT) is one of the most commonly prescribed Japanese traditional herbal medicines for various digestive diseases. Although several animal studies have revealed that DKT exerts anti-inflammatory effects, its detailed molecular mechanism is unclear. This study aimed to clarify the anti-inflammatory mechanism of DKT using a murine colitis model, and to evaluate its potential as a therapeutic agent for IBD.

Experimental colitis was induced in wild-type (WT) mice and SLPI-deficient (KO) mice by dextran sulfate sodium (DSS) after oral administration of DKT. The resultant clinical symptoms, histological changes, and pro-inflammatory cytokine levels in the colon were assessed. Expression of SLPI in the colon was detected by Western blotting and immunohistochemistry. Composition of the gut microbiota was analyzed by 16S rRNA metagenome sequencing and intestinal metabolites were measured by gas chromatography-mass spectrometry analysis. Intestinal epithelial barrier function was assessed by oral administration of FITC-dextran and immunostaining of tight junction proteins (TJPs).

Oral administration of DKT increased the number of butyrate-producing bacteria, such as Parabacteroides, Allobaculum, and Akkermansia, enhanced the levels of short-chain fatty acids, including butyrate, in the colon, induced SLPI expression, and ameliorated DSS-induced colitis in WT mice. We found that mouse colon carcinoma cell line treatment with either DKT or butyrate significantly enhanced the expression of SLPI. Moreover, supplementation of DKT protected the intestinal epithelial barrier with augmented expression of TJPs in WT mice, but not in KO mice. Finally, the composition of the gut microbiota was changed by DKT in WT mice, but not in KO mice, suggesting that DKT alters the colonic bacterial community in an SLPI-dependent manner.

These results indicate that DKT exerts anti-inflammatory effects on the intestinal epithelial barrier by SLPI induction, due, at least in part, to increased butyrate-producing bacteria and enhanced butyrate levels in the colon. These results provide insight into the mechanism of the therapeutic effects of DKT on IBD.

Respiratory viral infections have been implicated in the exacerbation of immune-mediated inflammatory diseases such as inflammatory bowel disease (IBD). To understand the impact of early SARS-CoV-2 variants on the risk of adverse IBD outcomes, we aimed to perform a meta-analysis of high-quality studies.

Cohort studies investigating adverse IBD outcomes (IBD flares, change in disease activity, change in medication, IBD-related hospitalization, and surgery) following COVID-19 were retrieved from MEDLINE and Embase. The Risk Of Bias In Nonrandomized Studies-of Exposure tool was used to assess risk of bias. Random effects model meta-analysis was used to calculate the hazard ratio (HR) for risk of adverse outcomes. Subgroup analysis was performed to estimate risk of outcomes for ulcerative colitis and Crohn's disease patients. Metaregression was performed for sex and duration of follow-up.

Of the 3119 identified studies, 5 were included in the meta-analysis. A total of 34,977 IBD patients with COVID-19 and 53,270 IBD patients without recorded COVID-19 infection were identified. Two of the studies showed a high risk of bias. The random effects model did not show a statistically significant increase in the risk of adverse IBD outcomes following COVID infection (HR:1.05 [0.75-1.46]). There was no significant difference in adverse outcomes between Crohn's disease (HR: 0.91 [0.82-1.02]) and ulcerative colitis patients (HR: 0.83 [0.76-0.90]). Neither the proportion of male participants nor the mean duration of follow-up were found to be significant predictors of effect size.

In this systematic review and meta-analysis, we find that COVID-19 did not increase the risk of adverse IBD outcomes.

Inflammatory Bowel Disease-Associated Arthritis (IBD-associated arthritis) poses a significant challenge, intertwining the complexities of both inflammatory bowel disease (IBD) and arthritis, significantly compromising patient quality of life. While existing medications offer relief, these drugs often initiate adverse effects, necessitating the requirement for safer therapeutic alternatives. Artemisia herba-alba, a traditional medicinal plant known for its anti-inflammatory properties, emerges as a potential candidate. Our computational study focused on examining 20 bioactive compounds derived from A. herba-alba for potential treatment of IBD-associated arthritis. These compounds detected in A. herba-alba include camphor, alpha-thujone, eucalyptol, cis-chrysanthenyl acetate, vicenin-2, 4,5-di-O-caffeoylquinic acid, chlorogenic acid, hispidulin, isoschaftoside, isovitexin, patuletin-3-glucoside, vanillic acid, rutin, schaftoside, lopinavir, nelfinavir, quercetin, artemisinin, gallic acid, and cinnamic acid. Following rigorous analysis encompassing pharmacokinetics, toxicity profiles, and therapeutic targets, compounds with favorable, beneficial characteristics were identified. In addition, comparative analysis with disease-gene associations demonstrated the interconnectedness of inflammatory pathways across diseases. Molecular docking studies provided mechanistic insights indicating this natural plant components potential to modulate critical inflammatory pathways. Overall, our findings indicate that A. herba-alba-derived compounds may be considered as therapeutic agents for IBD-associated arthritis, warranting further experimental validation and clinical exploration.

