Inflammatory Bowel Disease Patients Research Articles

Gut microbiota metabolite indole-3-acetic acid maintains intestinal epithelial homeostasis through mucin sulfation

ABSTRACT The global incidence and prevalence of inflammatory bowel disease (IBD) are gradually increasing. A high-fat diet (HFD) is known to disrupt intestinal homeostasis and aggravate IBD, yet the underlying mechanisms remain largely undefined. Here, a positive correlation between dietary fat intake and disease severity in both IBD patients and murine colitis models is observed. A HFD induces a significant decrease in indole-3-acetic acid (IAA) and leads to intestinal barrier damage. Furthermore, IAA supplementation enhances intestinal mucin sulfation and effectively alleviates colitis. Mechanistically, IAA upregulates key molecules involved in mucin sulfation, including 3’-phosphoadenosine 5’-phosphosulfate synthase 2 (Papss2) and solute carrier family 35 member B3 (Slc35b3), the synthesis enzyme and the transferase of 3’-phosphoadenosine-5’-phosphosulfate (PAPS), via the aryl hydrocarbon receptor (AHR). More importantly, AHR can directly bind to the transcription start site of Papss2. Oral administration of Lactobacillus reuteri, which can produce IAA, contributes to protecting against colitis and promoting mucin sulfation, while the modified L. reuteri strain lacking the iaaM gene (Lactobacillus ΔiaaM ) and the ability to produce IAA fail to exhibit such effects. Overall, IAA enhances intestinal mucin sulfation through the AHR-Papss2-Slc35b3 pathway, contributing to the protection of intestinal homfeostasis.

The impact of cognitive functions, psychological disorders, and coping strategies on quality of life and disease outcomes in patients with inflammatory bowel diseases: A cross-sectional study.

Quality of life (QoL) in patients with inflammatory bowel disease (IBD) is influenced by several factors, many of which may also impact cognitive function. However, the extent of the interaction among these factors, QoL, and disease outcomes in IBD patients remains unknown. We thus aim to characterize the relationships among psychological disorders, coping mechanisms, cognitive function, and the overall impact on QoL and disease outcomes in patients with IBD. This cross-sectional observational study was conducted at an academic care center. QoL was evaluated using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and disease severity was evaluated using the Harvey-Bradshaw Index (HBI) for Crohn's disease (CD) and the Simple Clinical Colitis Activity Index (SCCAI) for ulcerative colitis (UC). We also used the Hospital Anxiety and Depression scale (HADS). Regression models were used to test the associations among QoL, number of hospitalizations, disease severity, cognitive functioning (working memory [WM] and reaction time), and coping strategies while controlling for anxiety and depressive symptoms, age, and sex. This study included 41 patients (24 patients with CD and 17 with UC) whose mean age was 28.2 (±8.4) years (23 males) and mean SIBDQ score was 51.5 (±10.0). Patients with more WM errors had lower QoL scores (P = .041), whereas patients with higher anxiety levels had lower QoL and more active UC (P = .008 and P = .016, respectively). The use of avoidant coping mechanisms was associated with a significantly higher number of hospitalizations (P = .038), and patients who adopted more emotion-focused coping strategies had a longer illness duration (P = .021). Finally, patients with higher education levels were found to use more active coping mechanisms than others. These results confirm the impact of cognitive, psychological, and coping factors on QoL and disease outcomes in patients with IBD; however, the mechanisms by which these factors interrelate remain unclear. Therapies aimed at improving both cognitive functions and psychological conditions may thus be effective at improving QoL and disease outcomes in IBD patients, and education may play a positive role in promoting the adoption of more effective coping strategies among IBD patients.

