Patients with inflammatory bowel disease (IBD) have higher levels of inflammatory mitochondrial DNA (mtDNA) in the blood, which correlate with disease flare-ups and severity, a study reports.
Researchers say these findings could lead to new treatments for IBD, which currently has no cure.
The study, “Mitochondrial DNA Is a Pro-Inflammatory Damage-Associated Molecular Pattern Released During Active IBD,” appeared in the journal Inflammatory Bowel Diseases.
Mitochondria, which are responsible for the production of energy in cells, descend from an ancient type of bacteria. The mtDNA molecule shares significant similarities with modern bacteria, and is known for its role in several inflammatory diseases.
In IBD patients, mtDNA is not properly recycled and disposed of after mitochondrial damage like it is in healthy people. Instead, it can leak from the gut into the bloodstream and cause inflammation.
Scientists at the University of Edinburgh evaluated whether mtDNA is released from cells during IBD flare-ups. Between 2014 and 2015, they collected blood samples from 97 IBD patients — 67 with ulcerative colitis (UC) and 30 with Crohn’s disease (CS) — as well as 40 healthy people used as controls.
The investigators measured circulating mtDNA levels in patients and in a mouse model of colitis. They also assessed mitochondrial damage and levels of the protein TLR9, a link between mtDNA and inflammation, in the guts of IBD patients.
Results showed that mtDNA levels in the blood were higher in patients with UC and CD than in controls. The levels correlated with those of blood — including numbers of white cells — and clinical markers of disease activity and severity. In fact, patients with the most severe IBD had the highest levels of mtDNA.
Data also revealed mitochondrial damage in the guts of UC patients, as well as higher fecal mtDNA levels and increased production of TLR9.
Similar findings were observed in mice, where blood mtDNA levels were increased during induction of acute colitis and were associated with more severe disease.
Besides a significant contribution to understanding the causes of IBD, the scientists believe mtDNA could be a marker of disease progression and enable effective and personalized treatments.
“We present the first evidence to show that mtDNA is released during active IBD,” the researchers wrote. The findings “point to mtDNA-TLR9 as a therapeutic target in IBD,” they said.
“We are now investigating how to block these molecules from triggering inflammation, in the hope of developing new therapies to prevent disease flare-ups and to accelerate patient recovery after an attack,” Gwo-Tzer Ho, MD, PhD, the study’s senior author, said in a press release.