Cryptosporidiosis is a leading cause of moderate-to-severe diarrhoea globally, and, while it is often self-limited, in immunocompromised individuals, the infection can be associated with significant morbidity and mortality. Diagnosis might be missed or delayed in patients with inflammatory bowel disease (IBD) due to similar presentation, and these patients may also be on immunosuppressive therapies, increasing their risk of infection. Additionally, gastrointestinal infection and dysbiosis may be a risk factor for IBD. Diagnosis, presentation and treatment of cryptosporidiosis in individuals with IBD, as well as any epidemiologic correlations between the two diseases, will be investigated.

MEDLINE, Embase, Cochrane Library, CINAHL, Dissertations and Theses Global and grey literature will be searched. Joanna Briggs Institute (JBI) methodology for scoping reviews was used for the protocol and will be for the review. Two reviewers will independently screen studies and extract data. The evidence and presentation of the results will be analysed with input from the review team. Studies of cryptosporidiosis in patients with IBD will be included. Paediatric, adolescent and adult studies in all patient environments will be included. Cases in which Crohn's disease does not affect the intestine and cases in which cryptosporidial infection is not in the intestine will be excluded.

Published clinical literature will be systematically reviewed, and this work does not directly involve patients. Consequently, ethical review by an institutional review board is not required. Data will be presented at academic conferences, and a culminating report will be published in a peer-reviewed journal. OPEN SCIENCE FRAMEWORK REGISTRATION: https://osf.io/j47mb.

Real-world studies about the effectiveness and safety of vedolizumab (VDZ) in the treatment of inflammatory bowel disease (IBD) in Latin America are scarce. Our study describes the effectiveness and safety of VDZ in Colombian patients with IBD.

EXVEDOCOL (EXperience of VEDOlizumab in COLombia) was a retrospective, multicenter, observational study. Adults with IBD receiving a first dose of VDZ between July 2016 and October 2018 were included. The co-primary outcomes clinical response, and remission, were determined at week 14 and last visit during the maintenance phase (LVMP). The secondary outcomes, deep remission and loss of response were recorded at LVMP.

Thirty-one patients (25 ulcerative colitis (UC), 6 Crohn's disease (CD)) were included. At week 14, clinical response was achieved by 87.1% (27/31) of the patients treated with VDZ, while loss of response was reported in 6.7% (2/30). The remission rate at week 14 was 65.5% (19/29) and 75.9% (22/29) at LVMP. Prior anti-TNF exposure was reported in 61.3% (19 patients) of whom 84.2% (16/19) achieved clinical response at week 14 and 89.5% (17/19) at LVMP. For anti-TNF naïve patients, clinical response was recorded in 91.7% (11/12) at week 14 and 100% (12/12) at LVMP.

High clinical remission rates and safety profile highlight VDZ as a valuable treatment option for IBD patients. Anti-TNF naïve patients may derive greater benefit from therapy. Studies with larger cohorts could confirm these findings.

To investigate the effect and potential mechanism of human-derived urine stem cells (hUSCs) in inhibiting retinal aging by using experimental and bioinformatics. Retinal pigment epithelial cells cultured in vitro, which were randomly divided into normal group, aging group and supernatant of hUSCs group. Cell counting kit-8 detection, senescence-related β-galactosidase, and Annexin V/PI staining were performed to detect cell viability, senescence, and apoptosis. Subsequently, bioinformatics methods were used to explore the underlying mechanisms, in which, targets both hUSCs and aging retina-related targets were obtained from GeneCards. Then, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and protein-protein interaction network were analysis, and the expressional level of hub gene was validated by q-PCR. Supernatant addition of hUSCs promoted markedly cellular proliferation, improved viability and inhibited senescence and apoptosis in vitro. A total of 1476 hUSCs-related targets (Relevance score > 20), 692 retinal disease-related targets, and 732 targets related to disease of aging were selected from GeneCards database, and 289 common targets of hUSCs against aging retina were confirmed through Venn analysis. Enrichment analysis demonstrated that hUSCs might exert its anti-apoptosis efficacy in multiple biological processes, including oxidative stress, inflammation and apoptosis, and core targets were associated with HIF-1, MAPK and PI3K-Akt signal. hUSCs inhibited retinal senescence by regulating multiply targets and signaling pathways, of these, HIF-1, MAPK, and PI3K may be important candidates.