Non-canonical NF-κB signaling limits the tolerogenic β-catenin-Raldh2 axis in gut dendritic cells to exacerbate intestinal pathologies

Dendritic cell (DC) dysfunction is known to exacerbate intestinal pathologies, but the mechanisms compromising DC-mediated immune regulation in this context remain unclear. Here, we show that intestinal dendritic cells from a mouse model of experimental colitis exhibit significant levels of noncanonical NF-κB signaling, which activates the RelB:p52 heterodimer. Genetic inactivation of this pathway in DCs alleviates intestinal pathologies in mice suffering from colitis. Deficiency of RelB:p52 diminishes transcription of Axin1, a critical component of the β-catenin destruction complex, reinforcing β-catenin-dependent expression of Raldh2, which imparts tolerogenic DC attributes by promoting retinoic acid synthesis. DC-specific impairment of noncanonical NF-κB signaling leads to increased colonic numbers of Tregs and IgA+ B cells, which promote luminal IgA production and foster eubiosis. Experimentally introduced β-catenin haploinsufficiency in DCs with deficient noncanonical NF-κB signaling moderates Raldh2 activity, reinstating colitogenic sensitivity in mice. Finally, inflammatory bowel-disease patients also display a deleterious noncanonical NF-κB signaling signature in intestinal DCs. In sum, we establish how noncanonical NF-κB signaling in dendritic cells can subvert retinoic acid synthesis to fuel intestinal inflammation.

Resveratrol: A Potential Active Compound for Inflammatory Bowel Disease

Inflammatory Bowel Disease (IBD) is a chronic intestinal disorder consisting of Crohn’s Disease (CD) and Ulcerative Colitis (UC). The highest prevalence of IBD is found in Asia and the cases often occur in the 15-35 group of age. Conventional therapy options that are commonly used have some side effects that impact IBD patients. Therefore, it is necessary to look for new strategies in order to treat IBD regarding their effectiveness, affordability and achieving minimum side effects. Resveratrol, a natural non-flavonoid polyphenolic compound, is commonly found in grapes and various types of berries. It is known to potentially overcome inflammation in IBD through various mechanisms including acting as anti-inflammatory, antioxidant, immunomodulatory effects, and its ability to influence the gut microbiota. This study is aiming for explaining and reviewing further mainly on resveratrol’s extraction method and its mechanism of actions to improve IBD. The resources for this study are done by searching through PubMed, ProQuest, ScienceDirect, MDPI, and Google Scholar with keywords (Inflammatory Bowel Disease) AND (Resveratrol), ⁠(Incidence and Prevalence) of Inflammatory Bowel Disease across Asia, (Threat) AND (Therapy) AND (Inflammatory Bowel Disease), (Bioactive) AND (Therapy) AND (Inflammatory Bowel Disease), (Extraction) AND (Method) AND (Resveratrol), and (Pathophysiology) AND (Inflammatory Bowel Disease). Based on evidence found on resveratrol’s benefits, this compound is apparently promising to alternatively treat IBD, but still needs more research to support its effectiveness.

Exhausted Lag-3+ CD4+ T cells are increased in pediatric Inflammatory Bowel Disease.

T cells are one of the main drivers of inflammatory bowel diseases (IBD). Infliximab (IFX) is used in the treatment of IBD as an anti-inflammatory drug to induce remission by neutralizing TNFα. We determined the individual chemokine/homing receptor and cytokine profile in pediatric IBD patients before and during IFX therapy to identify predictive biomarkers for therapy success. Peripheral blood CD4+ cells from pediatric patients with IBD were immunomagnetically isolated and either directly analyzed by FACS for cell distribution and chemokine/homing receptor expression or evaluated for cytokine production after in-vitro-stimulation. 21 responders (RS) and 21 non-responders (NRS) were recruited. Before IFX therapy, flow cytometry revealed decreased percentages of naïve conventional T cells in pediatric IBD patients. The proportions of CD62-L+ T cells were decreased in both CD and UC therapy responders. The cytokine profile of T cells was highly altered in IBD patients compared to healthy controls (HC). During IFX therapy, the frequencies of conventional memory and regulatory memory T cells expanded in both cohorts. IFX response was marked by a decrease of α4β7+ and IFNγ+ memory T cells in both CD and UC. In contrast, frequencies of Lag-3+ T cells proved to be significantly increased in NRS. These observations were irrespective of the underlying disease. T cells of pediatric IBD patients display an activated and rather Th1/Th17 shifted phenotype The increased expression of the checkpoint molecule Lag-3 on T cells of NRS resembles a more exhausted phenotype than in RS and HC which appeared to be a relevant predictive marker for therapy failure.

