Mounting evidence underscores the pivotal role of the intestinal barrier and its convoluted network with diet and intestinal microbiome in the pathogenesis of inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CRC). Moreover, the bidirectional association of the intestinal barrier with the liver and brain, known as the gut-brain axis, plays a crucial role in developing complications, including extraintestinal manifestations of IBD and CRC metastasis. Consequently, barrier healing represents a crucial therapeutic target in these inflammatory-dependent disorders, with barrier assessment predicting disease outcomes, response to therapy and extraintestinal manifestations. New advanced technologies are revolutionising our understanding of the barrier paradigm, enabling the accurate assessment of the intestinal barrier and aiding in unravelling the complexity of the gut-brain axis. Cutting-edge endoscopic imaging techniques, such as ultra-high magnification endocytoscopy and probe-based confocal laser endomicroscopy, are new technologies allowing real-time exploration of the cellular intestinal barrier. Additionally, novel advanced spatial imaging technology platforms, including multispectral imaging, upconversion nanoparticles, digital spatial profiling, optical spectroscopy and mass cytometry, enable a deep and comprehensive assessment of the molecular and ultrastructural barrier. In this promising landscape, artificial intelligence plays a pivotal role in standardising and integrating these novel tools, thereby contributing to barrier assessment and prediction of outcomes. Looking ahead, this integrated and comprehensive approach holds the promise of uncovering new therapeutic targets, breaking the therapeutic ceiling in IBD. Novel molecules, dietary interventions and microbiome modulation strategies aim to restore, reinforce, or modulate the gut-brain axis. These advancements have the potential for transformative and personalised approaches to managing IBD.
Intestinal fibrosis is one of the most threatening complications of Crohn’s disease. It occurs in more than a third of patients with this condition, is associated with increased morbidity and mortality, and surgery often represents the only available therapeutic option. The mechanisms underlying intestinal fibrosis are partly known. Studies conducted so far have shown a relevant pathogenetic role played by mesenchymal cells (especially myofibroblasts), cytokines (e.g., transforming growth factor-β), growth factors, microRNAs, intestinal microbiome, matrix stiffness, and mesenteric adipocytes. Further studies are still necessary to elucidate all the mechanisms involved in intestinal fibrosis, so that targeted therapies can be developed. Although several pre-clinical studies have been conducted so far, no anti-fibrotic therapy is yet available to prevent or reverse intestinal fibrosis. The aim of this review is to provide an overview of the main therapeutic targets currently identified and the most promising anti-fibrotic therapies, which may be available in the near future.
15 May 2024 in The Lancet Gastroenterology & Hepatology
Integrating artificial intelligence into inflammatory bowel disease (IBD) has the potential to revolutionise clinical practice and research. Artificial intelligence harnesses advanced algorithms to deliver accurate assessments of IBD endoscopy and histology, offering precise evaluations of disease activity, standardised scoring, and outcome prediction. Furthermore, artificial intelligence offers the potential for a holistic endo-histo-omics approach by interlacing and harmonising endoscopy, histology, and omics data towards precision medicine. The emerging applications of artificial intelligence could pave the way for personalised medicine in IBD, offering patient stratification for the most beneficial therapy with minimal risk. Although artificial intelligence holds promise, challenges remain, including data quality, standardisation, reproducibility, scarcity of randomised controlled trials, clinical implementation, ethical concerns, legal liability, and regulatory issues. The development of standardised guidelines and interdisciplinary collaboration, including policy makers and regulatory agencies, is crucial for addressing these challenges and advancing artificial intelligence in IBD clinical practice and trials.
Patients affected by inflammatory bowel disease (IBD) have a two-fold higher risk of developing colorectal cancer (CRC) than the general population. IBD-related CRC follows a different genetic and molecular pathogenic pathway than sporadic CRC and can be considered a complication of chronic intestinal inflammation. Since inflammation is recognised as an independent risk factor for neoplastic progression, clinicians strive to modulate and control disease, often using potent therapy agents to achieve mucosal healing and decrease the risk of colorectal cancer in IBD patients. Improved therapeutic control of inflammation, combined with endoscopic advances and early detection of pre-cancerous lesions through surveillance programs, explains the lower incidence rate of IBD-related CRC. In addition, current research is increasingly focused on translating emerging and advanced knowledge in microbiome and metagenomics into personalised, early, and non-invasive CRC screening tools that guide organ-sparing therapy in IBD patients. This review aims to summarise the existing literature on IBD-associated CRC, focusing on new insights into the alteration of the intestinal barrier and the interactions with the gut microbiome as the initial promoter. In addition, the role of OMIC techniques for precision medicine and the impact of the available IBD therapeutic armamentarium on the evolution to CRC will be discussed.
Little is known regarding coronavirus disease 2019 (COVID-19) clinical spectrum in non-Asian populations. We herein describe the impact of COVID-19 on liver function in 100 COVID-19 consecutive patients (median age 70 years, range 25–97; 79 males) who were admitted to our internal medicine unit in March 2020. We retrospectively assessed liver function tests, taking into account demographic characteristics and clinical outcome. A patient was considered as having liver injury when alanine aminotransferase (ALT) was > 50 mU/ml, gamma-glutamyl transpeptidase (GGT) > 50 mU/ml, or total bilirubin > 1.1 mg/dl. Spearman correlation coefficient for laboratory data and bivariable analysis for mortality and/or need for intensive care were assessed. A minority of patients (18.6%) were obese, and most patients were non- or moderate-drinkers (88.5%). Liver function tests were altered in 62.4% of patients, and improved during follow-up. None of the seven patients with known chronic liver disease had liver decompensation. Only one patient developed acute liver failure. In patients with altered liver function tests, PaO2/FiO2 < 200 was associated with greater mortality and need for intensive care (HR 2.34, 95% CI 1.07–5.11,p = 0.033). To conclude, a high prevalence of altered liver function tests was noticed in Italian patients with COVID-19, and this was associated with worse outcomes when developing severe acute respiratory distress syndrome.
Several advanced imaging techniques are now available for endoscopists managing inflammatory bowel disease (IBD) patients. These tools, including dye‐based and virtual chromoendoscopy, probe‐based confocal laser endomicroscopy and endocytoscopy, are increasingly innovative applications in clinical practice. They allow for a more in‐depth and refined evaluation of the mucosal and vascular bowel surface, getting closer to histology. They have demonstrated a remarkable ability in assessing intestinal inflammation, histologic remission, and predicting relapse and favorable long‐term outcomes. In addition, the future application of molecular endoscopy to predict biological drug responses has yielded preliminary but encouraging results. Furthermore, these techniques are crucial in detecting and characterizing IBD‐related dysplasia, assisting endoscopic mucosal resection and submucosal dissection towards a surgery‐sparing approach. Artificial intelligence (AI) holds great potential in this promising landscape, as it can provide an objective and reproducible assessment of inflammation and dysplasia. Moreover, it can improve the prediction of outcomes and aid in subsequent therapeutic decision‐making. This review aims to summarize the promising role of state‐of‐the‐art advanced endoscopic techniques and related AI‐enabled models for managing IBD, paving the way for precision medicine.
About Me
Resident in Internal Medicine at IRCCS Policlinico San Matteo, Pavia
Resident in Internal Medicine at IRCCS Policlinico San Matteo, Pavia