Ferroptosis is a novel type of regulated cell death (RCD) involving iron accumulation and lipid peroxidation. Since its discovery in 2012, various studies have shown that ferroptosis is associated with the pathogenesis of various diseases. Ferroptotic cell death has also been linked to intestinal dysfunction but can act as either a positive or negative regulator of intestinal disease, depending on the cell type and disease context. The continued investigation of mechanisms underlying ferroptosis provides a wealth of potential for developing novel treatments. Considering the growing prevalence of intestinal diseases, particularly colorectal cancer (CRC) and inflammatory bowel disease (IBD), this review article focuses on potential therapeutics targeting the ferroptotic pathway in relation to CRC and IBD.

Sphingosine 1-phosphate receptor modulators (S1PRMs) are an effective treatment for ulcerative colitis (UC). This review summarizes all available randomized trial data on the efficacy and safety of S1PRM therapy.

Multiple publication databases were systematically searched for randomized control trials (RCTs) of adults with moderate to severe UC treated with S1PRMs. Random effects meta-analysis was performed. The risk of bias was assessed using the Cochrane Risk-of-Bias 2 tool, and the overall quality of evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.

We identified 7 RCTs (1737 patients) involving the use of S1PRMs for moderate to severe UC. During induction, S1PRM therapy was efficacious when compared with placebo for clinical remission [RR: 2.65 (95% CI: 2.00, 3.53)], clinical response [RR: 1.68 (95% CI: 1.48, 1.91)], endoscopic improvement [RR: 2.17 (95% CI: 1.76, 2.68)], endoscopic normalization [RR: 2.56 (95% CI: 1.58, 3.83)], mucosal healing [RR: 2.88 (95% CI: 1.94, 4.26)], and histologic remission [RR: 2.42 (95% CI: 1.60, 3.66)]. Similar results were seen throughout the maintenance peroid, although fewer data were available to pool; notably, both sustained [RR: 3.57 (95% CI: 1.23, 10.35)] and steroid-free [RR: 2.92 (95% CI: 1.35, 6.33)] remission were significantly increased by S1PRM. There were no significant differences in adverse events [RR: 1.02 (95% CI: 0.90, 1.15)] and infections [RR: 1.15 (95% CI: 0.82, 1.60)] between S1PRM and placebo.

Pooling of RCT data confirms that S1PRM therapy is both effective and safe for patients with moderate to severe UC.

Nowadays, the pharmacological management of visceral hypersensitivity associated with colitis is ineffective. In this context, targeting purinergic P2X4 receptor (P2X4R), which can modulate visceral pain transmission, could represent a promising therapeutic strategy. Herein, we tested the pain-relieving effect of two novel and selective P2X4R antagonists (NC-2600 and NP-1815-PX) in a murine model of DNBS-induced colitis and investigated the mechanisms underlying their effect. Tested drugs and dexamethasone (DEX) were administered orally, two days after colitis induction. Treatment with tested drugs and DEX improved tissue inflammatory parameters (body weight, spleen weight, macroscopic damage, TNF and IL-1β levels) in DNBS-rats. In addition, NC-2600 and NP-1815-PX attenuated visceral pain better than DEX and prevented the reduction of occludin expression. In in vitro studies, treatment of CaCo2 cells with supernatant from THP-1 cells, previously treated with LPS plus ATP, reduced the expression of tight junctions protein. By contrast, CaCo2 cells treated with supernatant from THP-1 cells, previously incubated with tested drugs, counteracted the reduction of tight junctions due to the inhibition of P2X4R/NLRP3/IL-1β axis. In conclusion, these results suggest that the direct and selective inhibition of P2X4R represents a viable approach for the management of visceral pain associated with colitis via NLRP3/IL-1β axis inhibition.

A multidisciplinary approach to Inflammatory Bowel Disease (IBD) has recently demonstrated a positive impact in pediatric patients, reducing dropout rates and facilitating the transition to adult care. Our study aims to evaluate how this approach influences disease activity, dropout rates, and transition.

We conducted a longitudinal observational study including all patients diagnosed with IBD during pediatric-adolescent age, with a minimum follow-up period of 12 months. For each patient, endpoints included therapeutic approach, need for surgery and transition features.

We included 19 patients: 13 with Ulcerative Colitis (UC) and 6 with Crohn's disease (CD). Most patients required multiple lines of therapy, with over 50% in both groups receiving biological drugs. Compliance was good, with a single dropout in each group (10, 5%). The need for surgery was significantly higher in the CD group compared to the UC group (16% vs. 7.7%, p < 0.01). Mean age at transition was significantly higher in the UC group compared to the CD group (19.2 ± 0.7 years SD vs. 18.3 ± 0.6 years SD, p < 0.05).