Preventable predictive factors of post-colonoscopy colorectal cancer in inflammatory bowel disease.

Post-colonoscopy colorectal cancer (PCCRC) is a colorectal cancer (CRC) diagnosed after a colonoscopy in which no cancer is detected (index colonoscopy). Although the overall cumulative rates of PCCRC are low in both the general population and inflammatory bowel disease (IBD) patients, the overall incidence of PCCRC in IBD is greater than that documented in the general population. This study aimed to identify the index colonoscopy-related factors and patients' characteristics influencing IBD-associated PCCRC development. We carried out an observational, retrospective study in which IBD-associated PCCRCs were diagnosed between 2010 and 2023. The PCCRC group was compared to a control cohort of IBD patients without CRC matched 1:1 by several demographic and clinical features as well as characteristics of index colonoscopy to minimize selection bias. Among 61 CRCs identified, 37 (61%) were PCCRC. Twelve of 37 (32%) PCCRC were diagnosed within 12 months after the previous negative colonoscopy, 15 (41%) within 12-36 months, and 10 (27%) within 36-60 months. In the multivariate analysis, the inadequate bowel preparation of the index colonoscopy (OR: 5.9; 95% CI: 11.1- 31.4) and the presence of high-risk factors for CRC (OR: 24.03; 95% CI: 3.1-187.8) were independently associated with PCCRC. Conversely, prior exposure to immunosuppressors/biologics (OR: 0.17; 95% CI: 0.03-0.83) and random biopsies sampling at index colonoscopy (OR:0.19; 95% CI: 0.04-0.85) were inversely associated with PCCRC. More than 50% of CRCs in our population were PCCRC. PCCRCs were associated with previous inadequate cleansing and occurred more frequently in high-risk patients.

Study of the relationship between genetic variants of IL-18 and the occurrence of inflammatory bowel disease

BackgroundA member of the Interleukin-1 superfamily of cytokines, interleukin-18 (IL-18) is essential to the etiology and progression of inflammatory bowel disease (IBD), a chronic inflammatory illness that affects the digestive system. This study investigated the possible association between two genetic variations, IL-18 rs187238 and IL-18 rs1946518, and IBD in Iraqi patients.MethodsWe evaluated the association of two SNPs of the IL-18 gene at rs187238 and rs1946518 in 54 IBD patients with 19 Crohn’s disease (CD), 35 ulcerative colitis (UC), and 46 healthy controls using PCR-RFLP and PCR-AS techniques for detecting IL-18 rs187238 and IL-18 rs1946518, respectively, by extracting genomic DNA from blood samples.ResultsOur findings indicated no statistically significant variations between the IL-18 rs187238 genotypes and incidences of CD and UC (P = 0.189 and 0.59, respectively). However, the allele frequency showed a significant difference with CD (P = 0.049) but did not show a significant association with UC (P = 0.887). There was no significant association between the genotype and allele frequency of IL-18 rs1946518C/A and CD risk (P = 0.171 and 0.053, respectively). However, there was a significant association between the genotype and allele frequency of IL-18 rs1946518C/A and the risk of developing UC (P = 0.028 and 0.002, respectively).ConclusionThe study revealed statistically significant distinctions between the genetic and allelic frequencies of IL-18 rs1946518 and the probability of developing UC. Nonetheless, there were no significant distinctions between them and CD. According to the research, there were no major differences between IL-18 rs187238 and the two diseases. The frequency of the C allele is connected to CD.

The causal association between inflammatory bowel disease and breast cancer: a bidirectional two-sample Mendelian randomization study.

