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Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions of the gastrointestinal tract that are multifactorial in nature. The pathophysiology involves interactions between the host immune system and environmental factors, including the gut microbiota, in genetically predisposed individuals. Advances in understanding these interactions have led to the development of novel therapeutic targets, ranging from anti-TNFα to more recent anti-interleukin 23 treatments. However, some patients still experience resistance to these therapies. Monogenic intestinal diseases (MIDs), which present with more severe symptoms than IBD and typically begin early in life, result from significant disruptions of intestinal homeostasis. MIDs are driven by mutations in a single gene, offering a unique opportunity to explore the mechanisms underlying intestinal homeostasis in health. In this review, we provide a comprehensive overview of the mechanisms of intestinal homeostasis by examining the cellular and molecular features of IBD and MID pathophysiologies.
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http://dx.doi.org/10.3390/ijms26136133 | DOI Listing |
Front Pharmacol
August 2025
Microbiota Lab, Department of Pharmaceutical Microbiology and Bioanalysis, Medical University of Warsaw, Warsaw, Poland.
Gastrointestinal eubiosis is essential for maintaining overall host wellbeing. Post-weaning diarrhea (PWD) is a common issue in pig development, arising from weaning stress, which disrupts the gut microbiota balance and increases susceptibility to infections. The primary bacterial pathogen linked to PWD is enterotoxigenic (ETEC).
View Article and Find Full Text PDFCell Mol Immunol
September 2025
Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China.
Anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD) is hampered by issues of nonresponse and resistance, highlighting the urgent need for alternative or complementary treatments. Our study revealed significant upregulation of taurine in the intestinal tissues of IBD patients, which was inversely related to the severity of the disease. A key discovery was that TNF directly induced taurine synthesis in intestinal epithelial cells and increased the production of angiogenin, a nuclease that degrades mitochondrial RNA, which is known to amplify inflammatory responses.
View Article and Find Full Text PDFBlood
September 2025
Université Paris cité, INSERM, Institut Cochin, CNRS, Paris, France.
Hepcidin is the key hyposideremic hormone produced primarily by the liver. However, recent reports reveal extra-hepatic functional sources of hepcidin, including the intestine, the site of dietary iron absorption. To determine whether intestinal hepcidin may play a role in plasma iron lowering, we generated transgenic mice overexpressing the peptide specifically in this tissue.
View Article and Find Full Text PDFElife
September 2025
Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Sickness-induced sleep is a behavior conserved across species that promotes recovery from illness, yet the underlying mechanisms are poorly understood. Here, we show that interleukin-6-like cytokine signaling from the gut to brain glial cells regulates sleep. Under healthy conditions, this pathway promotes wakefulness.
View Article and Find Full Text PDFJ Exp Med
November 2025
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Host-pathogen interactions involve two critical strategies: resistance, whereby hosts clear invading microbes, and tolerance, whereby hosts carry high pathogen burden asymptomatically. Here, we investigate mechanisms by which Salmonella-superspreader (SSP) hosts maintain an asymptomatic state during chronic infection. We found that regulatory T cells (Tregs) are essential for this disease-tolerant state, limiting intestinal immunopathology and enabling SSP hosts to thrive, while facilitating Salmonella transmission.
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