The secret superpower that makes C. difficile so deadly

April 24, 2019

A new discovery about dangerous C. difficile diarrhea has identified a new way that the bacteria—and possibly others like it—cause severe disease. C. diff is the most common hospital-acquired infection and estimated to result in 453,000 cases per year, with 29,300 associated deaths.

The new finding from the School of Medicine explains why certain patients are highly susceptible to C. diff infections, provides doctors with a way to predict disease severity, and points to a new way to treat the often-deadly condition.

The UVA researchers found that the immune response to C. diff causes tissue damage and even death through a type of immune cell called Th17. This solves a longstanding mystery about why disease severity does not correlate with the amount of bacteria in the body but, instead, to the magnitude of the immune response. It also explains why patients with inflammatory bowel disease (IBD) are more likely to suffer severe C. diff infections and more likely to die from them.

The bowel condition colitis, the researchers determined, has a lingering effect on the immune system, priming the patient for a worse C. diff infection. While scientists have known that C. diff and other bacteria produce toxins that are harmful to the body, they assumed this was a simple matter: more toxin, more sickness. But UVA’s research reveals that the truth is far more complex. Oftentimes, the type of immune response generated by the body can dictate the outcome of disease independently of bacterial toxin.

The bowel condition colitis has a lingering effect on the immune system, priming the patient for a worse C. diff infection. While scientists have known that C. diff and other bacteria produce toxins that are harmful to the body, they assumed this was a simple matter: more toxin, more sickness. But UVA’s research reveals that the truth is far more complex. Oftentimes, the type of immune response generated by the body can dictate the outcome of disease independently of bacterial toxin.

Seeking to understand why patients with IBD are so susceptible to C. diff, researcher Mahmoud Saleh created a mouse model of colitis, one of the common forms of IBD. He was able to determine that mice that recovered from colitis actually had changes in their immune system—an adaptive immune response. Immune cells known as Th17 cells had become hypercharged, primed to cause a severe reaction to subsequent C. difficile infection. Even the same amount of the bacteria would now cause a dangerous, outsized response.

The researchers then looked at human samples to determine if their finding would hold true. It did, and they were able to use substances in the blood, including a protein known as interleukin 6 (IL-6), to predict disease severity. Patients with high amounts of IL-6 were almost eight times more likely to die from C. difficile than those with low levels.

UVA has the full article        

Photo 55901642 © Monkey Business Images | Dreamstime.com
Photo 5763532 © Gilles Decruyenaere | Dreamstime.com
Photo 60947671 © Jarun011 | Dreamstime.com
Photo 86264954 © salinrat prasatkaew | Dreamstime.com
Photo 320485969 © Klarion7 | Dreamstime.com