Objective: This Mendelian Randomization (MR) study aims to explore the potential bidirectional causal relationship between Inflammatory Bowel Disease (IBD) and Breast Cancer (BC). Materials and Methods: We utilized genetic instruments from the summary statistics of genome-wide association studies (GWAS) on IBD among individuals of European ancestry (12,882 cases and 21,770 controls) to investigate the association with breast cancer (14,910 cases and 17,588 controls) and vice versa. The primary causal estimates were obtained using the Inverse Variance Weighting Method (IVW), and the robustness of the results was evaluated through a series of sensitivity analyses. Results: The study found a positive impact of genetically predicted IBD on breast cancer (OR = 1.047; 95% CI:1.009-1.087; p = 0.014); in the analysis of IBD subtypes, genetically predicted Crohn's Disease (CD) also had a positive effect on breast cancer (OR = 1.044; 95% CI:1.015-1.073; p = 0.002), but genetically predicted Ulcerative Colitis (UC) did not show a significant effect on breast cancer (p > 0.05). The reverse Mendelian Randomization analysis indicated that genetically predicted breast cancer promoted the overall occurrence of IBD (OR = 1.112; 95% CI:1.022-1.211; p = 0.014); however, genetically predicted breast cancer did not show a significant correlation with IBD subtypes (CD and UC) (p > 0.05). Genetic predictions indicate a positive effect of Crohn's Disease (CD) on the risk of Estrogen Receptor-Positive Breast Cancer (ER + BC), with (OR = 1.021; 95% CI:1.002-1.040; p = 0.002). Furthermore, a reverse Mendelian randomization analysis reveals that genetically predicted ER + BC contributes to the increased incidence of ulcerative colitis (UC), as indicated by (OR = 1.098; 95% CI:1.032-1.168; p = 0.003). In contrast, genetically predicted Estrogen Receptor-Negative Breast Cancer (ER-BC) has been shown to promote the overall occurrence of inflammatory bowel disease (IBD), with (OR = 1.153; 95% CI:1.008-1.319; p = 0.037). However, bidirectional two-sample Mendelian randomization analyses between other pairs did not reveal any significant associations (p > 0.05). Conclusion: This study elucidates the bidirectional causal association between breast cancer and inflammatory bowel disease, highlighting the necessity of screening for IBD in breast cancer patients and for breast cancer in IBD patients in clinical settings.

A Bottom-Up Liquid Chromatography-Tandem Mass Spectrometry Method for Therapeutic Drug Monitoring of Infliximab: Method Development, Comparison With 2 Enzyme-Linked Immunosorbent Assay Methods, and Evaluation of Anti-Drug Antibody Interference.

Therapeutic drug monitoring is recommended to optimize infliximab use and improve outcome in chronic inflammatory disorders. To describe a simple and affordable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to measure infliximab in serum. Infliximab was measured using winged stable isotope-labeled peptides as internal standards. Linearity, lower limit of measuring interval, limit of detection, precision, accuracy, carryover, and ion suppression were evaluated. Method comparison against 2 enzyme-linked immunosorbent assay (ELISA) methods (Remsima Monitor and IDKmonitor Infliximab) and anti-drug antibody (ADA) interference were evaluated using clinical specimens from inflammatory bowel disease patients (N = 237). Analytical run time and sample preparation time were 5 minutes per sample and 3 hours per batch, respectively. Analytical measurement interval and limit of detection were 0.50 to 50.0 μg/mL (R2 = 0.998) and 0.25 μg/mL, respectively. The intraday and interday imprecision percentage coefficients of variation were less than 6.1%. Accuracy was 94.2% to 98.7%. No significant ion suppression or carryover was observed. Infliximab concentrations measured by LC-MS/MS showed good agreement with those measured by Remsima Monitor (mean percentage difference, 5.7%; 95% CI, -1.2% to 12.6%) but were markedly lower than those measured by IDKmonitor (-32.6%; -35.8% to -29.4%), demonstrating significant bias between ELISAs. Although a good agreement between LC-MS/MS and ELISA was observed for ADA-negative samples (-3.5%; -12.8% to 5.9%), a significant bias was observed for ADA-positive samples (13.6%; 1.7% to 25.6%). This simple, fast, and affordable LC-MS/MS method for infliximab quantitation could improve standardization of infliximab quantitation and optimization of infliximab use in patients with high-titer ADA.

