Effect of Caging on Cryptosporidium parvum Proliferation in Mice

Abstract

Cryptosporidiosis is an enteric infection caused by several protozoan species in the genus Cryptosporidium (phylum Apicomplexa). Immunosuppressed mice are commonly used to model this infection. Surprisingly, for a pathogen like Cryptosporidium parvum, which is readily transmitted fecal-orally, mice housed in the same cage can develop vastly different levels of infection, ranging from undetectable to lethal. The motivation for this study was to investigate this phenomenon and assess the association between the severity of cryptosporidiosis and the fecal microbiota. To this aim, the association between severity of cryptosporidiosis and caging (group caged vs. individually caged) and between the microbiota taxonomy and the course of the infection was examined. In contrast to mice caged in groups of four, a majority of mice caged individually did not excrete a detectable level of oocysts. Microbiota α diversity in samples collected between three days prior to infection and one day post-infection was negatively correlated with the severity of cryptosporidiosis, suggesting a causal negative relationship between microbiota diversity and susceptibility to C. parvum.

Fecal microbiota impacts development of Cryptosporidium parvum in the mouse

“…Because of the potential for caging conditions to affect the course of cryptosporidiosis 15 , 20 , in this study we included only individually caged animals. The goals of these analyses were twofold; the first set of analyses focused on the entire dataset of 108 samples collected between day − 3 post-infection and the end of each experiment.…”

“…Such interventions could act on enterocytes but also on goblet cells to promote mucin secretion. The goal of the experiments described here and published previously 15 aim to identify molecular mechanisms explaining the interaction between microbiota metabolism and the course of cryptosporidiosis. To distinguish between cause and effect, microbiota collected no later than 3 days post-infection were analyzed separately from samples collected later in the experiment.…”

“…In a previous publication focused on the effect of caging on the course of cryptosporidiosis 15 , samples from three experiments (Table 1 , #35, #37, #38) with group caged and individually caged mice were analyzed to explore the effect of caging. All samples analyzed in the present contribution originated from mice caged individually, including those from experiments 35, 37 and 38 described previously 15 . CD-1 mice between four and six weeks of age were purchased from Charles River Laboratories (Wilmington, MA, USA).…”

“…Although much research has focused on elucidating host-microbiota interaction in the healthy and infected GI tract 9 – 12 , the feasibility of harnessing this knowledge to prevent the most severe consequences of intracellular enteric pathogens has to our knowledge not been extensively explored. The interdependence between enterocyte and microbiota motivates our search 13 – 15 for nutritional interventions capable of impacting C. parvum proliferation as low-cost alternatives to future vaccines and drugs.…”

“…An emerging and less explored drawback of modelling the human microbiota in the mouse is the unexplained difference in the taxonomy of the native intestinal microbiota in different mouse strains and different lots of mice. 16S amplicon sequencing has begun to uncover vastly different intestinal microbiota in mice used in different studies, even when mice originated from the same vendor 15 , 18 , 19 . This unintended variability has the potential to negatively affect reproducibility, particularly given the large number of physiological and behavioral phenotypes impacted by the gut ecology.…”