Clostridium difficile (CD), or C. diff as it is sometimes called, is a common hospital-acquired pathogen that leads to CD infection (CDI), which increases the risk for patient illness and death and raises healthcare costs. CD thrives when a patient's microbial balance—the amount of "good" versus "bad" bacteria—is altered, as happens in response to antibiotics. Patients taking long-term antibiotics are at high-risk of CDI. Currently, the standard-of-care method to prevent CDI is simply to avoid prescribing inappropriate or unnecessary antibiotics.
New Cleveland Clinic research shows there may be a more effective, proactive approach to prevent CDI. The city-wide collaboration, led by Gail A.M. Cresci, PhD, RD, LD, CNSC, Department of Pediatric Gastroenterology, also included researchers from Louis Stokes Cleveland Veterans Affairs Medical Center and Case Western Reserve University.
The study results, published in the Journal of Parenteral and Enteral Nutrition, suggest that supplementing antibiotic therapy with a butyrate-producing probiotic and prebiotic may make the gut environment unfriendly to CD and prevent CDI. Butyrate—which has many anti-inflammatory benefits and is especially important for gut health—is depleted in CDI.
Dr. Cresci and colleagues showed that treating a preclinical model exposed to CD with the commensal bacteria Faecalibacterium prausnitzii and a potato starch prebiotic protected against CDI, as evidenced by low CD concentrations found in stool samples. They found the treatment worked to reduce CD colonization in the gut in several ways.
First, it protected tight junction proteins, which maintain the strength and integrity of intestinal barriers. These proteins typically break down in CDI. They also showed that the treatment reduced the number of specific receptors in the gut available to bind to CD toxins, potentially preventing the toxins from exerting their harmful effects. Lastly, the combination therapy increased the number of immune-supporting cells—including circulating chemokines, neutrophils, monocytes and cytokines—which are necessary for restoring intestinal balance following an infection.
Taken together, these observations show that this specific probiotic and prebiotic, or synbiotic, treatment creates an intestinal environment that is unfavorable for CD. Dr. Cresci says that physicians may consider supplementing antibiotics with a butyrate-supporting probiotic and prebiotic in at-risk patients to prevent CD from colonizing and to mute it's toxic effects. She is hopeful that with further research this targeted prevention strategy may help combat the number of CDI-related deaths that have increased in recent years, due in part to widespread overuse of antibiotics.
Sanjoy Roychowdhury, PhD, is first author on the study which was supported by funds from the National Institute on Alcohol Abuse and Alcoholism, NIH; STERIS Corporation; Cleveland Clinic Children's Hospital; and the National Center for Advancing Translational Sciences, NIH (through a Clinical & Translational Science Award to Case Western Reserve University and Cleveland Clinic). Dr. Cresci holds secondary appointments in the Cleveland Clinic Lerner Research Institute and Digestive Disease & Surgery Institute.