Impact of predicted microbiota tryptophanase activity on Cryptosporidium parvum proliferation

Abstract

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 and a reverse effect of the parasite on the microbiota has also been described. The mechanisms underlying this interaction are unknown. The lack of effective drugs and vaccines is motivating the search for pro- or prebiotics capable of increasing resistance to parasite proliferation in the gastrointestinal tract. To understand if and how the intestinal microbiota could be harnessed for this purpose, we tested if C. parvum proliferation in the mouse responds to oral administration of Escherichia coli. This bacterium was chosen because of its reported importance in mediating colonization resistance, because it encodes tryptophanase, an enzyme which converts tryptophan into indole, and because of the availability of an ampicillin-resistant strain expressing green fluorescent protein. Excretion of GFP+ E. coli in the feces was highly variable among mice, a phenomenon which is also observed with C. parvum. A positive correlation between fecal output of probiotic E. coli and C. parvum was observed. This finding may indicate that intestinal colonization with two microorganisms as different as E. coli and C. parvum responds to the same conditions in the GI tract. Consistent with an effect of the microbiota on cryptosporidiosis, the pre-infection microbiota taxonomic profile was predictive of mouse susceptibility to C. parvum. Contrary to the reported inhibitory effect of indole on C. parvum, microbiota indole production potential was positively correlated with C. parvum fecal output. The effect of cryptosporidiosis on the microbiota was characterized by an expansion of facultative anaerobes, particularly Gammaproteobacteria. This study is a first attempt to assess the proliferation in the mouse of a defined probiotic and quantify its effect on C. parvum development.