The Role of the Gut Microbiota in Colonization Resistance against Clostridium difficile.

gut microbiota;colonization resistance;Clostridium difficile;mathematical modeling;mouse models;Microbiology and Immunology;Science;Microbiology and Immunology

Schubert, AlyxandriaYoung, Vincent Bensan ;

University of Michigan

关键词: gut microbiota;    colonization resistance;    Clostridium difficile;    mathematical modeling;    mouse models;    Microbiology and Immunology;    Science;    Microbiology and Immunology;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/113313/alyx_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

The human body is host to a complex community of microorganisms collectively known as the microbiota. Specifically, the gastrointestinal tract harbors trillions of bacteria with important roles in host health. The gut microbiota can play a critical role in preventing invading microbes from persistently colonizing the gastrointestinal tract, a phenomenon known as colonization resistance. Perturbations, such as antibiotic treatments, which change the structure of the gut microbiota, may in turn alter colonization resistance to pathogenic microbes. Epidemiological studies demonstrate that antibiotic use is a major risk factor for acquiring a Clostridium difficile infection (CDI), which is the leading nosocomial infection in the United States. I hypothesized that multiple bacterial populations contribute to the inhibition of C. difficile colonization. To test this hypothesis, I investigated the role of the gut microbiota in colonization resistance against C. difficile in both humans and mice. Across both hosts, I demonstrated that a loss in Lachnospiraceae, Ruminococcaceae, Porphyromonadaceae, Bacteroides, and Alistipes were highly correlated with loss of colonization resistance. Using mathematical modeling of microbiota abundance data, I showed that the microbiota was a powerful indicator of disease state and could be used to accurately predict levels of C. difficile colonization, effectively measuring the microbiota’s level of resistance against this pathogen. My results demonstrated the importance of the microbiota as a whole in conferring colonization resistance. These studies provide important insight into the relationships between members of the microbiota and C. difficile and further define a consortia of bacteria from which efficient probiotic therapies can be designed.