Targeting bad bacteria and the immune system in isolation may help fight deadly infections

Twenty to 50 per cent of all critically ill patients contract potentially deadly infections during their stay in the intensive care unit or in hospital after being in the ICU – markedly increasing the risk of death.

Despite the use of antibiotics, hospital-acquired infections are a major clinical problem that persists to be a huge issue for which we don't have good solutions. We tackled this issue from a different angle. We looked at the body's natural defense to infection to better understand why some people are more susceptible to these deadly infections."

Dr. Braedon McDonald, MD, PhD, an intensive care physician at the Foothills Medical Centre (FMC) and assistant professor at the Cumming School of Medicine (CSM)

The study involved 51 patients newly admitted to the intensive care unit (ICU) at FMC. Patients were studied over the first week of acute critical illness. The research showed that the gut microbiota and systemic immunity work together as a dynamic "metasystem," in which problems with gut microbes and immune system dysfunction are associated with significantly increased rates of hospital-acquired infections.

"The signal that we've seen in our research is that a family of bacteria, that naturally live in the gut, seems to be important for directing the immune system," says Jared Schlechte, PhD candidate in McDonald's lab and first author of the study. "However, during critical illness the microbiome becomes injured allowing these bacteria to start taking over."

The study published in Nature Medicine found that patients who experienced an abnormal increase in the growth of this common bacteria, called a bloom, were at the highest risk of severe infections.

"This information is important because it gives us a whole new avenue to start thinking about not just ways to treat infections, but a potential treatment to prevent them," says McDonald. "The findings suggest that if we want to fight infection, we can't just target these bad bacteria in isolation and the immune system in isolation. We really need to have a more holistic view of how things are functioning." McDonald says the study's findings

As a next step, McDonald and the team plan to launch a randomized, controlled clinical trial – based on a precision medicine approach that borrows from probiotics therapy, and utilizes multiple different bacteria engineered to specifically target the bacteria identified in the study. People who agree to participate will be given engineered microbiomes.

"What we're trying to do is restore the normal mechanism that work when we're healthy, and take advantage of that to help protect people from infections," McDonald says.

UCalgary faculty co-authors included Drs. Christopher Doig, MD, Kathy McCoy, PhD, and Mary Dunbar, MD. PhD candidate Amanda Zucoloto, along with research technician and laboratory manager Ian-Ling Yu, also co-authored the study. The study was supported by the Canadian Institutes of Health Research and the Alberta Health Services Critical Care Strategic Clinical Network.