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Understanding the principles of colonization resistance of the gut microbiome to the pathogen Clostridioides difficile will enable the design of next generation defined bacterial therapeutics. We investigate the ecological principles of community resistance to C. difficile invasion using a diverse synthetic human gut microbiome. Our results show that species richness is a key determinant of C. difficile growth across a wide range of ecological contexts. Using a dynamic computational model, we demonstrate that C. difficile receives the largest number and magnitude of incoming negative interactions. We identify molecular mechanisms of inhibition including acidification of the environment and competition over glucose. We demonstrate that C. difficile's close relative Clostridium hiranonis strongly inhibits C. difficile via a pH-independent mechanism. While increasing the initial density of C. difficile can increase its abundance in the assembled community, the 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 that feature a combination of mechanisms including species richness, environment acidification, and resource competition.

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Inclusive single photon spectra have been measured in the transverse momentum (p T ) range from a few MeV/c up to approximately 1 GeV/c at various nucleon-nucleon center of momentum rapidities (y NN ) in the interval from Ϫ2.4Ͻy NN Ͻϩ0.5 in 18 GeV/c p-Be and p-W collisions. These distributions were used to estimate the inclusive p T and rapidity distributions for 0 production over approximately the same kinematic range. The measured photon spectra are compared with the expected distribution of photons from 0 decays and hadronic bremsstrahlung in order to search for new sources of ''soft'' photons at low transverse momentum. The results indicate no anomalous sources of soft photons in either p-Be or p-W interactions at these energies. The p-W data at forward angles set a limit on any excess of low p T photons at Ͻ2.65 times hadronic bremsstrahlung at the 99% C.L. ͓S0556-2813͑96͒06110-9͔