Risk Of Inflammatory Bowel Disease Research Articles

P1154 Mediterranean dietary approaches to stop hypertension intervention for neurodegenerative delay (MIND) diet can reduce Inflammatory Bowel Disease risk: a prospective cohort study

Abstract Background The global increasing prevalence of Inflammatory Bowel Diseases (IBD) places a substantial burden on families and society at large. The lack of a definitive cure for this chronic condition underscores the critical need for effective preventive measures. Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, emphasizing natural plant-based foods while limiting animal products and high-saturated fats, emerges as a promising dietary approach. This study aims to bridge the gap in understanding the impact of the MIND diet on IBD risk. Methods We utilized data from 187,549 participants in the UK Biobank who provided dietary information and were free of IBD at baseline. Dietary information including the consumption of over 200 common foods and 30 beverages was collected for five rounds by a validated web-based 24-hour dietary recall questionnaire. A MIND diet score was evaluated based on the intake of ten beneficial and five unhealthy food groups and was further grouped by tertiles. The outcome of interest was Crohn’s disease (CD) and ulcerative colitis (UC), ascertained via inpatient data and primary care data. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results After a mean follow-up of 10.7 years, we documented 335 and 655 incident CD and UC. The average age of the participants was 56.2 years, of which 55.0% were females. We found that greater adherence to the MIND diet, represented by higher diet score, was associated with a lower risk of CD (HR comparing extreme tertiles 0.66, 95% CI 0.50-0.89, P=0.006; P-trend=0.005) and UC (HR 0.80, 95% CI 0.65-0.98, P=0.030; P-trend=0.029) (Table 1). In the secondary analysis, we investigated the impact of fifteen individual food components in the MIND diet and found that consumption of olive oil was inversely associated with CD, and consumption of wine was inversely associated with UC. Conclusion We found higher adherence to the MIND diet was associated with lower risk of CD and UC. Our findings call for further research on the potential of the MIND diet to prevent IBD.

P149 Bacteroides uniformis ameliorates pro-inflammatory diet-exacerbated colitis by targeting endoplasmic reticulum stress-mediated ferroptosis

Abstract Background Pro-inflammatory diet is positively associated with the risk and progression of inflammatory bowel diseases. Recently, ferroptosis was observed in patients with dietary pattern-associated colitis. However, the mechanisms underlying the effects of a pro-inflammatory diet and whether it mediates ferroptosis are unknown. This study aimed to clarify the mechanisms of pro-inflammatory diet in colitis. Methods Mice were fed a dietary inflammatory index-based pro-inflammatory diet for 12 weeks. Subsequently, colitis was chemically induced using 2.5% dextran sulfate sodium with or without a ferroptosis inhibitor (ferrostatin-1). Body weight, histological scores, immune response, and mucosal barrier function were evaluated to assess intestinal inflammation.Colon tissue transcriptomics, fecal microbiome, and serum metabolomics were applied to identify diet-microbe-host interactions. Dietary inflammatory index of 36 patients with Crohn’s disease were evaluated. Their intestinal specimens were also collected. The biological functions of Bacteroides uniformis were observed in vitro and in vivo. Results Pro-inflammatory diet induced low-grade intestinal inflammation and exacerbated colitis by activating glutathione peroxidase 4-associated ferroptosis in the endoplasmic reticulum stress-mediated pathway; ferrostatin-1 treatment reversed this pro-inflammatory potential. Additionally, the pro-inflammatory diet triggered colitis by modulating the gut microbiota and metabolites. Notably, supplementation with B. uniformis improved the pro-inflammatory diet-aggravated colitis by inhibiting endoplasmic reticulum stress-mediated ferroptosis. Co-culturing B. uniformis with intestinal epithelial cells revealed it is non-enterotoxigenic and non-enteroinvasive. Conclusion Pro-inflammatory diet drives colitis by targeting endoplasmic reticulum stress-mediated ferroptosis, possibly in a gut microbiota-dependent manner. Pro-inflammatory diet restriction and microbial-based therapies may be effective strategies for preventing and treating inflammatory bowel disease.

