Ulcerative colitis (UC) affects millions worldwide, causing pain, cramping, and frequent bowel movements with bloody diarrhea. While some patients experience periods of wellness, flare-ups can suddenly occur, bringing renewed cycles of discomfort, diarrhea, and weight loss. There is currently no cure for this condition.
The role of the gut microbiome in UC remains unclear. In healthy individuals, diverse microbes aid digestion and benefit overall health. However, those with UC have dysbiosis, characterized by fewer beneficial and more harmful microbes.
A recent study published in Science Immunology, led by Osaka University, revealed that a combination of dysbiosis, OTUD3 gene mutations, and STING signaling exacerbates UC. Specific OTUD3 SNPs are considered risk factors for the disease.
Science Immunology:The research team discovered this link by studying the intestinal flora from healthy individuals and those with UC.
"We transplanted both healthy and UC-intestinal flora into mice, some with mutant OTUD3 genes and others with normal genomes. Only the mice with mutated OTUD3 that received UC flora developed symptoms," said lead author Bo Li.
The researchers then found a connection between dysbiosis and OTUD3 mutations via STING protein activation by intestinal microbes when mutated OTUD3 is present.
"We determined that dysbiosis in people with UC activates STING signaling, leading to colon inflammation. When we transplanted UC flora into OTUD3 mutant mice without the STING gene, no symptoms of UC appeared," Li explained.
The team's findings indicate that genes and intestinal environment work together in UC development. Understanding this interaction could be crucial for finding new treatments.
"We've uncovered the mechanism by which OTUD3 mutations and gut flora disturbances contribute to UC onset and worsening," said senior author Hisako Kayama.
This study suggests potential therapeutic targets, aiming to improve diagnosis and individual treatment strategies for UC.