In a new study published today in Nature Communications, researchers at the University of Ottawa’s Faculty of Medicine and the Children’s Hospital of Eastern Ontario (CHEO), along with international collaborators, reveal new insights into treating Crohn’s disease (CD), which affects a growing number of children in Canada.
Crohn’s disease is a chronic inflammatory bowel disease that commonly affects children and adolescents, with approximately 20%–30% of all patients presenting the first symptoms when they are under the age of 20. Along with common symptoms such as diarrhea, rectal bleeding and severe abdominal pain, children with CD can experience growth failure, malnutrition and puberty delays. The exact cause of CD is unknown, and doctors have yet to find a cure.
The disease is characterized by chronic irritation or inflammation of the intestinal tract lining, and current treatment involves drugs that work to neutralize an immune system protein known as tumor necrosis factor (TNF).
To find a new way of treating the often debilitating disease, a team of researchers led by Alain Stintzi, professor at uOttawa’s Department of Biochemistry, Microbiology and Immunology; David Mack, professor at the Department of Pediatrics and Director of CHEO’s Inflammatory Bowel Disease Centre; Daniel Figeys, professor at uOttawa’s Department of Biochemistry, Microbiology and Immunology; and Christian Jobin, professor at the Department of Medicine of the University of Florida, have turned their attention to the dynamics of gut bacteria.
“Most current medications for Crohn’s disease are directed towards altering the immune system of the patient, but our current line of investigations suggests that perhaps a different approach may be taken, one that alters the harmful metabolic activities of the bacterial networks in the intestinal tract to treat the inflammation caused by Crohn’s disease,” says Dr. Mack.
The team found that patients suffering from CD presented a significantly lower prevalence of protective microorganisms which produce butyrate, an anti-inflammatory fatty acid, such as bacteria in the Clostridium XIVa and IV groups, and higher rates of harmful bacteria known to produce pro-inflammatory agents, notably hydrogen sulfide, or H2S. Importantly, their findings also showed that CD patients experienced a concurrent decrease in their ability to detoxify and reduce levels of H2S in their intestinal tract lining.
The team showed that bacteria from the strain Atopobium parvulum, a potent H2S producer, induces severe colitis and that the development of colitis caused by that bacteria also requires the presence of the gut microbiota (the microbe population living in the intestinal tract). Taken together, these findings point to a new mechanism in Crohn’s disease, in which the balance between the production and the detoxification of H2S is altered. This opens the door for new treatments aimed at restoring a healthy balance in gut microbiota.