P704 Safety of Immunosuppression in A Prospective Cohort of Inflammatory Bowel Disease Patients with a HIstoRy of CancEr: The SAPPHIRE Registry

Abstract Background For patients with inflammatory bowel disease (IBD) and a history of cancer, retrospective studies have failed to find evidence suggesting that exposure to biologic and/or immunomodulator (IMM) agents was associated with new or recurrent cancer. The SAPPHIRE Registry was developed to prospectively examine this issue. Methods Patients with IBD who had a confirmed first (index) cancer 5 years prior to enrollment were recruited from centers affiliated with the New York Crohn’s and Colitis Organization (NYCCO) since 2016. Patients receiving chemotherapy or radiation therapy at enrollment or recurrent cancer within the last five years were excluded. The primary outcome was the development of an incident cancer stratified by IBD therapy exposure and adjusted for index cancer stage, index cancer type, sex, smoking history, and age at index cancer in a Cox proportional hazards model. Results 302 patients were analyzed. Median age at IBD diagnosis was 31.5. Patients were 47% male, 88% white, and 61% never smokers. Index cancers were solid organ (138; 46%), dermatologic (100; 33%) GI (34; 11%), hematologic (27; 9%), or of other types (3; 1%); most index cancers (excluding non-melanoma skin cancer) were diagnosed as Stage 1. Following the index cancer, 90 (30%) patients were not exposed to any immunosuppression, and the other 212 were exposed to immunosuppressive therapy: 142 biologic monotherapy (anti-TNF, anti-integrin, anti-IL12/23, anti-IL23; 47%), 13 anti-metabolite monotherapy (mercaptopurine, azathioprine, methotrexate; 4%), 41 biologic + anti-metabolite combination therapy (14%), and 16 exposed to small molecules (JAK inhibitors, ozanimod; 5%). During follow-up, 46 (15%) patients developed subsequent cancers (25 new, 21 recurrent): 22 (48%) dermatologic, 15 (33%) solid, 7 (15%) GI, and 2 (4%) hematologic malignancies at a median age of 63.5. Patients not exposed to immunosuppression experienced incident cancer at a rate of 2.58/100 person-years (PY, Table). Those exposed to immunosuppression had a rate of 5.12/100 PY, representing an additional 2.54 cancers/100 PY (95% CI: 0.22, 4.85). In a time-varying Cox proportional hazards model adjusting for clinical and demographic characteristics, the adjusted hazard ratio for incident cancer for patients exposed to immunosuppressive therapy compared to unexposed patients was 1.36 (95% CI: 0.73, 2.52). Excluding non-melanoma skin cancer, the adjusted hazard ratio was 1.38 (95% CI: 0.66, 2.91). Conclusion In this ongoing prospective study, we have thus far found no association between immunosuppressive IBD therapy and risk of developing new or recurrent cancer. Ongoing enrollment and follow-up, specifically for individual drug classes and cancer types, are required to confirm these findings.

P094 Lack of DNA methyltransferase DNMT3A in fibroblasts impairs cell growth and wound healing

Abstract Background Fibrotic scarring is an untreatable pathological wound-healing complication that invalidates correct organ function. However, pathomechanisms leading to intestinal fibrosis during inflammatory bowel disease (IBD) are not fully understood. Since the de novo DNA methyltransferase DNMT3A has been associated with increased risk for IBD and alters epithelial homeostasis, we sought to characterize how DNMT3A loss might affect fibroblasts, the key mesenchymal cells involved in wound healing. Methods We stably depleted Dnmt3a in 3T3 fibroblast cell line using CRISPR-Cas9 technology and subsequently selected GFP-positive clones using FACS sorting. Cell cultures were performed in vessels with or without 0.2% gelatin coat. Reverse transcription quantitative PCR, western blot, and immunofluorescence were used to confirm Dnmt3a gene deletion and characterize wild-type (WT) and knockout cells (KO). Wound healing assays in the presence or absence of tissue repair cytokine TGF-β served to quantify and assess cell capacity of wound closure. Results 3T3 fibroblasts lacking Dnmt3a acquire an activated myofibroblast phenotype (characterized by increased α-SMA expression) that also overexpress tissue remodelling matrix metalloproteinase Mmp3, and the inflammation-induced necroptosis marker RIPK3 when compared to their WT counterparts. In addition, Dnmt3a-depleted 3T3 cells grow overlapped in tightly aggregated foci (fig. 1), and when seeded in vessels without the gelatin coat, they form spheroids. To assess healing properties, the closure of a wound (gap) in a cell monolayer was monitored. While WT 3T3 fibroblasts closed the gap within 48h, Dnmt3a KO 3T3 cells were unable to refill the empty space and formed aggregated foci in the vicinity of the wound (fig. 1). When the wound healing assay was repeated in the presence of TGF-β, WT cells nearly closed the gap within 24h whereas Dnmt3a KO 3T3 still failed to grow. Conclusion We conclude that Dnmt3a is crucial for fibroblast homeostasis and correct wound healing. Furthermore, TGF-β signalling is impaired when Dnmt3a is lacking. Thus, additional characterization of Dnmt3a depletion in fibroblasts will deepen the understanding of fibrosis and point towards new therapeutic approaches for this untreatable complication.

