Open AccessNegative interactions determine Clostridioides difficile growth in synthetic human gut communities
Author(s) -
Hromada Susan,
Qian Yili,
Jacobson Tyler B,
Clark Ryan L,
Watson Lauren,
Safdar Nasia,
AmadorNoguez Daniel,
Venturelli Ophelia S
Publication year - 2021
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.202110355
Subject(s) - biology , clostridioides , competition (biology) , microbiome , context (archaeology) , species richness , abundance (ecology) , clostridium difficile , resistance (ecology) , colonization , ecology , microbiology and biotechnology , bioinformatics , antibiotics , paleontology
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.