In our experience, the multidisciplinary approach to IBD in transition-age patients appears effective in achieving clinical remission, offering the potential to reduce therapeutic dropouts.

The oil derived from Psidium guajava seeds (TKSO) exhibits an abundance of diverse unsaturated fatty acids, notably oleic, linoleic, and α-linolenic acids, conferring substantial health advantages in addressing metabolic irregularities and human diseases. This research endeavor focused on elucidating the impacts of TKSO on colonic inflammatory responses and intestinal microbiota alterations in a murine model of colitis induced by dextran sulfate sodium (DSS), demonstrated that substantial supplementation with TKSO reduces the severity of colitis induced by DSS. Furthermore, TKSO effectively attenuated the abundance and expression of proinflammatory mediators while augmenting the expression of tight junction proteins in DSS-challenged mice. Beyond this, TKSO intervention modulated the intestinal microbial composition in DSS-induced colitis mice, specifically by enhancing the relative presence of Lactobacillus, Norank_f_Muribaculaceae, and Lachnospiraceae_NK4A136_group, while concurrently diminishing the abundance of Turicibacter. Additionally, an analysis of short-chain fatty acids (SCFAs) revealed noteworthy elevations in acetic, propionic, isobutyric, and butyric acids, and total SCFAs levels in TKSO-treated mice. In summary, these findings underscore the potential of TKSO to reduce the severity of colitis induced by DSS in mice through intricate modulation of the intestinal microbiota, metabolite profiles, and intestinal barrier repair, thereby presenting a promising avenue for the development of therapeutic strategies against intestinal inflammatory conditions.

Mesenchymal stem/stromal cells (MSCs) are distributed in various tissues and are used in clinical applications as a source of transplanted cells because of their easy harvestability. Although MSCs express numerous cell-surface antigens, single-cell analyses have revealed a highly heterogeneous cell population depending on the original tissue and donor conditions, including age and interindividual differences. This heterogeneity leads to differences in their functions, such as multipotency and immunomodulatory effects, making it challenging to effectively treat targeted diseases. The therapeutic efficacy of MSCs is controversial and depends on the implantation site. Thus, there is no established recipe for the transplantation of MSCs (including the type of disease, type of origin, method of cell culture, form of transplanted cells, and site of delivery). Our recent preclinical study identified appropriate MSCs and their suitable transplantation routes in a mouse model of inflammatory bowel disease (IBD). Three-dimensional (3D) cultures of MSCs have been demonstrated to enhance their properties and sustain engraftment at the lesion site. In this note, we explore the methods of MSC transplantation for treating IBDs, especially Crohn's disease, from clinical trials published over the past decade. Given the functional changes in MSCs in 3D culture, we also investigate the clinical trials using 3D constructs of MSCs and explore suitable diseases that might benefit from this approach. Furthermore, we discuss the advantages of the prospective isolation of MSCs in terms of interindividual variability. This note highlights the need to define the method of MSC transplantation, including interindividual variability, the culture period, and the transplantation route.

Helminths serve as principal regulators in modulating host immune responses, and their excretory-secretory proteins are recognized as potential therapeutic agents for inflammatory bowel disease. Nevertheless, our comprehension of the mechanisms underlying immunoregulation remains restricted. This investigation delves into the immunomodulatory role of a secretory protein serpin (Emu-serpin), within the larval stage of Echinococcus multilocularis. Our observations indicate that Emu-serpin effectively alleviates dextran sulfate sodium-induced colitis, yielding a substantial reduction in immunopathology and an augmentation of anti-inflammatory cytokines. Furthermore, this suppressive regulatory effect is concomitant with the reduction of gut microbiota dysbiosis linked to colitis, as evidenced by a marked impediment to the expansion of the pathobiont taxa Enterobacteriaceae. In vivo experiments demonstrate that Emu-serpin facilitates the expansion of M2 phenotype macrophages while concurrently diminishing M1 phenotype macrophages, alongside an elevation in anti-inflammatory cytokine levels. Subsequent in vitro investigations involving RAW264.7 and bone marrow macrophages reveal that Emu-serpin induces a conversion of M2 macrophage populations from a pro-inflammatory to an anti-inflammatory phenotype through direct inhibition. Adoptive transfer experiments reveal the peritoneal macrophages induced by Emu-serpin alleviate colitis and gut microbiota dysbiosis. In summary, these findings propose that Emu-serpin holds the potential to regulate macrophage polarization and maintain gut microbiota homeostasis in colitis, establishing it as a promising candidate for developing helminth therapy for preventing inflammatory diseases.