P364 Faecal calprotectin testing in patients presenting with lower gastrointestinal symptoms; a retrospective primary care study in the United Kingdom

Abstract Background Faecal calprotectin (FC) is of value in differentiating Inflammatory Bowel Disease (IBD) from other causes of lower gastrointestinal (GI) symptoms and is recommended in national guidance. This study aims to examine the role of and factors associated with faecal calprotectin requesting in primary care. Methods Retrospective open cohort study using Clinical Practice Research Datalink (CPRD Aurum) of adults aged 18 years and above with lower GI symptoms between 2015 and 2019. FC requested 30 days before to 3 months after a lower GI symptom record in primary care were included. Logistic regression model was used to explore patient level factors associated with FC testing. Referral pathways and outcomes in terms of IBD diagnoses of patients with and without FC testing were also examined. Results Of 741,190 symptomatic patients, only 18,320 (2.5%) patients had a FC requested in primary care: median age 38.3 (IQR 28.9-50.7); 51.4% females. The percentage of FC requests in symptomatic patients increased from 0.02% in 2010 to 4.4% in 2019 (p=0.001). FC value of <50 ug/g and 50-200 ug/g were predominantly seen in patients with abdominal pain (42.1% and 37.9% respectively) while FC > 200 ug/g was predominantly seen in patients with diarrhoea (45.3%). The only patients with a significant risk of IBD with a FC 50-200ug/g were patients with rectal bleeding (8%). Factors associated with less FC requesting included: increasing age (>70 years aOR 0.16 ( 95% CI 0.15-0.18); female (0.89,0.86-0.92); Black (0.61, 0.56-0.66) or Asian (0.75, 0.70-0.80) ethnicity; obesity (0.89,0.85-0.93); lower socioeconomic status (0.91,0.86-0.98); comorbidity score >2 (0.73,0.68-0.79); and current smoking (0.89,0.85-0.92). Patients with change in bowel habit (7.31,6.90-7.75); rectal bleeding (2.04,1.95-2.13); diarrhoea (2.88,2.78-2.99) as a presenting symptom compared to abdominal pain and ex-smokers (1.06,1.03-1.11) had more FC requests. Of patients referred with a FC >200 ug/g, 21.5% were diagnosed with IBD but only 2.9% of patients with a FC 50-200ug/g. 27.8% patients with a normal FC test result were still referred to secondary care, of which only 0.4% had IBD. Conclusion Despite an increase in FC requests in recent years, only 4.4% of patients with relevant lower GI symptoms had an FC requested in primary care as recommended. Despite a negative FC test, 27.8% of patients were still referred to secondary care with very few patients diagnosed with IBD (0.4%).

P1159 Gene and environment interactions in inflammatory bowel disease: a systematic review of human epidemiologic studies

Abstract Background Complex gene-environment interaction for Inflammatory Bowel Disease (IBD) remains elusive. This systematic review aims to summarize the current evidence of gene and environment interactions in IBD. Methods PubMed, EMBASE, Web of Science and Scopus were systematically searched from inception through July 20, 2022 to identify publications examining the interaction effect of genetic variants and environmental factors in IBD. Two investigators independently screened the title/abstract and full text according to the predefined criteria. All eligible studies were graded using STREGA guideline. The protocol was registered on PROSPERO (CRD42023443071). Results 4,305 publications were identified and screened, resulting in 36 eligible studies. 17 studies reported statistically significant interactions. The interaction effect of NOD2 and smoking was most frequently investigated and showed variant-specific interaction at rs2066847 regrading risk of Crohn’s disease (CD). Gene-smoking interactions were further identified in 1) other IBD risk genes (ATG16L1, IL23R, CALM3), as well as the IBD-genetic risk score (GRS), 2) detoxification genes (GSTP1 and ΗΜΟΧ1), 3) smoking-associated genes (CHRNA3, CHRNA5, PPP1R3C, BDNF), as well as the general smoking-GRS, and 4) the inflammation cytokine gene (IL-1β) using the candidate gene approach. Using the Illumina immune-focused Chip, another 64 smoking interacting variants were identified. Gene-diet interactions were reported across different nutritional measures, including the intake of fatty acids with CYP4F3 and FADS2, serum level of selenium with SEPHS1and SEPSECS, dietary intake of potassium with IL21, alcohol consumption with IL12B, dietary heme iron intake with FcgRIIA and serum level of 25-hydroxyvitamin D with VDR. No genome wide environment interaction studies (GWEIS) of IBD have been conducted to date, while this strategy holds great potential to unravel the missing heritability influenced by environment factors for IBD. Conclusion While past studies have increased insights into potential gene-environmental interactions in the pathophysiology of IBD, current evidence is limited and inconclusive due to lack of replication of presented results, and limited study power. Further research, including GWEIS and clinical trials, is needed for future recommendations on lifestyle and dietary modification, based on individual genetic backgrounds.

