The part of our nervous system that triggers the ‘fight or flight’ reaction can influence how severe potentially life-threatening C. difficile infections become, as revealed by recent research.
Research from the University of Virginia School of Medicine shows that the segment of our nervous system associated with the “fight or flight” response can significantly affect the severity of potentially lethal C. difficile infections.
The study indicates that physicians might help protect patients from these infections—common issues in hospitals and nursing homes—by administering medications that can calm an overactive nervous system response.
“When we compare what we know about how the immune system impacts C. difficile infections, we barely understand the role of neurons in the disease,” explained William A. Petri Jr., MD, PhD, from UVA Health’s Division of Infectious Diseases and International Health. “By identifying new aspects of the nervous system that exacerbate inflammation, we can pinpoint possible treatment options and markers for patients who are at higher risk of illness.”
About C. Difficile
C. difficile (often referred to as C. diff) presents a continual challenge for healthcare settings. This bacterium naturally resides in our intestines, but extensive use of antibiotics, especially in hospitalized patients or nursing homes, can lead to harmful infections. Each year, around 500,000 people in the U.S. acquire C. difficile infections, with roughly 30,000 fatalities.
Moreover, surviving the intense diarrhea, nausea, fever, and colitis caused by C. difficile doesn’t guarantee safety: According to the federal Centers for Disease Control and Prevention, one in six patients will experience another C. diff infection within eight weeks.
Recent UVA research points to the significant impact of the nervous system on severe C. difficile infections. The study found that the “sympathetic” nervous system, which responds to threats, can actively worsen serious C. diff cases.
Usually, our “fight or flight” response is beneficial for avoiding danger. It allows us to react swiftly, enhances our vision, increases strength, and can also stimulate our immune response to help us heal. However, in cases of C. difficile, the nervous system’s excessive reactions can become problematic, as explained by UVA’s findings.
“Neurons act as the first line of defense against toxic challenges. However, they might not always activate the appropriate response, making the situation worse,” noted David Tyus, a neuroscience graduate student at UVA. “Interestingly, the receptor we identified as significant in C. difficile infection, the alpha 2 adrenergic receptor, has also been associated with irritable bowel syndrome. I’m intrigued to explore potential commonalities between these two conditions.”
Encouragingly, the researchers discovered that targeting the receptor in laboratory mice led to reduced intestinal inflammation and decreased the severity and death rates from C. difficile. This suggests that with further exploration, doctors might adopt similar strategies to treat severe C. diff infections in patients, such as surgically removing parts of the gut’s nerves or developing drugs aimed at the alpha 2 receptor—an effort being pursued by Petri and Tyus.
“Our upcoming research will focus on identifying which cells with the alpha 2 receptor are reacting to signals from the sympathetic nervous system and their involvement in C. difficile-induced illnesses,” Petri shared. “We’re enthusiastic about the potential applications of our findings in clinical practice and how the sympathetic nervous system might contribute to recurrent infections. We hope this study will pave the way for understanding how neurons influence C. difficile infection outcomes.”
Published Findings
The findings were published in the scientific journal Cell Reports Medicine, which is accessible to the public free of charge.
The research team included Tyus, Jhansi L. Leslie, Farha Naz, Jashim Uddin, Brandon Thompson, and Petri. Notably, Petri is also a consultant for TechLab Inc., a firm specializing in diagnostic testing for C. difficile. Additionally, Petri and Tyus are pursuing a patent with UVA for using alpha 2 adrenergic receptor blockade as a treatment for C. difficile colitis.
This study received funding from the National Institutes of Health through grants T32AI007046, F31AI161787-04t, R01348 AI152477, and R01AI124214.
