The emerging role of the gut microbiota and its application in inflammatory bowel disease.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a complex disorder with an unknown cause. However, the dysbiosis of the gut microbiome has been found to play a role in IBD etiology, including exacerbated immune responses and defective intestinal barrier integrity. The gut microbiome can also be a potential biomarker for several diseases, including IBD. Currently, conventional treatments targeting pro-inflammatory cytokines and pathways in IBD-associated dysbiosis do not yield effective results. Other therapies that directly target the dysbiotic microbiome for effective outcomes are emerging. We review the role of the gut microbiome in health and IBD and its potential as a diagnostic, prognostic, and therapeutic target for IBD. This review also explores emerging therapeutic advancements that target gut microbiome-associated alterations in IBD, such as nanoparticle or encapsulation delivery, fecal microbiota transplantation, nutritional therapies, microbiome/probiotic engineering, phage therapy, mesenchymal stem cells (MSCs), gut proteins, and herbal formulas.

The Function of Necroptosis and Its Treatment Target in IBD.

Inflammatory bowel disease (IBD), which encompasses Crohn's disease (CD) and ulcerative colitis (UC), is a complicated illness whose exact cause is yet unknown. Necroptosis is associated with IBD pathogenesis, leading to intestinal barrier abnormalities and uncontrolled inflammation. Molecules involved in necroptosis, however, exhibit different expression levels in IBD and its associated colorectal cancer. Multiple studies have shown that inhibiting these molecules alleviates necroptosis-induced IBD. Moreover, due to the severe scarcity of clinical medications for treating IBD caused by necroptosis, we review the various functions of crucial necroptosis molecules in IBD, the stimuli regulating necroptosis, and the current emerging therapeutic strategies for treating IBD-associated necroptosis. Eventually, understanding the pathogenesis of necroptosis in IBD will enable the development of additional therapeutic approaches for the illness.

Effects of DNA methylation and its application in inflammatory bowel disease (Review).

Inflammatory bowel disease (IBD) is marked by persistent inflammation, and its development and progression are linked to environmental, genetic, immune system and gut microbial factors. DNA methylation (DNAm), as one of the protein modifications, is a crucial epigenetic process used by cells to control gene transcription. DNAm is one of the most common areas that has drawn increasing attention recently, with studies revealing that the interleukin (IL)­23/IL­12, wingless­related integration site, IL­6­associated signal transducer and activator of transcription 3, suppressor of cytokine signaling 3 and apoptosis signaling pathways are involved in DNAm and in the pathogenesis of IBD. It has emerged that DNAm­associated genes are involved in perpetuating the persistent inflammation that characterizes a number of diseases, including IBD, providing a novel therapeutic strategy for exploring their treatment. The present review discusses DNAm­associated genes in the pathogenesis of IBD and summarizes their application as possible diagnostic, prognostic and therapeutic biomarkers in IBD. This may provide a reference for the particular form of IBD and its related methylation genes, aiding in clinical decision­making and encouraging therapeutic alternatives.

Exosome-mediated macrophage regulation for inflammatory bowel disease repair: a potential target of gut inflammation.

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a complex condition without a definite cause. During IBD, immune cells such as macrophages release proinflammatory cytokines and chemokines, contributing to intestinal barrier integrity dysfunction. IBD is largely influenced by macrophages, which are classified into subtypes M1 and M2. M1 macrophages have been found to contribute to the development of IBD, whereas M2 macrophages alleviate IBD. Hence, agents that cause increased polarization of the M2 phenotype could help repair IBD. Exosomes, as ubiquitous conveyors of intercellular messages, are involved in immune responses and immune-mediated disease processes. Exosomes and their microRNA (miRNA) from healthy cells have been found to polarize macrophages to M2 to repair IBD due to their anti-inflammatory properties; however, those from inflammatory-driven cells and disease cells promote M1 macrophages to perpetuate IBD. Here, we review the biogenesis, biochemical composition, and sources of exosomes, as well as the roles of exosomes as extracellular vesicles in regulation of macrophages to repair IBD.