P488 Development and validation of a risk prediction tool for inflammatory bowel disease (IBD) diagnosis in patients presenting in primary care with abdominal symptoms, a UK based study

Abstract Background There are no prediction models for a diagnosis of inflammatory bowel disease (IBD) in primary care. An IBD risk prediction tool has the potential to reduce the length of time patients have undiagnosed IBD symptoms and improve IBD clinical outcomes. Therefore, our aim was to develop and validate a risk prediction model for the diagnosis of IBD, ulcerative colitis (UC) and Crohn’s disease (CD) in men and women separately. Methods A population-based retrospective open cohort study using Clinical Practice Research Datalink (CPRD) Aurum database was undertaken between 1st January 2010 and 31st December 2019, including patients aged 18 years or older. Patients were followed from first presentation with lower gastrointestinal (GI) symptoms potentially related to IBD to the earliest of IBD diagnosis, loss to follow-up, death or study end. 2,054,530 patients were in the model derivation cohort and 673,320 patients in the validation cohort. Cox proportional hazards models were used to derive separate risk equations in men and women for IBD, UC and CD. Candidate predictors included demographic factors (age, sex, smoking, body mass index, Charlson comorbidity score, loperamide use), family history of IBD, co-existing conditions (anxiety, depression, irritable bowel syndrome (IBS), haemorrhoids), extraintestinal manifestations (EIM) (mouth ulcers, ophthalmic, primary sclerosing cholangitis, dermatological), investigations (hemoglobin, mean corpuscular volume, platelets, albumin, vitamin B12, ferritin, C-reactive protein, erythrocyte sedimentation rate, calprotectin level). Measures of calibration and discrimination (C-statistic and D-statistic, higher values indicate better discrimination) were determined in men and women separately in the validation cohort at 1,2,3 and 5 years after symptom presentation. Results In the derivation cohort, 15,105 (0.7%) patients had an IBD diagnosis (10.014 UC (66.3%) and 5,088 CD (33.7%)). The IBD prediction model included 41 and 40 predictors, and the UC model 37 and 36 predictors, in women and men respectively; the CD model included 37 predictors in both men and women. C-statistics and D-statistics in men were as follows: IBD model 0.77 and 1.74; UC model: 0.81 and 1.95; and CD model: 0.77 and 1.95, respectively. Similar values were observed in women.The measures of discrimination showed that the prediction models reliably differentiated patients with and without IBD, UC and CD in both sexes. Model calibration was good, tending to overestimate at higher risk thresholds in validation cohort. Conclusion A risk model of patient demographics, symptoms and investigations performs well for IBD, UC and CD and may help in prioritising suspected IBD referrals in symptomatic subjects in primary care.

Causal linkage between type 2 diabetes mellitus and inflammatory bowel disease: an integrated Mendelian randomization study and bioinformatics analysis.

Observational studies have indicated associations between type 2 diabetes mellitus (T2DM) and both colorectal cancer (CRC) and inflammatory bowel disease (IBD). However, the underlying causality and biological mechanisms between these associations remains unclear. We conducted a bidirectional Mendelian randomization (MR) analysis employing summary statistics from genome-wide association studies involving European individuals. The inverse variance weighting (IVW) method was the primary method used to assess causality. Additionally, we applied MR Egger, Weighted median, Simple mode, and Weighted mode to evaluate the robustness of the results. Outliers were identified and eliminated using the MR-PRESSO, while the MR-Egger intercept was used to assess the horizontal pleiotropic effects of single nucleotide polymorphisms (SNPs). The heterogeneity was evaluated using the Cochrane Q test, and sensitivity analysis was performed using leave-one-out method. The F statistic was calculated to evaluate weak instrumental variable bias. Finally, a pilot bioinformatics analysis was conducted to explore the underlying biological mechanisms between T2DM and IBD/UC. The IVW results demonstrated that T2DM significantly reduced risks of IBD (OR=0.885, 95% CI: 0.818-0.958, P=0.002) and ulcerative colitis (UC) (OR=0.887, 95% CI: 0.812-0.968, P=0.007). Although the 95% CIs of MR Egger, Weighted median, Simple mode, and Weighted mode were broad, the majority of their estimates were consistent with the direction of IVW. Despite significant heterogeneity among SNPs, no horizontal pleiotropy was observed. The leave-one-out analysis showed that the causality remained consistent after each SNP was removed, underscoring the reliability of the results. Reverse MR analysis indicated that genetic susceptibility to both CRC and IBD had no significant effect on the relative risk of T2DM. Ten hub genes were identified, which mainly enriched in pathways including maturity onset diabetes of the young, thyroid cancer, gastric acid secretion, longevity regulating pathway, melanogenesis, and pancreatic secretion. The presence of T2DM does not increase the risk of CRC or IBD. Moreover, T2DM might reduce risk of IBD, including UC. Conversely, the occurrence of CRC or IBD does not influence the risk of T2DM. The association between T2DM and IBD/UC may be related to the changes in multiple metabolic pathways and CTLA-4-mediated immune response.

