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Development of Innovative Scoring Systems for Sickness and Tissue Damage From Clostridium difficile Colitis

April 30, 2019
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Researchers from Nationwide Children’s Hospital use a collaborative approach to combat a serious health care threat.

In a new publication, the team reported the development of two novel scoring systems to consistently and efficiently assess sickness and tissue injury during antibiotic-associated C. difficile colitis in a murine model.

“My laboratory at Nationwide Children’s Research Institute has collaborated for several years with two other laboratories, those of Dr. Steven Goodman and Dr. Michael Bailey. Each one has special expertise in different areas: my laboratory has great expertise in animal models of human diseases; the Goodman Laboratory has special expertise in biofilms and probiotics; and the Bailey Laboratory has particular expertise in the microbiome,” says Gail Besner, MD, senior author on the study and chief of Pediatric Surgery at Nationwide Children’s.   

“The sum of what we can accomplish working together is more than just the additive effects of the three laboratories had we been working independently. In the past several years we have discovered that a novel probiotic delivery system, in which we administer the probiotic Lactobacillus reuteri in its biofilm state, can protect the intestines from injury.”

C. difficile colitis can occur when a patient is treated with antibiotics which disrupt the microbiome of the intestinal tract, allowing the pathogenic C. difficile bacteria to flourish. It causes approximately 500,000 infections in patients of all ages, causes over 30,000 deaths, and results in an estimated $4.8 billion for associated health care costs each year in the United States.

After establishing the appropriate doses of antibiotics and C. difficile to create reproducible infection in the model, the team scored signs of sickness using their novel clinical sickness score (CSS; range 0–12); scores ≥6 were consistent with C. difficile colitis.

Intestinal tissue was then analyzed to define a histologic injury score (HIS; range 0-9) to assess tissue damage; scores ≥4 were consistent with C. difficile colitis.

As expected, no control mice showed signs of sickness. Twenty-three percent of mice that received antibiotics alone displayed signs of sickness whereas 65% of mice that received antibiotics and C. difficile had signs of sickness (p = 0.0134). Similarly, no control mice showed histologic injury, whereas 8% of mice that received antibiotics alone and 75% of mice that received antibiotics and C. difficile had histologic injury (p = 0.0001).

“This was the first of the series of papers that will examine the ability of our novel probiotic delivery system to treat Clostridium difficile colitis” says Dr. Besner, who is also a professor at The Ohio State University. “We will soon be publishing a paper, using these grading systems, demonstrating that our novel probiotic delivery system can not only protect the intestines from developing Clostridium difficile colitis, but it can also treat the intestines once a patient, or in our case an animal, is already afflicted by the disease, so we can both prevent and treat the disease with this novel therapy.”

“In the field of probiotics, many people are using bacteria, even in clinical trials, but there is substantial diversity [in methodology] and not enough quality control. We need to be asking if the bacteria that you are using are in the appropriate state. I think medicine and clinical science has moved forward to an appreciation of [how bacteria perform under different conditions]: what state are the bacteria in? What state that you’re going to administer? What states are the bacteria that you already have in your gut? Where are they? What combinations of them do you have?” says Steven Goodman, PhD, principal investigator in the Center for Microbial Pathogenesis at Nationwide Children’s.

“Where we want to go with this is to get it to a level where people will be able to take it as a preventative or a therapeutic, and it will be like any other drug. Like taking an aspirin for a headache.”

 

Citation: 

Shelby RD, Tengberg N, Conces M, Olson JK, Navarro JB, Bailey MT, Goodman SD, Besner GE. Development of a standardized scoring system to assess a murine model of Clostridium difficile colitis. Journal of Investigative Surgery. 2019 Mar 20. [Epub ahead of print]

 

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