LITERATURE UPDATE


remission, and restoration. The document is the result of multidisciplinary input from scientists, clinicians, patients, and funders and represents a valuable resource for patient-centric research prioritisation. This preclinical human IBD mechanisms section identifies major research gaps whose investigation will elucidate pathways and mechanisms that can be targeted to address unmet medical needs in IBD.


Research gaps were identified in the following areas: genetics, risk alleles, and epigenetics; the microbiome; cell states and interactions; barrier function; IBD complications (specifically fibrosis and stricturing); and extraintestinal manifestations. To address these gaps, the authors share specific opportunities for investigation for basic and translational scientists and identify priority actions.


Macrophage polarization in inflammatory bowel disease Zhang K, Guo J, Yan W, Xu L. Cell Commun Signal. 2023 Dec 21;21(1):367. doi: 10.1186/s12964-023-01386-9.


The growing prevalence of inflammatory bowel disease (IBD) has encouraged research efforts, which have contributed to gradual improvements in the understanding of IBD diagnosis and therapeutic approaches. The pathogenesis of IBD has not been fully elucidated, but the combined actions of environmental, genetic, immune factors, and microbial organisms are believed to cause IBD.


In the innate immune system,


macrophages play important roles in maintaining intestinal health and in the development of IBD. Macrophages can be polarised from M0 into several phenotypes, among which M1 and M2 play critical roles in IBD development and the repair of intestinal homeostasis and damage. Certain macrophage-related IBD studies already exist; however, the functions of each phenotype have not been fully elucidated. As technology develops, understanding the link between macrophages and IBD has increased, including the growing knowledge of the developmental origins of intestinal macrophages and their performance of comprehensive functions. This review describes macrophage polarisation in IBD from the perspectives of macrophage development and polarisation, macrophage changes in homeostasis and IBD, metabolic changes, and the mechanisms of macrophage polarisation in IBD. The discussion of these topics provides new insights into immunotherapy strategies for IBD.


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Histology of IBD and related colitides in the elderly


Leoncini G, Reggiani-Bonetti L, Simoncelli G, Villanacci V. Minerva Gastroenterol (Torino). 2024 Mar;70(1):68–78.


doi: 10.23736/S2724-5985.21.02888-6


Inflammatory bowel disease (IBD) is a chronic relapsing condition, affecting both children and adults with a life-long duration. An increased co-morbidity gives raise to fragility in the elderly. In this regard it should consider that several non- IBD colitides may mimic both ulcerative colitis and Crohn’s disease. Moreover, chronic diseases represent a clinical challenge, mostly about treatment effectiveness. It is worth noting that patients with long-standing diseases – and elderly patients among them – have an increased malignancy risk when compared to the general (non-IBD) population. Here, the authors aim to review the


three main histological topics that play a role in the clinical management of IBD in the elderly, namely differential diagnosis, mucosal healing and IBD-associated dysplasia.


Artificial intelligence: A new tool in the pathologist’s armamentarium for the diagnosis of IBD Cannarozzi AL, Massimino L, Latiano A et al. Comput Struct Biotechnol J. 2024 Sep 11;23:3407–17. doi: 10.1016/j.csbj.2024.09.003.


Inflammatory bowel diseases (IBD) are classified into two entities, namely Crohn’s disease (CD) and ulcerative colitis (UC), which differ in disease trajectories, genetics, epidemiological, clinical, endoscopic, and histopathological aspects. As no single golden standard modality for diagnosing IBD exists, the differential diagnosis among UC, CD, and non-IBD involves a multidisciplinary approach, considering professional groups that include gastroenterologists, endoscopists, radiologists, and pathologists. In this context, histological examination of endoscopic or surgical specimens plays a fundamental role. Nevertheless, in differentiating IBD from non-IBD colitis, the histopathological evaluation of the morphological lesions is limited by sampling and subjective human judgment, leading to potential diagnostic discrepancies. To overcome these limitations, artificial intelligence (AI) techniques are emerging to enable automated analysis of medical images with advantages in accuracy, precision, and speed of investigation, increasing interest in the histological analysis of


gastrointestinal inflammation. This review aims to provide an overview of the most recent knowledge and advances in AI methods, summarising its applications in the histopathological analysis of endoscopic biopsies from IBD patients, and discussing its strengths and limitations in daily clinical practice.


Characterisation of IBD heterogeneity using serum proteomics: A multicentre study


Salomon B, Sudhakar P, Bergemalm D et al.; BIO IBD consortium; COLLIBRI consortium; Lindqvist CM, Kruse R, Repsilber D, Verstockt B, Vermeire S, Halfvarson J. J Crohns Colitis. 2024 Nov 4:jjae169.


doi: 10.1093/ecco-jcc/jjae169.


Recent genetic and transcriptomic data highlight the need for improved molecular characterisation of inflammatory bowel disease (IBD). Proteomics may advance the delineation of IBD phenotypes since it accounts for post-transcriptional modifications. Here, the authors aim to assess the IBD spectrum based on inflammatory serum proteins and identify discriminative patterns of underlying biological subtypes across multiple European cohorts. Using proximity extension methodology, the authors measured 86 inflammation-related serum proteins in 1551 IBD patients and 312 healthy controls (HC). They screened for proteins exhibiting significantly different levels among IBD subtypes and between IBD and HC. Classification models for differentiating between Crohn’s disease (CD) and ulcerative colitis (UC) were employed to explore the IBD spectrum based on estimated probability scores. Levels of multiple proteins, such as IL-17A, MMP-10, and FGF-19, differed (fold-change>1.2; FDR<0.05) between ileal vs. colonic IBD. Using multivariable models, a protein signature reflecting the IBD spectrum was identified, positioning colonic CD between UC and ileal CD, which were at opposite ends of the spectrum. Based on area under the curve (AUC) estimates, classification models more accurately differentiated UC from ileal CD (median AUCs>0.73) than colonic CD (median AUCs<0.62). Models differentiating colonic CD from ileal CD demonstrated intermediate performance (median AUCs 0.67–0.69). The authors’ findings in serum proteins support the presence of a continuous IBD spectrum rather than a clear separation of CD and UC. Within the spectrum, disease location may reflect a more similar disease than CD vs. UC, as colonic CD resembled UC more closely than ileal CD.


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