Overcoming cancer risk in inflammatory bowel disease: new insights into preventive strategies and pathogenesis mechanisms including interactions of immune cells, cancer signaling pathways, and gut microbiota.

Inflammatory bowel disease (IBD), characterized primarily by gastrointestinal inflammation, predominantly manifests as Crohn's disease (CD) and ulcerative colitis (UC). It is acknowledged that Inflammation plays a significant role in cancer development and patients with IBD have an increased risk of various cancers. The progression from inflammation to carcinogenesis in IBD is a result of the interplay between immune cells, gut microbiota, and carcinogenic signaling pathways in epithelial cells. Long-term chronic inflammation can lead to the accumulation of mutations in epithelial cells and the abnormal activation of carcinogenic signaling pathways. Furthermore, Immune cells play a pivotal role in both the acute and chronic phases of IBD, contributing to the transformation from inflammation to tumorigenesis. And patients with IBD frequently exhibit dysbiosis of the intestinal microbiome. Disruption of the gut microbiota and subsequent immune dysregulation are central to the pathogenesis of both IBD and colitis associated colorectal cancer (CAC). The proactive management of inflammation combined with regular endoscopic and tumor screenings represents the most direct and effective strategy to prevent the IBD-associated cancer.

A Comprehensive Global Population-Based Analysis on the Coexistence of Eosinophilic Esophagitis and Inflammatory Bowel Disease.

We explored inflammatory bowel disease (IBD) and eosinophilic esophagitis (EoE) coexistence using a global dataset. Investigating their epidemiology, risks, and impact, we aimed to enhance the understanding of concurrent diagnoses and patient outcomes. A retrospective population-based cohort study was conducted using deidentified patient data from the TriNetX database (2011-2022). We estimated the incidence and prevalence of EoE in patients with IBD, including both Crohn's disease (CD) and ulcerative colitis (UC), and vice versa. Risks of select immune-mediated conditions and disease complications were compared among patients with EoE, IBD, or concurrent diagnoses. Our results included 174,755 patients with CD; 150,774 patients with UC; and 44,714 patients with EoE. The risk of EoE was significantly higher among patients with CD (prevalence ratio [PR] 11.2) or UC (PR 8.7) compared with individuals without IBD. The risk of IBD was higher in patients with EoE (CD: PR 11.6; UC: PR 9.1) versus those without EoE. A propensity-matched analysis of IBD patients revealed that, when comparing patients with and without EoE, the relative risk of immune-mediated comorbidities was significantly greater for celiac disease, IBD-related inflammatory conditions, eczema and asthma (CD: n = 1896; UC: n = 1231; p < 0.001). Patients with a concurrent diagnosis of EoE and IBD had a higher composite risk of IBD-related complications (CD: adjusted HR (aHR) 1.14, p < 0.005; UC: aHR 1.17, p < 0.01) and lower risk of food bolus impaction (aHR 0.445, p = 0.0011). Simultaneous EoE and IBD increased IBD-related complications risk, needing more treatment (glucocorticoids, biologic therapy, abdominal surgery), while reducing EoE-related issues like food bolus impaction.