Risk of avascular necrosis in patients with inflammatory bowel disease: Insights from a nationwide cohort study and the impact of corticosteroid use

Background and aimCorticosteroid use is a risk factor for avascular necrosis (AVN) and inflammatory bowel disease (IBD) patients are often exposed to higher corticosteroid usage. We investigated the epidemiology and risk factors of AVN in a nationwide population-based cohort of IBD patients. MethodsPatients newly diagnosed with IBD were identified, and sex- and age-matched participants from the general population were selected in a 1:3 IBD:non-IBD ratio. We investigated newly diagnosed AVN and assessed the incidence rates and risk of AVN with multivariate Cox regression models. ResultsDuring the median follow-up period of 7.22±3.85 years, 357 (0.62 %) were newly diagnosed with AVN. The risk of AVN was higher in IBD (aHR = 1.42, 95 % CI: 1.25–1.62). Ulcerative colitis (UC) patients showed a particularly elevated risk of developing AVN. IBD patients with higher cumulative corticosteroid intake and exposed to a mean prednisolone-equivalent daily dose>20 mg for >1 month were at higher risk of AVN. In Crohn's disease (CD), longer exposure time to >20 mg prednisolone-equivalent presented a trend in increased risk. ConclusionAVN risk was higher in IBD than in those without, particularly in UC and corticosteroid use in IBD could pose a crucial role. These underscore the importance of considering the AVN etiological factors, particularly corticosteroid use.

Novel Insights into the Interaction between Enteropathogenic Bacteria, Pyroptosis and IBD.

Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease of the intestinal tract. The complex pathophysiological mechanisms of IBD include genetic susceptibility, environmental factors, and abnormal immune response of the gut microbiota. Gut microbiota forms a metabolic organ that contributes to human health by performing various physiological functions. The development of IBD is closely linked to the imbalance of gut microbiota. In IBD patients, this imbalance is mainly characterized by an increased abundance of pro-inflammatory microorganisms, specifically enteropathogenic bacteria. Pyroptosis is a form of programmed cell death that can be initiated by microbial infection or host factors. It occurs mostly after intracellular infection with bacteria or pathogens. Other than cell death, its primary effect is to release inflammatory mediators that trigger an inflammatory response in the host. Pyroptosis is an important component of innate immunity and can protect against intracellular risk factors via the inflammatory response. However, excessive activation can cause disease. Previous studies of IBD have indicated a complex relationship between gut microbiota and pyroptosis. Some enteropathogenic bacteria can activate the host's immune system to clear infected cells. This inhibits the proliferation of enteropathogenic bacteria by inducing pyroptosis and restoring the balance of gut microbiota. However, the initial inflammatory response and damage to the integrity of the intestinal barrier are crucial factors that elicit the onset of IBD and favor its progression. This review summarizes research on the role of several common enteropathogenic bacteria in the development of IBD through their induction of host cell pyroptosis. A better understanding of the complex interactions between gut microbiota and pyroptosis should lead to the identification of new targets and treatment options for IBD.

3D printed rectal swabs for assessing the gut microbiome, metabolome and inflammation

Investigating the gut microbiome and metabolome frequently requires faecal samples, which can be difficult to obtain. Previous studies have shown that rectal swabs are comparable to faecal samples for analysing gut microbiota composition and key metabolites. In this study, 3D printed rectal swabs were compared with conventional flocked swabs and faecal samples, due to the potential advantages 3D printing as a technique offers for swab production and development. 16S rRNA gene sequencing, qPCR and metabolite profiling (using 1H-NMR spectroscopy) were performed on swab and faecal samples from healthy participants. Faecal calprotectin and total protein analysis were performed on samples from inflammatory bowel disease (IBD) patients. There were no significant differences between both swab types and faecal samples when assessing key measures of alpha and beta diversity, and differences in the abundance of major phyla. There was a strong correlation between both swab types and faecal samples for all combined metabolites detected by NMR. In IBD patients, there was no significant difference in faecal calprotectin and total protein levels between both swab types and faecal samples. These data lead us to conclude that 3D printed swabs are equivalent to flocked swabs for the analysis of the gut microbiome, metabolome and inflammation.

