2015 WWMB Project

Modeling the Effects of Antimicrobial Therapy on Gut Microbiota and Clostridium difficile

Project Leaders:
Suzanne Lenhart, Mathematics, Univ. of Tennessee, Knoxville
Cristina Lanzas, Infectious Disease, North Carolina State Univ., Raleigh

Background
Clostridium difficile is an anaerobic human pathogen that forms spores, produce toxins and resides in the gut. Clostridium difficile infection (CDI) is an important hospital acquired infection that causes diarrhea, pseudomembranous colitis, and possibly death. In the last decade, the incidence and severity of C. difficile infection has increased at alarming rates throughout North America, especially in the elderly. In the latest report on antibiotic resistance threats in the United States released by the Centers for Disease Control in 2013, C. difficile was classified within the highest threat level of urgent.

Antimicrobial therapy is often a strong and independent risk factor for CDI because it disrupts the indigenous microbiota, which provides protection against C. difficile colonization. The gut microbiota provides protection against C. difficile colonization through both direct and indirect mechanisms. Direct mechanisms include competing for nutrients or producing bacteriocins that suppress C. difficile. Indirect mechanisms include interactions between gut microbiota and host that trigger immune responses against C. difficile.

Objective

We will develop and analyze mathematical models that account for the interactions between gut microbiota and C. difficile and the perturbation that antimicrobial therapy causes on the gut microbiota to investigate the following questions:

• What is the relative importance of the mechanisms by which the gut microbiota inhibits C. difficile?
• What is the potential effect of antimicrobial therapy on the gut colonization resistance against C. difficile?
• What is the resilience of the different inhibitory mechanisms against antimicrobial therapy perturbations?

References

1. Britton, R.A., Young, V.B., 2012. Interaction between the intestinal microbiota and host in Clostridium difficile colonization resistance. Trends in Microbiology 20, 313-319.
2. Bucci, V., Xavier, J.B., 2014. Towards Predictive Models of the Human Gut Microbiome. Journal of Molecular Biology In press DOI: 10.1016/j.jmb.2014.03.017.

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From 2008 until early 2021, NIMBioS was supported by the National Science Foundation through NSF Award #DBI-1300426, with additional support from The University of Tennessee, Knoxville. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.