Evidence for the absence of an intestinal adaptive mechanism to compensate for C. parvum -induced amino acid malabsorption in suckling rats

Abstract

In order to assess the impact of Cryptosporidium parvum on host intestinal physiology, we investigated absorption of the two principal amino acids in dam's milk (leucine, glutamate), using Ussing chambers and RT-PCR analyses. Experiments were performed in both heavily (ileum) and mildly (duodenum) infected segments of the small intestine at the peak of infection [day 8 post-infection (PI)] and after spontaneous clearance of the parasite (day 17 PI). At day 8 PI, amino acid fluxes across the mucosa were decreased throughout the small intestine (P<0.01) and EAAT3 mRNA expression was reduced ( from -49% to -28%). At day 17 PI, leucine and glutamate fluxes were normalized but the decrease in EAAT3 mRNA levels persisted (from -31% to -46%). Our results demonstrate that cryptosporidiosis induces major amino acid malabsorption involving the entire small intestine which is not counterbalanced by any up-regulation, even after spontaneous clearance of the parasite.

Cryptosporidium parvumIsolate-Dependent Postinfectious Jejunal Hypersensitivity and Mast Cell Accumulation in an Immunocompetent Rat Model

“…in NoIinfected rats than in IoI-infected rats. Our findings are consistent with observations of the impact of distal ileal C. parvum infection on rat growth due to an altered amino acid transport in the entire small intestine (9,14,31,52,53).…”

“…were killed for histocytological examination. Pieces from the distal jejunum or ileum (heavily infected segment) were fixed in 10% formalin and embedded in paraffin (52).…”

Evidence for intestinal heterogenic expression of di-tripeptides transporter PepT1 during experimental cryptosporidiosis in neonatal rats

“…Previously we developed a model of acute cryptosporidiosis in the suckling rat, in which C. parvum induces marked villous atrophy, reduced amino acid absorption, and impaired growth and muscular protein synthesis, thus leading to growth failure, as observed during natural infection (Capet et al 1999;Topouchian et al 2003Topouchian et al , 2005. As the main products of protein digestion in the gut lumen are dipeptides and tripeptides rather than amino acids, we evaluated their absorption in our model.…”

Cryptosporidium infection impairs growth and muscular protein synthesis in suckling rats

“…In this model, parasite load was maximal on day 8 post infection (PI) and decreased thereafter, no oocyst being detected by day 12-14 PI . In rat pups, C. parvum infection resulted in villous atrophy and crypt hyperplasia and was responsible for nutrient malabsorption, affecting the entire small intestine, (Capet et al 1999;Topouchian et al 2001Topouchian et al , 2003Barbot et al 2003). Body weight was reduced in infected animals on day 8 PI, and a significant difference with control animals was still evident on day 17 PI, although spontaneous clearance of the parasite had occurred at that time.…”