Gut virome-wide association analysis identifies cross-population viral signatures for inflammatory bowel disease

BackgroundThe gut virome has been implicated in inflammatory bowel disease (IBD), yet a full understanding of the gut virome in IBD patients, especially across diverse geographic populations, is lacking.ResultsIn this study, we conducted a comprehensive gut virome-wide association study in a Chinese cohort of 71 IBD patients (15 with Crohn’s disease and 56 with ulcerative colitis) and 77 healthy controls via viral-like particle (VLP) and bulk virome sequencing of their feces. By utilizing an integrated gut virus catalog tailored to the IBD virome, we revealed fundamental alterations in the gut virome in IBD patients. These characterized 139 differentially abundant viral signatures, including elevated phages predicted to infect Escherichia, Klebsiella, Enterococcus_B, Streptococcus, and Veillonella species, as well as IBD-depleted phages targeting Prevotella, Ruminococcus_E, Bifidobacterium, and Blautia species. Remarkably, these viral signatures demonstrated high consistency across diverse populations such as those in Europe and the USA, emphasizing their significance and broad relevance in the disease context. Furthermore, fecal virome transplantation experiments verified that the colonization of these IBD-characterized viruses can modulate experimental colitis in mouse models.ConclusionsBuilding upon these insights into the IBD gut virome, we identified potential biomarkers for prognosis and therapy in IBD patients, laying the foundation for further exploration of viromes in related conditions.-rW5fkHC-UvmYPog5oPfKKVideo

Primary caregiver burden and undiagnosed mental health illness in out-patients with inflammatory bowel disease-A multicentric prospective survey from the IBD Emerging Nations' Consortium.

Mental health is an overlooked aspect of inflammatory bowel disease (IBD) patient care with limited data from the developing world. The primary caregiver burden is expected to be high, but has not been evaluated. We conducted a questionnaire-based survey of consecutive out-patients with no diagnosed mental health illness (n = 289) and their primary caregivers (n = 247) from 10 centers across eight countries (Bangladesh, India, Iran, Malaysia, Myanmar, Nepal, Pakistan, Thailand) of IBD-Emerging Nations' Consortium (ENC). Patients were assessed for anxiety (PHQ-9), depression (GAD-7), quality of life (SIBDQ, IBDCOPE) and medication adherence (MMAS-8). Caregiver burden was assessed by Zarit-Burden Interview (ZBI), Ferrans and Power Quality of Life (QOL) scores and coping strategies (BRIEF-COPE). Multivariate logistic regression and correlation analyses were performed to identify risk factors and theimpact on QOL in patients and caregivers. Moderate to severe depression and anxiety were noted in 33% (severe 3.5%) and 24% (severe 3.8%) patients, respectively. The risk factor for depression was active disease (p < 0.001, OR6.3), while male gender (p = 0.01, OR0.45) and medication adherence (p = 0.003, OR0.75) were protective. Risk factors for anxiety were unmarried status (p = 0.015, OR2.3), female gender (p = 0.004, OR0.41), steroid use (p = 0.016, OR2.1) and active disease (p < 0.001, OR7.97). High GAD-7 and PHQ-9 scores positively correlated with high disease activity (r = 0.55, p < 0.001, Crohn's disease; r = 0.52, p < 0.001 ulcerative colitis) and negatively with SIBDQ (r = - 0.63, p < 0.001; r = - 0.64, p < 0.001 CD; r = 0.36, p = 0.001,UC). Sixty-five percent (159/249) primary caregivers reported high burden (ZBI ≥ 21), which positively correlated with low educational status and low-income and negatively with QOL(r = - 0.33, p < 0.001). The primary adaptive coping strategy among caregivers was religion, while maladaptive strategy was self-distraction. Nearly two-thirds of primary caregivers reported high burden of care. There was also high prevalence of undiagnosed depression and anxiety in IBD out-patients. This highlights the need for patient-caregiver integrated mental-health services in the developing world.

The Effect of Protein Nutritional Support on Inflammatory Bowel Disease and Its Potential Mechanisms.

