Microbiota tryptophanase activity and Cryptosporidium parvum proliferation

Protozoa in the genus Cryptosporidium infect intestinal epithelial cells. The profile of the fecal microbiota has been shown to impact the proliferation of Cryptosporidium parvum in a mouse model of cryptosporidiosis, motivating research to understand the mechanisms underlying this interaction. Given the lack of effective drugs and vaccines, pro- or prebiotics capable of increasing resistance to parasite proliferation in the gastro-intestinal tract should be considered as alternative treatment options. To understand if and how the intestinal microbiota could be harnessed to increase resistance against cryptosporidiosis, we tested if C. parvum proliferation in the mouse responds to oral administration of Escherichia coli. This bacterium was chosen because it encodes tryptophanase, an enzyme which converts tryptophan into indole. This molecule has been shown to inhibit C. parvum in culture and in mice. To track E. coli colonization and survival, an ampicillin-resistant E. coli strain expressing green fluorescent protein was given by oral gavage. Excretion of green fluorescent bacteria in the feces was highly variable among mice, a phenomenon which is also observed with C. parvum. A positive correlation between fecal output of the E. coli probiotic and C. parvum was observed. This observation is significant because it indicates that mechanisms inhibiting or promoting colonization of the GI tract by pathogens or commensals are not specific to C. parvum but impact two microorganisms as different as E. coli and C. parvum. Consistent with an effect of the microbiota on cryptosporidiosis, the pre-infection microbiota taxonomy and inferred microbiota metabolic function were significantly associated with mouse susceptibility to C. parvum. This effect was unrelated to the administration of E. coli. Contrary to the observed inhibitory effect of indole on C. parvum, microbiota indole production potential was positively correlated with C. parvum fecal output. Finally, the effect of cryptosporidiosis on the microbiota was characterized by an expansion of facultative anaerobes, particularly Gammaproteobacteria.