From serum metabolites to the gut: revealing metabolic clues to susceptibility to subtypes of Crohn's disease and ulcerative colitis.

Background and aims: Inflammatory bowel disease (IBD) is a common chronic inflammatory bowel disease characterized by diarrhea and abdominal pain. Recently human metabolites have been found to help explain the underlying biological mechanisms of diseases of the intestinal system, so we aimed to assess the causal relationship between human blood metabolites and susceptibility to IBD subtypes. Methods: We selected a genome-wide association study (GWAS) of 275 metabolites as the exposure factor, and the GWAS dataset of 10 IBD subtypes as the outcome, followed by univariate and multivariate analyses using a two-sample Mendelian randomization study (MR) to study the causal relationship between exposure and outcome, respectively. A series of sensitivity analyses were also performed to ensure the robustness of the results. Results: A total of 107 metabolites were found to be causally associated on univariate analysis after correcting for false discovery rate (FDR), and a total of 9 metabolites were found to be significantly causally associated on subsequent multivariate and sensitivity analyses. In addition we found causal associations between 7 metabolite pathways and 6 IBD subtypes. Conclusion: Our study confirms that blood metabolites and certain metabolic pathways are causally associated with the development of IBD subtypes and their parenteral manifestations. The exploration of the mechanisms of novel blood metabolites on IBD may provide new therapeutic ideas for IBD patients.

Antioxidant insights: investigating the protective role of oxidative balance in inflammatory bowel disease.

Background: Limited studies have investigated the relationship between systemic oxidative stress and inflammatory bowel disease (IBD). The purpose of this study was to explore the relationship between oxidative balance score (OBS) and IBD. Methods: We included 175,808 participants from the UK Biobank database from 2006 to 2010. OBS scores were calculated based on 22 lifestyle and dietary factors. Multiple variable Cox proportional regression models, as well as gender stratification and subgroup analysis, were utilized to investigate the relationship between OBS and IBD. Results: There is a significant negative correlation between OBS and the occurrence of IBD, ulcerative colitis (UC), and Crohn's disease (CD). Additionally, OBS is significantly negatively correlated with intestinal obstruction in CD patients. Gender stratified analysis suggest a significant correlation between OBS and CD in female patients, particularly pronounced in those under 60 years old. Sensitivity analysis indicates a significant negative correlation between lifestyle-related OBS and diet-related OBS with the occurrence of CD in females, diet-related OBS is negatively correlated with CD in males. Conclusion: OBS showed a significant negative correlation with IBD, especially in female CD patients. This study underscores the importance of antioxidant diet and lifestyle, which may provide a greater advantage for female CD patients.

Oxidative balance score: a potential tool for reducing the risk of colorectal cancer and its subsites incidences.

Background: The Oxidative Balance Score (OBS) is commonly used to assess oxidative stress and provides a comprehensive evaluation of dietary and lifestyle-related exposures. However, there is limited research on the association between OBS and colorectal cancer (CRC), its subsites, and complications. The objective of this study was to assess the relationship between OBS and the risk of CRC, its subsites, and common complications in a large prospective cohort study. Methods: We included data from 175,808 participants in the UK Biobank data sample repository from 2006 to 2010. We evaluated OBS using a scoring system based on 22 dietary and lifestyle factors. Multiple adjustments, including multivariate Cox proportional hazard regression, gender stratification, subgroup analysis, and sensitivity analysis, were performed to fully explore the relationship between OBS and CRC, its subsites, and complications. The mediation analysis was conducted to investigate whether serum albumin, uric acid, and neutrophil levels mediate the relationship between OBS and CRC. Results: After adjusting for potential confounding factors, a significant negative correlation was found between OBS and the risk of CRC and its subsites (proximal colon cancer, distal colon cancer, and rectal cancer). This correlation was particularly pronounced in male CRC patients. Serum albumin, uric acid, and neutrophil count, which are biomarkers, were found to have a significant mediating effect between OBS and CRC. Conclusion: Our study suggests that higher exposure to antioxidants assessed through OBS (diet and lifestyle rich in antioxidants) may decrease the occurrence of CRC and its subsites.

Exploring the intestinal ecosystem: from gut microbiota to associations with subtypes of inflammatory bowel disease.

Objective: Significant differences have been discovered between subtypes of Crohn's disease (CD) and ulcerative colitis (UC). The role of gut microbiota in promoting the onset of UC and CD is established, but conclusions regarding subtype-specific analyses remain limited. Methods: This study aims to explore the influence of gut microbiota on subtypes of UC and CD, offering novel insights into the pathogenesis and treatment of UC and CD.Two-sample Mendelian randomization (MR) analysis was employed to examine the causal relationship between subtypes of UC and CD and gut microbiota composition. Gut microbiota data were sourced from the International Consortium MiBioGen, while UC and CD data were obtained from FINNGEN. Eligible single nucleotide polymorphisms (SNPs) were selected as instrumental variables. Multiple analytical approaches such as inverse variance-weighted (IVW), MR-Egger regression, weighted median, weighted mode, and MR-RAPS were utilized. Sensitivity analyses including MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were conducted for quality control. Subsequently, we employed multivariable IVW, MR-Egger, weighted median, and LASSO regression methods to identify independently significant genera or families and conducted sensitivity analyses. Results: We have determined that Hungatella, Acidaminococcaceae, and 15 other microbial taxa act as protective factors for various CD and UC subtypes, while Terrisporobacter, Anaerostipes, and 23 other microbial taxa are associated with increased risk for different CD and UC subtypes. Furthermore, through multivariable MR analysis, we have identified significant genera or families with independent effects. Conclusion: Our study confirms a causal relationship between dysbiosis of gut microbiota and the occurrence of CD and UC subtypes. Furthermore, it validates etiological distinctions among different subtypes of CD and UC. A novel approach to adjunctive therapy involving distinct UC or CD subtypes may involve the use of probiotics and represents a potential avenue for future treatments.