Inflammatory bowel diseases (IBD), represented by Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, relapsing, systemic, and immune-mediated inflammatory diseases that cause gastrointestinal damage. Although the exact pathogenesis remains unknown, our understanding of the pathophysiology of and genetic predisposition to IBD has dramatically improved with investigations using animal models and genome-wide association studies. More recently, research has been vigorously underway using integrated experimental methods such as organoid-based models or single-cell analysis. The gut microbiota has also become a major interest because the commensal microbiota plays a pivotal role in maintaining homeostasis of the intestinal microenvironment and reflects the interaction of host genetics with dynamic exposure to the innumerable stimuli from the exposome [1].

This improved understanding of the disease pathophysiology of IBD, especially the role of cytokines in the inflammatory cascade, has expanded the therapeutic armamentarium for IBD. This trend was propelled by the enormous success of anti-tumor necrosis factor-α antagonists, which was followed by the discovery that long-term maintenance with biologics can improve the natural history of IBD [2, 3]. As a result, upward modification of therapeutic targets became conceivable, and the STRIDE-II position statement established sequential targets in the management of IBD [4]. At present, mucosal healing is considered a reasonable long-term target in the treatment of IBD; however, the definition of mucosal healing in UC is controversial, and endoscopic evaluation of the small bowel in patients with CD is not taken into account. In this sense, identification of appropriate biomarkers is crucial for implementation of the “treat-to-target” approach in real-world IBD management. The validity of histological healing in UC and transmural healing in CD as long-term targets remains debatable.

In contrast to the striking therapeutic efficacy of biologics and small-molecular drugs, these medications also cause some problems, especially with respect to cost and safety. Thus, the de-escalation or withdrawal of these medications in patients with remitters has recently been discussed [5]. Continuous investigation is necessary to elucidate the long-term safety of these medications. Other than biologics and small-molecular drugs, two main unresolved issues remain in the management of IBD. The first issue is the increasing prevalence of intolerance to 5-aminosalicylic acid (5-ASA). Although conventional, 5-ASA is an essential medication for IBD. Furthermore, some retrospective studies have demonstrated a possible increased risk of colectomy among patients who are intolerant of 5-ASA [6]. Thus, therapeutic strategies for such patients should be rigorously discussed. The second issue is the surveillance and management of UC-associated neoplasia. Recent advances in endoscopic equipment and diagnostic techniques have improved the detection of UC-associated neoplasia in the early stage. The SCENIC consensus statement has been referred to for the possible application of therapeutic endoscopy to these lesions [7]; however, the issue remains controversial.

This special issue of Digestion focuses on recent topics in the field of IBD from both basic and clinical perspectives. Upcoming therapeutic targets are also addressed. We believe that this comprehensive review by IBD specialists provides indispensable knowledge and indicates future directions for better understanding and management of IBD.

The authors have no conflicts of interest to declare with regards to the manuscript.

The authors received no funding for this editorial.

Motohiro Esaki drafted and provided final approval of the article. Masayuki Saruta was responsible for the critical revision and final approval of the article.

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