Negative interactions determine Clostridioides difficile growth in synthetic human gut communities
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. Us...
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Published in | Molecular systems biology Vol. 17; no. 10; pp. e10355 - n/a |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
EMBO Press
01.10.2021
John Wiley and Sons Inc Springer Nature |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
SYNOPSIS
A combination of bottom‐up community assembly and computational modeling reveals determinants of Clostridioides difficile growth in synthetic human gut communities.
The inferred interspecies interaction network reveals that C. difficile receives the largest number and magnitude of incoming negative interactions.
The richness of a community, environmental acidification by a community, propagule pressure and resource competition are major determinants of C. difficile growth.
Clostridium hiranonis consumes resources utilized by C. difficile and inhibits C. difficile growth.
A combination of bottom‐up community assembly and computational modeling reveals determinants of Clostridioides difficile growth in synthetic human gut communities. |
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ISSN: | 1744-4292 1744-4292 |
DOI: | 10.15252/msb.202110355 |