Chronic gastrointestinal disorders such as inflammatory bowel diseases (IBDs) and irritable bowel syndrome (IBS) impose significant health burdens globally. IBDs, encompassing Crohn’s disease and ulcerative colitis, are multifactorial disorders characterized by chronic inflammation of the gastrointestinal tract. On the other hand, IBS is one of the principal gastrointestinal tract functional disorders and is characterized by abdominal pain and altered bowel habits. Although the precise etiopathogenesis of these disorders remains unclear, mounting evidence suggests that non-coding RNA molecules play crucial roles in regulating gene expression associated with inflammation, apoptosis, oxidative stress, and tissue permeability, thus influencing disease progression. miRNAs have emerged as possible reliable biomarkers, as they can be analyzed in the biological fluids of patients at a low cost. This review explores the roles of miRNAs in IBDs and IBS, focusing on their involvement in the control of disease hallmarks. By an extensive literature review and employing bioinformatics tools, we identified the miRNAs frequently studied concerning these diseases. Ultimately, specific miRNAs could be proposed as diagnostic biomarkers for IBDs and IBS. Their ability to be secreted into biofluids makes them promising candidates for non-invasive diagnostic tools. Therefore, understanding molecular mechanisms through the ways in which they regulate gastrointestinal inflammation and immune responses could provide new insights into the pathogenesis of IBDs and IBS and open avenues for miRNA-based therapeutic interventions.

Vedolizumab (VDZ) is used for treating inflammatory bowel disease (IBD) patients. A study investigating colonic epithelial barrier function ex vivo following VDZ is lacking. This work aims to evaluate ex vivo the colonic epithelial barrier function in IBD patients at baseline and during VDZ treatment, and to investigate the relationships between barrier function and clinical parameters. Colonic specimens were obtained from 23 IBD patients before, and at 24 and 52 weeks after VDZ treatment, and from 26 healthy volunteers (HV). Transepithelial electrical resistance (TEER, permeability to ions) and paracellular permeability were measured in Ussing chambers. IBD patients showed increased epithelial permeability to ions (TEER, 13.80 ± 1.04 Ω × cm² vs. HV 20.70 ± 1.52 Ω × cm², p < 0.001) without changes in paracellular permeability of a 4 kDa probe. VDZ increased TEER (18.09 ± 1.44 Ω × cm², p < 0.001) after 52 weeks. A clinical response was observed in 58% and 25% of patients at week 24, and in 62% and 50% at week 52, in ulcerative colitis and Crohn’s disease, respectively. Clinical and endoscopic scores were strongly associated with TEER. TEER < 14.65 Ω × cm² predicted response to VDZ (OR 11; CI 2–59). VDZ reduces the increased permeability to ions observed in the colonic epithelium of IBD patients before treatment, in parallel to a clinical, histological (inflammatory infiltrate), and endoscopic improvement. A low TEER predicts clinical response to VDZ therapy.

Growing evidence suggests that impaired gut permeability and gut microbiota alterations are involved in the pathogenesis of Inflammatory Bowel Diseases (IBDs), which include Ulcerative Colitis (UC) and Crohn’s Disease (CD). Vedolizumab is an anti-α4β7 antibody approved for IBD treatment, used as the first treatment or second-line therapy when the first line results in inadequate effectiveness. The aim of this study is to develop a mathematical model capable of describing the pathophysiological mechanisms of Vedolizumab treatment in IBD patients. In particular, the relationship between drug concentration in the blood, colonic mucosal permeability and fecal microbiota composition was investigated and modeled to detect and predict trends in order to support and tailor Vedolizumab therapies. To pursue this aim, clinical data from a pilot study on a cluster of 11 IBD patients were analyzed. Enrolled patients underwent colonoscopy in three phases (before ($t_0$), after 24 weeks of ($t_1)$ and after 52 weeks of ($t_{2 }$) Vedolizumab treatment) to collect mucosal biopsies for transepithelial electrical resistance (TEER) evaluation (permeability to ions), intestinal permeability measurement and histological analysis. Moreover, fecal samples were collected for the intestinal microbiota analysis at the three time points. The collected data were compared to those of 11 healthy subjects at $t_0$, who underwent colonoscopy for screening surveillance, and used to implement a three-compartmental mathematical model (comprising central blood, peripheral blood and the intestine). The latter extends previous evidence from the literature, based on the regression of experimental data, to link drug concentration in the peripheral blood compartment with Roseburia abundance and intestinal permeability. The clinical data showed that Vedolizumab treatment leads to an increase in TEER and a reduction in intestinal permeability to a paracellular probe, improving tissue inflammation status. Microbiota analysis showed increasing values of Roseburia, albeit not statistically significant. This trend was adequately reproduced by the mathematical model, which offers a useful tool to describe the pathophysiological effects of Vedolizumab therapy on colonic mucosal permeability and fecal microbiota composition. The model’s satisfactory predictive capabilities and simplicity shed light on the relationship between the drug, the microbiota and permeability and allow for its straightforward extension to diverse therapeutic conditions.

The biliary tract, long considered a sterile environment, is now recognized to harbor a resident microbiota with important implications for health and disease. This review aims to summarize current knowledge on the composition and function of the biliary microbiota in physiological conditions, and its alterations in pathological states such as infection and lithiasis, with a particular focus on antimicrobial resistance. In healthy individuals, the biliary microbiota appears to be shaped by bile acids and gut–bile axis interactions, playing a role in local immune modulation. In disease, microbial dysbiosis contributes to conditions such as acute cholecystitis, cholangitis, and gallstone formation, with distinct microbial signatures linked to specific stone types. Common biliary pathogens, including E. coli, Enterococcus spp., Pseudomonas spp., and K. pneumoniae, often exhibit concerning resistance patterns, impacting therapeutic strategies. Emerging evidence highlights the interplay between intestinal and biliary microbiota, suggesting potential diagnostic and prognostic applications. Understanding these dynamics opens new avenues for microbiota-informed antibiotic stewardship, targeted microbiota modulation, and precision medicine approaches. Further research, particularly culture-independent and longitudinal studies, is crucial to fully elucidate the clinical significance of the biliary microbiota and to integrate microbiota profiling into patient management strategies.