The management of patients with inflammatory bowel disease (IBD) aims to control inflammation through the use of immunosuppressive treatments that target various points in the inflammatory cascade. However, the efficacy of these therapies in the long term is limited, and they often are associated with severe side effects. Although the pathophysiology of the disease is not completely understood, IBD is regarded as a multifactorial disease that occurs due to an inappropriate immune response in genetically susceptible individuals. The gut microbiome is considered one of the main actors in the development of IBD. Gut dysbiosis, characterised by significant changes in the composition and functionality of the gut microbiota, often leads to a reduction in bacterial diversity and anti-inflammatory anaerobic bacteria. At the same time, bacteria with pro-inflammatory potential increase. Although changes in microbiome composition upon biological agent usage have been observed, their role as biomarkers is still unclear. While most studies on IBD focus on the intestinal bacterial population, recent studies have highlighted the importance of other microbial populations, such as viruses and fungi, in gut dysbiosis. In order to modulate the aberrant immune response in patients with IBD, researchers have developed therapies that target different players in the gut microbiome. These innovative approaches hold promise for the future of IBD treatment, although safety concerns are the main limitations, as their effects on humans remain unknown.

The limited efficacy of the currently available medical therapies in a proportion of patients with Crohn’s disease has led to the research and development of molecules that can block new inflammatory pathways. Ustekinumab is a fully human IgG1 monoclonal antibody which targets the common p40 subunit of the cytokines interleukin-12 as well as interleukin-23. Consequently, the Th1 and Th17 inflammatory responses are inhibited. Ustekinumab has been recently approved for its use in patients with Crohn’s disease. Its efficacy and safety was initially proved in patients with psoriasis and psoriatic arthritis. More recently, three Phase III trials have confirmed its efficacy in patients with Crohn’s disease refractory to anti-tumor necrosis factor therapy. This biologic agent appears safe, with no increased risk of infectious or malignant complications, and a low immunogenic profile.

Background: Data on ustekinumab and vedolizumab in the elderly inflammatory bowel disease (IBD) population are limited. The aim of the current study was to assess the safety and effectiveness of both in an elderly real-life population. Methods: A multicentric retrospective study was performed on IBD patients who started vedolizumab or ustekinumab between 2010 and 2020. Clinical and endoscopic remission rates and (serious) adverse events (AE) were assessed. Results: A total of 911 IBD patients were included, with 171 (19%) aged above 60 (111 VDZ, 60 UST). Elderly patients treated with vedolizumab or ustekinumab had an increased risk for non-IBD hospitalization (10.5% vs. 5.7%, p = 0.021) and malignancy (2.3% vs. 0.5%, p = 0.045) compared to the younger population. Corticosteroid-free clinical (50% vs. 44%; p = 0.201) and endoscopic remission rates (47.9% vs. 31%, p = 0.07) at 1 year were similar. Comparing vedolizumab to ustekinumab in the elderly population, corticosteroid-free (47.9% vs. 31%, p = 0.061) and endoscopic remission rates (66.7% vs. 64.4%, p = 0.981) were similar. Vedolizumab- and ustekinumab-treated patients had comparable infection rates (13.5% vs. 10.0%, p = 0.504), IBD flare-ups (4.5% vs. 5%, p = 1.000), the occurrence of new EIMs (13.5% vs. 10%, p = 0.504), a risk of intestinal surgery (5.4% vs. 6.7%, p = 0.742), malignancy (1.8% vs. 3.3%, p = 0.613), hospitalization (9.9% vs. 11.7%, p = 0.721), and mortality (0.9% vs. 1.7%, p = 1.000). AE risk was associated only with corticosteroid use. Conclusions: Ustekinumab and vedolizumab show comparable effectiveness and safety in the elderly IBD population. Elderly IBD patients have an increased risk for non-IBD hospitalizations and malignancy compared to the younger IBD population, with corticosteroid use as the main risk factor.

