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Background/Objectives: Vitamin D (VD) has immunoregulatory properties, generating interest in its potential to influence therapeutic outcomes in inflammatory bowel disease (IBD), other than affecting the expression of genes encoding enzymes and transporters involved in drug metabolism and transport. This study investigated VD-related single nucleotide polymorphisms (SNPs) as predictors of clinical responses in patients with Crohn's disease (CD) and ulcerative colitis (UC) treated with vedolizumab (VDZ) or ustekinumab (UST) after 3 (T3) and 12 months (T12), as well as the achievement of fecal calprotectin (FC) levels < 250 mg/kg, a marker of mucosal healing. Methods: In this prospective study, 103 patients (67 CD, 36 UC) were enrolled, 40 receiving VDZ and 63 receiving UST. SNPs in the genes CYP24A1, GC, CYP27B1, and VD receptor (VDR) were analyzed via polymerase chain reaction (PCR) and associated with clinical and laboratory outcomes. Results: UST therapy demonstrated a higher clinical response rate at T12 compared to VDZ (p = 0.03). A correlation was found between response at T3 and T12 (p = 0.0002). GC 1296 AC polymorphism negatively predicted response at T12, with 63.6% of non-responders carrying this genotype. CYP24A1 8620 AG was a negative predictor for achieving FC < 250 mg/kg (p = 0.045). CYP24A1 22776 CT and VDR Cdx2 GG increased the likelihood of presenting CD over UC (OR 3.40, p = 0.009 and OR 3.74, p = 0.047, respectively). Additionally, CYP27B1 −1260 GT and +2838 CT increased the likelihood of non-ileal CD (OR 3.13, p = 0.054; OR 7.02, p = 0.01). Conclusions: This study reveals associations between VD-SNPs, clinical response to VDZ and UST, and IBD phenotype and localization, supporting the development of personalized IBD treatment and warranting further validation. [ABSTRACT FROM AUTHOR]

Changes in the gut microbiome have been associated with inflammatory bowel disease. A protective role of short chain fatty acids produced by the gut microbiota has been suggested as a causal mechanism. Nevertheless, multi-omic analyses have failed to identify a clear link between changes in specific taxa and disease states. Recently, metagenomic analyses unveiled that gut bacterial species have a previously unappreciated genomic diversity, implying that a geno-centric approach may be better suited to identifying the mechanisms involved. Here, we quantify the abundance of terminal genes in propionate-producing fermentative pathways in the microbiome of a large cohort of healthy subjects and patients with inflammatory bowel disease. The results show that propionate kinases responsible for propionate production in the gut are depleted in patients with Crohn's disease. Our results also indicate that changes in overall species abundances do not necessarily correlate with changes in the abundances of metabolic genes, suggesting that these genes are not part of the core genome. This, in turn, suggests that changes in strain composition may be as important as changes in species abundance in alterations of the gut microbiome associated with pathological conditions. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a relapsing chronic disorder of the gastrointestinal tract characterized by disruption of epithelial barrier function and excessive immune response to gut microbiota. The lack of biomarkers providing early diagnosis or defining the status of the pathology difficulties an accurate assessment of the disease. Given the different metabolomic profiles observed in IBD patients, metabolomics may reveal prime candidates to be studied, which may help in understanding the pathology and identifying novel therapeutic targets. In this review, we summarize the most current advances describing the promising metabolites such as lipids or amino acids found through untargeted metabolomics from serum, faecal, urine and biopsy samples. [ABSTRACT FROM AUTHOR]

In patients with inflammatory bowel diseases (IBD) undergoing biologic therapy, biomarkers of treatment response are still scarce. This study aimed to evaluate whether serum zonulin, a biomarker of intestinal permeability; soluble CD163 (sCD163), a macrophage activation marker; and a panel of serum cytokines could predict the response to biologic treatment in patients with IBD. For this purpose, we prospectively enrolled 101 patients with IBD and 19 patients with irritable bowel syndrome (IBS) as a control group; 60 out of 101 patients underwent treatment with biologics. Zonulin, sCD163, and cytokines were measured at the baseline in all patients and after 10 weeks of treatment in the 60 patients who underwent biologic therapy. We observed that zonulin levels were higher in IBD patients with active disease compared to those in remission (p = 0.035), and that sCD163 values were higher in patients with IBD compared to those with IBS (p = 0.042), but no association with therapy response was observed for either biomarker. Conversely, interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha showed a significant reduction from baseline to week 10 of treatment, particularly in responder patients. By multivariate logistic regression analysis corrected for disease (Crohn's disease or ulcerative colitis), type of biologic drug (Infliximab, Adalimumab, Vedolizumab, or Ustekinumab) and disease activity, the reduction in IL-6 values was associated with a clinical response at 12 months of biological therapy (odds ratio (OR) = 4.75, 95% confidence interval (CI) 1.25–18.02, p = 0.022). In conclusion, the measurement of serum IL-6 in biologics-treated IBD patients may allow for the prediction of response to treatment at 12 months of therapy and thus may help with tailoring personalized treatment strategies. [ABSTRACT FROM AUTHOR]