Fig. 3

Application of MDSINE to an experimental dataset evaluating the dynamics of Clostridium difficile infection in gnotobiotic mice. Germ-free mice were pre-colonized with the GnotoComplex microflora, a mixture of human commensal bacterial type strains chosen to capture the phylogenetic diversity and key physiologic capabilities of a native gut microflora. After the commensal microbiota were allowed to establish for 28 days, mice were infected with C. difficile spores and monitored for an additional 28 days. Throughout the experiment, 26 fecal samples per mouse were collected and interrogated via high-throughput 16S rRNA sequencing to determine abundances of species and 16S rRNA qPCR using universal primers to estimate the total bacterial biomass present. a Predicted directed microbe–microbe interaction network. Edge thickness denotes the magnitude of the evidence favoring presence of the interaction (Bayes factors [35]); only edges with strong evidence (Bayes factor ≥10) are displayed. b Predicted stable combinations of strains for each possible size of sub-community that optimally inhibit C. difficile colonization. Each row depicts the sub-community (combination of commensal strains) of a given size that is predicted to stably colonize the gut in the absence of the pathogen and is predicted to maximally inhibit C. difficile infection at the experimental end point (28 days). CDI median predicted median concentration of C. difficile at 28 days, CDI mad predicted absolute deviation of the median of the C. difficile concentration at 28 days