期刊
MOLECULAR SYSTEMS BIOLOGY
卷 17, 期 10, 页码 -出版社
WILEY
DOI: 10.15252/msb.202110355
关键词
Clostridioides difficile; computational modeling; ecological interactions; pathogen invasion; systems biology
资金
- National Institutes of Health [R35GM124774]
- National Institute of Biomedical Imaging and Bioengineering [R01EB030340]
- Army Research Office [W911NF1910269]
- National Institute of General Medical Sciences of the National Institutes of Health [T32GM008349]
- National Human Genome Research Institute [T32HG002760]
- U.S. Department of Defense (DOD) [W911NF1910269] Funding Source: U.S. Department of Defense (DOD)
This study explores the principles of gut microbiome colonization resistance to the pathogen Clostridioides difficile, demonstrating a strong negative interaction between C. difficile and other species, inhibition mechanisms such as environment acidification and resource competition were identified. Increasing the initial density of C. difficile can increase its abundance in the community, but the maximum achievable abundance is determined by the community context.
Understanding the principles of colonization resistance of the gut microbiome to the pathogen Clostridioides difficile will enable the design of defined bacterial therapeutics. We investigate the ecological principles of community resistance to C. difficile using a synthetic human gut microbiome. Using a dynamic computational model, we demonstrate that C. difficile receives the largest number and magnitude of incoming negative interactions. Our results show that C. difficile is in a unique class of species that display a strong negative dependence between growth and species richness. We identify molecular mechanisms of inhibition including acidification of the environment and competition over resources. We demonstrate that Clostridium hiranonis strongly inhibits C. difficile partially via resource competition. Increasing the initial density of C. difficile can increase its abundance in the assembled community, but community context determines the maximum achievable C. difficile abundance. Our work suggests that the C. difficile inhibitory potential of defined bacterial therapeutics can be optimized by designing communities featuring a combination of mechanisms including species richness, environment acidification, and resource competition.
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