Inflammatory bowel disease (IBD), a complex chronic inflammatory bowel disorder that includes Crohn's disease (CD) and Ulcerative Colitis (UC), has become a globally increasing health concern. Nutrition, as an important factor influencing the occurrence and development of IBD, has attracted more and more attention. As the most important nutrient, protein can not only provide energy and nutrition required by patients, but also help repair damaged intestinal tissue, enhance immunity, and thus alleviate inflammation. Numerous studies have shown that protein nutritional support plays a significant role in the treatment and remission of IBD. This article presents a comprehensive review of the pathogenesis of IBD and analyzes and summarizes the potential mechanisms of protein nutritional support in IBD. Additionally, it provides an overview of the clinical effects of protein nutritional support in IBD and its impact on clinical complications. Research findings reveal that protein nutritional support demonstrates significant benefits in improving clinical symptoms, reducing the risk of complications, and improving quality of life in IBD patients. Therefore, protein nutritional support is expected to provide a new approach for the treatment of IBD.

Micronutrient deficiencies in inflammatory bowel disease: an incidence analysis.

Micronutrient deficiencies associated with malnutrition in patients with inflammatory bowel disease (IBD) can lead to complications including anemia, coagulopathy, poor wound healing, and colorectal cancer. This study aimed to investigate micronutrient deficiencies (copper, vitamins A, B 9 , E, and K) in IBD patients and highlight associated symptoms to aid in the recognition of micronutrient deficiencies. A retrospective electronic chart review was performed on adults diagnosed with Crohn's disease or ulcerative colitis hospitalized at a tertiary care center for IBD flare between January 2013 and June 2017. Patients with serum or whole blood micronutrient levels were included. Pregnant and incarcerated patients were excluded. A total of 611 IBD patients (440 Crohn's disease, 171 ulcerative colitis) met the inclusion criteria. Micronutrients were assessed in a subset of IBD patients (copper: 12.3%, A: 10.1%, B 9 : 95.9%, E: 10.3%, and K: 4.6%). Overall, 10.1% of patients had micronutrient deficiencies. The proportion of patients with copper, A, B 9 , E, and K deficiencies were 25.4, 53.3, 1.9, 23.7, and 29.4% for Crohn's disease and 50, 52.9, 1.2, 43.8, and 18.2% for ulcerative colitis, respectively. The most common symptoms or historical features associated with micronutrient deficiency were anemia (copper, B 9 ), muscle weakness (copper, E) thrombocytopenia, fatigue (copper, B 9 ), diarrhea (B 9 ), dry skin, hyperkeratosis, pruritus, significant weight loss, elevated C-reactive protein (A), bleeding, and osteoporosis (K). Micronutrient deficiencies are common in IBD patients, yet they are not routinely assessed. Copper, vitamins A, E, and K deficiencies are particularly underrecognized. Associated historical features should raise suspicion and prompt assessment and treatment.

HIV infection is associated with a less aggressive phenotype of inflammatory bowel disease. A multicenter study of the ENEIDA registry.

The coexistence of human immunodeficiency virus (HIV) infection and inflammatory bowel disease (IBD) is uncommon. Data on the impact of HIV on IBD course and its management is scarce. To describe the IBD phenotype, therapeutic requirements and prevalence of opportunistic infections (OI) in IBD patients with a coexistent HIV infection. Case-control, retrospective study including all HIV positive patients diagnosed with IBD in the ENEIDA registry. Patients with positive HIV serology (HIV-IBD) were compared to controls (HIV seronegative), matched 1:3 by year of IBD diagnosis, age, gender and type of IBD. A total of 364 patients (91 HIV-IBD and 273 IBD controls) were included. In the whole cohort, 58% had ulcerative colitis (UC), 35% had Crohn's disease (CD) and 7% were IBD unclassified. The HIV-IBD group presented a significantly higher proportion of proctitis in UC and colonic location in CD but fewer extraintestinal manifestations than controls. Regarding treatments, non-biological therapies (37.4% vs. 57.9%; P=0.001) and biologicals (26.4% vs. 42.1%; P=0.007), were used less frequently among patients in the HIV-IBD group. Conversely, HIV-IBD patients developed more OI than controls regardless of non-biological therapies use. In the multivariate analysis, HIV infection (OR 4.765, 95%CI 2.48-9.14; P<0.001) and having ≥1 comorbidity (OR 2.445, 95%CI 1.23-4.85; P=0.010) were risk factors for developing OI, while CD was protective (OR 0.372, 95%CI 0.18-0.78;P=0.009). HIV infection appears to be associated with a less aggressive phenotype of IBD and a lesser use of non-biological therapies and biologicals but entails a greater risk of developing OI.

