OTUD3 prevents intestinal flora-mediated colitis by regulating STING signaling. Credit score: Hisako Kayama (Sci Immunol. 2025)
Ulcerative colitis (UC) causes distress for thousands and thousands worldwide. It impacts the massive gut, inflicting ache, cramping, and frequent bowel actions with bloody diarrhea. Though some folks undergo intervals after they really feel properly, the illness will immediately flare up, inflicting one other cycle of ache, diarrhea, and weight reduction. There’s at present no treatment.
The intestinal flora performs a significant function in UC, however the actual function is unclear. In wholesome folks, the intestinal flora incorporates all kinds of microbes that assist digestion and supply advantages for the entire physique. In distinction, the intestinal flora of individuals with UC is unbalanced, with fewer useful microbes and extra dangerous microbes. This situation is called dysbiosis.
In a research revealed in Science Immunology, a multi-institutional analysis crew led by the College of Osaka revealed {that a} mixture of dysbiosis, mutations of the OTUD3 gene, and STING signaling worsen UC. These particular mutations of the OTUD3 gene, generally known as single nucleotide variants or SNPs, are thought of as a danger issue for UC.
The important thing to the crew’s discovery lay in learning intestinal flora from wholesome folks and folks with UC.
“We transplanted the intestinal flora of healthy individuals and of patients with UC into mice with mutant OTUD3 and mice with normal OTUD3. The only mice that developed symptoms of UC were the ones with mutant OTUD3 that received UC flora,” says lead creator of the research, Bo Li.
The researchers then seemed for the hyperlink between dysbiosis and the OTUD3 gene mutation. The reply lay in STING, a protein that’s activated by microbes within the intestinal flora when mutated OTUD3 is current.
“We found that dysbiosis in people with UC leads to activation of STING signaling, leading to inflammation in the colon. When we transplanted UC intestinal flora into OTUD3 mutant mice without the STING gene, we saw no symptoms of UC,” explains Li.
The analysis crew’s outcomes present that genes and the intestinal setting work collectively in UC, and that each could also be vital within the seek for new UC therapies.
“We were able to elucidate the mechanism of onset and aggravation of UC, which involves OTUD3 gene mutations and disturbances in the intestinal flora,” says senior creator Hisako Kayama.
“Our study suggests that dysbiosis and STING signaling may be therapeutic targets for UC. We hope our results will lead to improved diagnosis and individualized treatment of UC.”
Extra data:
OTUD3 prevents ulcerative colitis by inhibiting microbiota-mediated STING activation, Science Immunology (2025). DOI: 10.1126/sciimmunol.adm6843
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Osaka College
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Intestinal flora works along with sure genes to worsen ulcerative colitis, analysis reveals (2025, July 18)
retrieved 18 July 2025
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