Assessment of safety profile of secukinumab in real-world scenario using United States food and drug administration adverse event reporting system database

Secukinumab is an anti-IL-17 monoclonal antibody approved for treating psoriasis and various arthritides. A comprehensive evaluation of its safety, especially in a real-world setting, is necessary. This study aimed to describe the adverse events (AE) associated with secukinumab use using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. FAERS data files containing AE reports from 2015 to 2021 were downloaded for data mining. Primary or secondary suspect medications indicated for psoriasis were identified and analyzed. Medical dictionary for regulatory activities (MedDRA version 24.1) was used to analyze the AE terms. To detect potential safety signals of AE from secukinumab use, disproportionality analysis was used. A total of 365,590 adverse event reports were identified; of these, 44,761 reports involved the use of secukinumab. Safety signals were identified for ocular infections and gastrointestinal adverse events at the standardised MedDRA query level. Safety signals for oral candidiasis, oral herpes, conjunctivitis, eye infections, and ulcerative colitis were identified at the preferred term level. The findings of our study are consistent with those of earlier studies, such as the increased risk of infections and inflammatory bowel disease. However, our study also identified additional safety signals that need to be further evaluated.

Unraveling the link between plasma caffeine concentrations and inflammatory bowel disease risk through Mendelian randomization

BackgroundCaffeine is believed to possess anti-inflammatory properties, yet direct population-based evidence regarding its impact on inflammatory bowel disease (IBD) remains scarce. ObjectivesIn this study, we used 2-sample Mendelian randomization (MR) study to investigate the causal relationship between long-term plasma caffeine concentrations and IBD and its subtypes, ulcerative colitis (UC) and Crohn disease (CD). MethodsWe used single nucleotide polymorphisms (SNPs) associated with plasma caffeine concentrations at genome-wide significance within a ±100-kb range around the CYP1A2 or AHR genes as instrumental variables. Genome-wide association study (GWAS) data for IBD and its subtypes were obtained from FinnGen and International Inflammatory Bowel Disease Genetics Consortium. We conducted a meta-analysis of MR-related SNPs from both sources and used a multiplicative inverse variance–weighted random effects model to combine the effects of each SNP proxy on exposure to outcomes. ResultsIn our study, genetically predicted higher plasma caffeine concentrations were associated with a lower risk of IBD, with an odds ratio (OR) of 0.78 (95% confidence interval [CI]: 0.66, 0.91; PFDR = 0.004). This trend was also observed in UC and CD, with ORs of 0.79 (95% CI: 0.66, 0.94; PFDR = 0.014) and 0.78 (95% CI: 0.62, 0.98; PFDR = 0.032), respectively. ConclusionOur study indicates a potential causal link between genetically predicted higher plasma caffeine concentrations and a reduced risk of IBD, including its subtypes UC and CD.

Lactobacillus plantarum MH-301 as an effective adjuvant to isotretinoin in the treatment of acne vulgaris: a randomized and open-label trail.

Acne vulgaris is a common chronic inflammatory skin disease originating in the sebaceous gland units of the skin follicles. Isotretinoin is presently the primary choice for the treatment of acne vulgaris. However, it could induce several adverse reactions like diarrhea, cheilitis, headache, elevated triglyceride levels and risk of inflammatory bowel disease and depression. Hence, it is imperative to seek an alternative therapy. One hundred five patients were randomly divided into 3 groups, and received a baseline treatment of oral doxycycline for the initial 4 weeks. Group I received isotretinoin oral for 12 weeks; Group P received oral Lactobacillus plantarum MH-301 treatment for 12 weeks; Group IP received combined treatment with oral probiotics and oral isotretinoin for 12 weeks. The number of skin lesions was recorded at 0, 4, 8, and 12 weeks during the treatment to compare the efficacy of each intervention, and skin and fecal samples were collected from patients at 12 weeks for high-throughput sequencing to explore the microbiota differences between various groups. Our results revealed that the combination of L. plantarum MH-301 with isotretinoin significantly reduced the number of skin lesions in patients compared to using L. plantarum MH-301 and isotretinoin alone (p < 0.001). Additionally, skin microbiome High-throughput analysis indicated the restorative effects of L. plantarum MH-301 on skin microbial diversity while also observing a reduction in the main microbiota of skin lesions, Propionibacterium and Corynebacterium. Meanwhile, gut microbiome High-throughput analysis showed that it could regulate disorders of the intestinal microbiota and increased the abundance of probiotics such as Lactobacillus, Bifidobacterium, Coprococcus and Bacteroides genera. In conclusion, L. plantarum MH-301 could be used in combination with isotretinoin for optimal results in the treatment of acne vulgaris. The research conducted provides theoretical and data support for the adjuvant effect of L. plantarum in the treatment of acne vulgaris. [ClinicalTrials.gov], identifier (ChiCTR2200063499).

Dietary Patterns and Risk of Inflammatory Bowel Disease: A Systematic Review of Observational Studies.