A prediction method for the individual serum concentration and therapeutic effect for optimizing adalimumab therapy in inflammatory bowel disease.

Adalimumab (ADM) therapy is effective for inflammatory bowel disease (IBD), but a significant number of IBD patients lose response to ADM. Thus, it is crucial to devise methods to enhance ADM's effectiveness. This study introduces a strategy to predict individual serum concentrations and therapeutic effects to optimize ADM therapy for IBD during the induction phase. We predicted the individual serum concentration and therapeutic effect of ADM during the induction phase based on pharmacokinetic and pharmacodynamic (PK/PD) parameters calculated using the empirical Bayesian method. We then examined whether the predicted therapeutic effect, defined as clinical remission or treatment failure, matched the observed effect. Data were obtained from 11 IBD patients. The therapeutic effect during maintenance therapy was successfully predicted at 40 of 47 time points. Moreover, the predicted effects at each patient's final time point matched the observed effects in 9 of the 11 patients. This is the inaugural report predicting the individual serum concentration and therapeutic effect of ADM using the Bayesian method and PK/PD modelling during the induction phase. This strategy may aid in optimizing ADM therapy for IBD.

Body-wide genetic deficiency of poly(ADP-ribose) polymerase 14 sensitizes mice to colitis.

Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract affecting millions of people. Here, we investigated the expression and functions of poly(ADP-ribose) polymerase 14 (Parp14), an important regulatory protein in immune cells, with an IBD patient cohort as well as two mouse colitis models, that is, IBD-mimicking oral dextran sulfate sodium (DSS) exposure and oral Salmonella infection. Parp14 was expressed in the human colon by cells in the lamina propria, but, in particular, by the epithelial cells with a granular staining pattern in the cytosol. The same expression pattern was evidenced in both mouse models. Parp14-deficiency caused increased rectal bleeding as well as stronger epithelial erosion, Goblet cell loss, and immune cell infiltration in DSS-exposed mice. The absence of Parp14 did not affect the mouse colon bacterial microbiota. Also, the colon leukocyte populations of Parp14-deficient mice were normal. In contrast, bulk tissue RNA-Seq demonstrated that the colon transcriptomes of Parp14-deficient mice were dominated by abnormalities in inflammation and infection responses both prior and after the DSS exposure. Overall, the data indicate that Parp14 has an important role in the maintenance of colon epithelial barrier integrity. The prognostic and predictive biomarker potential of Parp14 in IBD merits further investigation.

Eosinophils, Eosinophilic Gastrointestinal Diseases, and Inflammatory Bowel Disease: A Critical Review.

Inflammatory bowel disease (IBD) and eosinophilic gastrointestinal diseases (EGIDs) are complex, multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. Their epidemiology, particularly for eosinophilic esophagitis (EoE), is increasing worldwide, with a rise in the co-diagnosis of IBD and EGIDs. Both disorders share common risk factors, such as early exposure to antibiotics or specific dietary habits. Moreover, from a molecular perspective, eosinophilic infiltration is crucial in the diagnosis of eosinophilic disorders, and it also plays a pivotal role in IBD histological diagnosis. Indeed, recent evidence highlights the significant role of eosinophils in the health of the intestinal mucosal barrier and as mediators between innate and acquired immunity, even indicating a potential role in IBD pathogenesis. This narrative review aims to summarize the current evidence regarding the common clinical and molecular aspects of EGIDs and IBD and the current state of knowledge regarding overlap conditions and their pathogenesis. Pubmed was searched until May 2023 to assess relevant studies describing the epidemiology, pathophysiology, and therapy of EGIDs in IBD. The immune pathways and mechanisms underlying both EGIDs and IBD remain partially known. An improved understanding of the role of eosinophils in overlapping conditions could lead to enhanced diagnostic precision, the development of more effective future therapeutic strategies, and a more accurate prediction of patient response. Consequently, the identification of red flags indicative of an eosinophilic disorder in IBD patients is of paramount importance and must be evaluated on a case-by-case basis.