Overexpression of the transmembrane mucin MUC13, as seen in inflammatory bowel diseases (IBD), could potentially impact barrier function. This study aimed to explore how inflammation-induced MUC13 disrupts epithelial barrier integrity by affecting junctional protein expression in IBD, thereby also considering the involvement of MUC1. RNA sequencing and permeability assays were performed using LS513 cells transfected with MUC1 and MUC13 siRNA and subsequently stimulated with IL-22. In vivo intestinal permeability and MUC13-related signaling pathways affecting barrier function were investigated in acute and chronic DSS-induced colitis wildtype and Muc13^−/− mice. Finally, the expression of MUC13, its regulators and other barrier mediators were studied in IBD and control patients. Mucin knockdown in intestinal epithelial cells affected gene expression of several barrier mediators in the presence/absence of inflammation. IL-22-induced MUC13 expression impacted barrier function by modulating the JAK1/STAT3, SNAI1/ZEB1 and ROCK2/MAPK signaling pathways, with a cooperating role for MUC1. In response to DSS, MUC13 was protective during the acute phase whereas it caused more harm upon chronic colitis. The pathways accounting for the MUC13-mediated barrier dysfunction were also altered upon inflammation in IBD patients. These novel findings indicate an active role for aberrant MUC13 signaling inducing intestinal barrier dysfunction upon inflammation with MUC1 as collaborating partner.

Intestinal ultrasound (IUS) has gained popularity as a first line technique for the diagnosis and monitoring of patients with inflammatory bowel diseases (IBD) due to its many advantages. It is a non-invasive imaging technique with non-ionizing radiation exposure. It can be easily performed not only by radiologists but also by trained gastroenterologists at outpatient clinics. In addition, the cost of IUS equipment is low when compared with other imaging techniques. IUS is an accurate technique to detect inflammatory lesions and complications in the bowel in patients with suspected or already known Crohn’s disease (CD). Recent evidence indicates that IUS is a convenient and accurate technique to assess extension and activity in the colon in patients with ulcerative colitis (UC), and can be a non-invasive alternative to endoscopy. In patients with IBD, several non-specific pathological ultrasonographic signs can be identified: bowel wall thickening, alteration of the bowel wall echo-pattern, loss of bowel stratification, increased vascularization, decreased bowel peristalsis, fibro-fatty proliferation, enlarged lymph nodes, and/or abdominal free fluid. Considering the transmural CD inflammation, CD complications such as presence of strictures, fistulae, or abscesses can be detected. In patients with UC, where inflammation is limited to mucosa, luminal inflammatory ultrasonographic changes are similar to those of CD. As the technique is related to the operator’s experience, adequate IUS training, performance in daily practice, and a generalized use of standardized parameters will help to increase its reproducibility.

Background: The intestinal mucosal barrier plays an important role in the pathophysiology of inflammatory bowel disease (IBD), with mucins being key components of this barrier. Classified as either transmembrane or secreted, these highly glycosylated proteins protect the mucosal barrier while also influencing barrier integrity. Given their indispensable role in maintaining the intestinal mucosal barrier, mucins are compelling candidates for the evaluation of barrier dysfunction. Numerous studies have investigated mucins in the context of IBD, but a clear consensus regarding their expression, polymorphisms, and post-translational modifications is missing. This systematic review summarizes mucin alterations at the transcriptional, translational, and post-translational levels in the presence/absence of intestinal inflammation in IBD patients. Methods: To this end, PubMed, Scopus, and Web of Science were searched for studies published between February 1993 and January 2025, yielding 69 articles eligible for inclusion. Results: The expression of MUC1, MUC5AC, and MUC6 was reported to be upregulated at both RNA (isoform) and protein level, in contrast to MUC12, which exhibited reduced expression in inflamed mucosa only at RNA isoform level. MUC2 was the only mucin consistently downregulated at the protein level, despite unchanged mRNA expression, whereas polymorphisms of MUC2, MUC3A, MUC4, MUC13, MUC19, MUC21, and MUC22 were associated with susceptibility to Crohn’s disease, ulcerative colitis, or IBD in general. Post-translational modifications, such as hypoglycosylation of MUC1 and MUC2, as well as a reduction of mucin sulphation of MUC2 were reported. Conclusion: Together, these findings underscore the involvement of mucins in IBD and point to their potential as biomarkers for barrier dysfunction.