The incidence of inflammatory bowel disease (IBD) is increasing worldwide. Dietary patterns may be associated with odds of this disease. Although previous reviews have attempted to summarize the evidence in this field, the growing body of investigations prompted us to conduct an updated comprehensive systematic review. We used the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to evaluate the association between dietary patterns before disease onset and the risk of IBD. PubMed, SCOPUS, and Web of Science were searched using structured keywords up to November 20, 2023. Twenty-four publications (13 case-control, 1 nested case-control, and 10 cohort studies) were included in this review. The sample size of these studies ranged from 181 to 482 887 subjects. The findings were inconsistent across the included studies, showing inverse, direct, or no association between different dietary patterns and the risk of IBD. This review provides comprehensive data on the link between dietary patterns prior to IBD diagnosis and risk of this condition. The explicit finding of present review is the extent gap in our knowledge in this field. Therefore, large-scale, high-quality studies are warranted to improve our understanding of the relationship between dietary patterns and IBD risk.

Early-life diet and risk of inflammatory bowel disease: a pooled study in two Scandinavian birth cohorts

ObjectiveWe assessed whether early-life diet quality and food intake frequencies were associated with subsequent IBD.DesignProspectively recorded 1-year and 3-year questionnaires in children from the All Babies in Southeast Sweden and...

The association between circulating leukocytes and inflammatory bowel disease: a two-sample Mendelian randomization study.

Inflammatory bowel disease (IBD) is a highly prevalent, recurrent, chronic intestinal inflammatory disease. Several observational studies have shown that circulating leukocytes are strongly associated with IBD. However, whether alterations in leukocytes are causally related to IBD remains uncertain. The present study explores this issue with the Mendelian randomization (MR) analysis method. The Genome wide association study (GWAS) statistical data related to circulating leukocytes and IBD were obtained from the Blood Cell Consortium and the IEU Qpen GWAS project, respectively. Inverse variance weighting (IVW) was used as the main MR analytical method, coupled with a series of sensitivity analyses to ensure the reliability of the results. The results of IVW showed that increased monocyte count (especially CD14- CD16+ monocyte absolute counts) was negatively correlated with the risk of IBD and its main subtypes. Increased neutrophil count was positively associated with the risk of IBD and ulcerative colitis. Meanwhile, there was no causal relationship between basophil, eosinophil, lymphocyte counts and IBD risk. These results indicate that a causal relationship exists between circulating leukocytes and the risk of IBD and its subtypes, which confirms the important role that the leukocyte immune system plays in IBD. Our findings provide additional research directions for the clinical prevention and treatment of IBD.

Greater adherence to the Mediterranean Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet is associated with lower risk of inflammatory bowel disease: a prospective cohort study.

Background: The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet is emerging as a promising candidate for preventive measures against inflammatory bowel disease (IBD), though there is currently no direct evidence from population-based studies. This study aims to bridge the gap in understanding of the association of the MIND diet with IBD risk. Methods: We utilized data from 187 490 participants in the UK Biobank who provided dietary information and were free of IBD at baseline. Dietary information was obtained using a validated web-based 24-hour dietary recall questionnaire. A MIND diet score was evaluated based on the intake of ten beneficial and five unhealthy food groups and the scores were further grouped into tertiles. The outcome of interest was incident IBD, Crohn's disease (CD), and ulcerative colitis (UC). Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models adjusted for demographic characteristics, lifestyle factors, cancer history, and other dietary factors. Mediation analyses were performed to evaluate the role of systemic inflammation and metabolic disorders represented by the integrated biomarkers in the MIND diet-IBD association. Results: After a mean follow-up of 10.7 years, we documented 825 incident IBD cases (250 CD and 575 UC). The average age of the participants was 56.2 years, of which 55.0% were females. We found that greater adherence to the MIND diet, represented by a higher diet score, was associated with a lower risk of IBD (HRcomparing extreme tertiles 0.74, 95% CI 0.62-0.90, p = 0.002; p for trend = 0.005), CD (HR 0.66, 95% CI 0.47-0.94, p = 0.022; p for trend = 0.023), and UC (HR 0.78, 95% CI 0.62-0.98, p = 0.031; p for trend = 0.022). The associations were partially mediated by metabolic and inflammation status (mediation proportion: 5.5-15.9%). Conclusion: We found higher adherence to the MIND diet was associated with a lower risk of IBD, and that inflammatory and metabolic conditions may play an important role in the underlying mechanistic pathways.

The Causal Relationship between Immune-Mediated Inflammatory Diseases and Aortic Aneurysm: A Bidirectional Two-Sample Mendelian Randomization Study.

