Autophagy refers to the process involving the decomposition of intracellular components via lysosomes. Autophagy plays an important role in maintaining and regulating cell homeostasis by degrading intracellular components and providing degradation products to cells. In vivo, autophagy has been shown to be involved in the starvation response, intracellular quality control, early development, and cell differentiation. Recent studies have revealed that autophagy dysfunction is implicated in neurodegenerative diseases and tumorigenesis. In addition to the discovery of certain disease-causing autophagy-related mutations and elucidation of the pathogenesis of conditions resulting from the abnormal degradation of selective autophagy substrates, the activation of autophagy is essential for prolonging life and suppressing aging. This article provides a comprehensive review of the role of autophagy in health, physiological function, and autophagy-related disease.

Patients with chronic inflammatory bowel diseases are at an increased risk of developing colitis-associated cancer (CAC). Chronic inflammation positively correlates with tumorigenesis. Similarly, the cumulative rate of incidence of developing CAC increases with prolonged colon inflammation. Immune signaling pathways, such as nuclear factor (NF)-κB, prostaglandin E2 (PGE2)/cyclooxygenase-2 (COX-2), interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3), and IL-23/T helper 17 cell (Th17), have been shown to promote CAC tumorigenesis. In addition, gut microbiota contributes to the development and progression of CAC. This review summarizes the signaling pathways involved in the pathogenesis following colon inflammation to understand the underlying molecular mechanisms in CAC tumorigenesis.

Cytokine-targeted therapies have shown efficacy in treating patients with ulcerative colitis (UC), but responses to these advanced therapies can vary. This variability may be due to differences in cytokine profiles among patients with UC. While the etiology of UC is not fully understood, abnormalities of the cytokine profiles are deeply involved in its pathophysiology. Therefore, an approach focused on the cytokine profile of individual patients with UC is ideal. Recent studies have demonstrated that molecular analysis of cytokine profiles in UC can predict response to each advanced therapy. This narrative review summarizes the molecules involved in the efficacy of various advanced therapies for UC. Understanding these associations may be helpful in selecting optimal therapeutic agents.

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus (the human herpesvirus 5) and an opportunistic pathogen that primarily infects HIV-positive and other immuno-compromised patients. Retrospective studies in the field of inflammatory bowel disease (IBD) have suggested a relationship between a concomitant colonic HCMV infection and poor outcomes in patients with an ulcerative colitis (UC) due to the presence of HCMV in surgical specimens of patients with a toxic megacolon or a steroid-resistant UC. Therefore, gastroenterologists have focused on the contribution of HCMV infections in the exacerbation of UC. Numerous studies have addressed the benefits of treating colonic HCMV reactivation in UC using an antiviral treatment. However, its clinical relevance remains uncertain as only a few prospective studies have assessed the direct relationship between clinical outcomes and the viral load of HCMV in colonic tissues. HCMV reactivation can be triggered by inflammation according to fundamental research studies. Thus, optimal control of intestinal inflammation is essential for preventing an HCMV reactivation in the intestinal mucosa. Indeed, several reports have indicated the effectiveness of an anti-tumor necrosis factor-alpha (TNFα) treatment in patients with an active UC and concomitant HCMV infections. In this review, we describe the mechanism of HCMV reactivation in UC cases and discuss the current issues regarding diagnosis and treatment of HCMV infections in UC patients.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by the infiltration IgG4-positive plasma cells and fi brosis in organs throughout the body. IgG4-RD involvement in the gastrointestinal (GI) tract (IgG4-related GI disease; IgG4-GID) is rare, and the disease concept remains unclear. Generally, IgG4-GID has been reported with morphological changes, including ulcers, strictures, and submucosal tumors. Here, we report case of IgG4-GID with persistent diarrhea and abdominal pain in which typical endoscopic fi ndings were absent. This case suggests the unidentified clinical features of IgG4-GID.

Inflammatory bowel disease (IBD) is characterized by intestinal barrier disruption and dysregulated interactions between host immunity and gut microbiota. Osteopontin (OPN) is considered a proinflammatory mediator in IBD, but nonhematopoietic cell-derived OPN may exert barrier-protective functions. This study aimed to determine the effects of OPN in a murine model of acute colitis. We examined wild-type and OPN knockout mice under steady-state conditions and in dextran sulfate sodium–induced colitis, including bone marrow chimeras to distinguish the effects of hematopoietic and nonhematopoietic OPN. Overt colitis did not occur under steady-state conditions. Compared with wild-type mice, OPN knockout mice exhibited crypt elongation, goblet cell hyperplasia, and increased epithelial proliferation. Gene expression analysis revealed reduced interleukin (IL)-22, IL-23, and IL-13 levels alongside increased interferon-γ, IL-1β, and IL-17A levels. 16S rRNA sequencing revealed increased alpha diversity, expansion of Akkermansia and Prevotellaceae, and reduced Lactobacillus abundance. Functional prediction identified enrichment of microbial sulfur metabolism pathways, and metabolomic analysis demonstrated increased L-proline and L-(−)-fucose levels and reduced β-sitosterol levels. These shifts indicate enhanced mucinolytic activity and altered energy metabolism, consistent with a latent “preinflammatory state.” Bone marrow chimera experiments demonstrated that OPN deficiency in the recipients reproduced changes in the microbiota composition and lipocalin-2 expression at the steady state and conferred heightened susceptibility to dextran sulfate sodium–induced acute colitis, irrespective of donor genotype. These findings indicate that nonhematopoietic cell-derived “guardian-type” OPN preserves barrier integrity, sustains IL-22/IL-23 production, and maintains microbiota–metabolome balance, whereas its loss induces a preinflammatory state that predisposes to acute mucosal injury. These findings provide a conceptual basis for stage- and source-specific therapeutic strategies in IBD.