O0079 CRYPTOSPORIDIOSIS IN SUCKLING RATS: IMPACT ON GROWTH, INTESTINAL ABSORPTION AND PROTEIN SYNTHESIS

Abstract

Introduction:Cryptosporidium parvum is a parasitic protozoa increasingly appreciated as a cause of intestinal malabsorptive syndrome in patients with AIDS and in young children. The aim of this study was to explore the amino acid absorption and its metabolic consequences during cryptosporidiosis in an acute experimental model both at the peak of infection and after parasite clearance. Methods: Four-day-old Sprague-Dawley rats were inoculated by gavage with 106 oocysts of C. parvum. The rats were killed at the age of 12 days (peak of the infection) and 21 days (spontaneous clearance of the parasite). Weight, body composition, liver and gastrocnemius protein fractional synthesis rate (Pfsr) were measured. Leucine and glutamate fluxes, and glutamate (EAAT3) and oligopeptide (PEPT1) transporters mRNA levels were quantified both in the distal small intestine, preferential site of C. parvum implantation, and in the proximal small intestine, free of parasite, using Ussing chambers and RT-PCR, respectively. Results: At day 12, body weight was reduced in infected animals compared with controls (16.3 ± 5.2 vs 27.3 ± 1.0 g; p<0.01) with a decrease in both lean body mass and adipose tissue. This alteration was associated with a decrease in leucine and glutamate fluxes across the intestinal mucosa both in the proximal (−47% and −34%, respectively) and distal (−43% and −32%, respectively) parts. Pfsr was reduced in the liver (−15%) and the gastrocnemius (−20%). EAAT3 mRNA was decreased all along the small intestine (−49% and −28%, respectively). In contrast, PepT1 mRNA was increased in the proximal and distal small intestine (+19% and +16%, respectively). At day 21, body weight remained reduced in infected animals (37.8 ± 8.0 vs 47.8 ± 4.2 g, p<0.01) whereas leucine and glutamate fluxes normalized and Pfsr increased in the liver (+11%) and the gastrocnemius (+22%) of formely infected rats compared to controls. PepT1 expression normalized but the decrease in EAAT3 mRNA persisted (−31% and −46% in the proximal and distal small intestine, respectively). Conclusion: Impact and consequences of cryptosporidiosis appear to be far greater than generally appreciated. C. parvum infection induces a major amino acid malabsorption without any up-regulation neither in the proximal small intestine nor after spontaneous clearance of the parasite, contributing to malnutrition and failure to thrive. A nutritional support both precocious and beyond parasite clearance seems therefore of importance to limit lasting impairment in growth that may follow C. parvum infection. Regarding to the resistance of PepT1 expression, peptide feeding may be of value to enhancing intestinal nitrogen absorption.