We sourced genetic association data from public genome-wide association study databases for populations of European ancestry. Adhering to MR principles, we identified valid instrumental variables from genetic variants. A range of statistical methods were applied for MR analysis, with the inverse variance weighted (IVW) method emerging as the most reliable estimator of causality in this context. The causal estimates obtained using the IVW method revealed a significant association between genetically predicted AA and rheumatoid arthritis (RA; OR = 1.06, 95% CI = 1.01-1.12, P=0.029). Conversely, genetically predicted RA showed nonsignificant causal estimates of AA (OR = 0.97, 95% CI = 0.92-1.02, P=0.204). Additionally, there was no evidence to suggest that AA may increase the risk of inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE), and psoriasis (PSO). The sensitivity analysis confirmed the absence of heterogeneity or horizontal pleiotropy effects. Our findings shed light on the causal effects between genetically predisposed AA and RA. They also suggest the potential clinical utility of human leukocyte antigen (HLA) risk genetic markers for developing personalized treatment and prevention strategies.

NLRP3 Inflammasome and Gut Dysbiosis Linking Diabetes Mellitus and Inflammatory Bowel Disease.

Diabetes mellitus and inflammatory bowel disease are chronic conditions with significant overlap in their pathophysiology, primarily driven by chronic inflammation. Both diseases are characterized by an aberrant immune response and disrupted homeostasis in various tissues. However, it remains unclear which disease develops first, and which one contributes to the other. Diabetes mellitus increases the risk of inflammatory bowel disease and inflammatory bowel disease may increase the risk of developing diabetes. This review focuses on comprehensively discussing the factors commonly contributing to the pathogenesis of diabetes mellitus and inflammatory bowel disease to draw a relationship between them and the possibility of targeting common factors to attenuate the incidence of one if the other is present. A key player in the intersection of diabetes mellitus and inflammatory bowel disease is the NLRP3 inflammasome, which regulates the production of pro-inflammatory cytokines leading to prolonged inflammation and tissue damage. Additionally, toll-like receptors via sensing microbial components contribute to diabetes mellitus and inflammatory bowel disease by initiating inflammatory responses. Gut dysbiosis, a common link in both diseases, further intensifies inflammation and metabolic dysfunction. Alterations in gut microbiota composition affect intestinal permeability and immune modulation, perpetuating a vicious cycle of inflammation and disease progression by changing protein expression. The overlap in the underlying inflammatory mechanisms has led to the potential of targeting mediators of chronic inflammation using anti-inflammatory drugs and biologics that benefit both conditions or attenuate the incidence of one in the presence of the other.

The relationship between inflammatory bowel disease and sarcopenia-related traits: a bidirectional two-sample mendelian randomization study.

Observational studies have revealed a link between inflammatory bowel disease (IBD) and sarcopenia. However, it remains unclear whether this correlation between IBD and sarcopenia is causal. The genetic instrumental variables (IVs) associated with IBD and sarcopenia-related traits were derived from publicly available genome-wide association studies. We employed a two-sample bidirectional Mendelian randomization (MR) method. we obtained genetic IVs for five phenotypes from 34,652 cases in IBD, 27,432 cases in ulcerative colitis (UC), 212356 cases in crohn's disease (CD), 9336415 cases in low hand grip strength (LHGS), and 450243 cases in appendicular lean mass (ALM), respectively. The inverse variance weighting and other MR methods were used to explore the bidirectional causal relationship. Furthermore, we performed heterogeneity test, pleiotropy test, leave-one-out sensitivity test, and multivariate MR to evaluate the robustness of the results. The forward MR results showed that the UC (OR=0.994, 95% CI: 0.9876-0.9998, P = 0.044) and CD (OR=0.993, 95% CI: 0.988-0.998, P = 0.006) was negatively correlated with ALM. In the reverse MR analysis, we also found that LHGS was negatively correlated with the IBD (OR=0.76, 95% CI: 0.61-0.94, P = 0.012) and CD (OR=0.53, 95% CI: 0.40-0.70, P <0.001). Besides, genetically predicted higher ALM reduced IBD (OR=0.87, 95% CI: 0.79-0.95, P = 0.002), UC (OR=0.84, 95% CI: 0.76-0.93, P = 0.001), and CD (OR=0.87, 95% CI: 0.77-0.99, P = 0.029). However, the results of other MR Analyses were not statistically different. We found genetically predicted UC and CD are causally associated with reduced ALM, and higher hand grip strength reduced IBD and CD risk, and higher ALM reduced IBDs risk. This MR study provides moderate evidence for a bidirectional causal relationship between IBD and sarcopenia.