Parasitology Research

, Volume 91, Issue 3, pp 197–203

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

  • A. Topouchian
  • J. F. Huneau
  • L. Barbot
  • S. Rome
  • J. G. Gobert
  • D. Tomé
  • N. Kapel
Original Paper

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.

References

  1. Agnew DG, Lima AA, Newman RD, Wuhib T, Moore RD, Guerrant RL, Sears CL (1998) Cryptosporidiosis in northeastern Brazilian children: association with increased diarrhea morbidity. J Infect Dis 177:754–760Google Scholar
  2. Argenzio RA, Liacos JA, Levy ML, Meuten DJ, Lecce JG, Powell DW (1990) Villous atrophy, crypt hyperplasia, cellular infiltration, and impaired glucose-Na absorption in enteric cryptosporidiosis of pigs. Gastroenterology 98:1129–1140PubMedGoogle Scholar
  3. Baksheev L, Fuller PJ (2000). Humoral factors in intestinal adaptation. Trends Endocrinol Metab 11:401–405CrossRefPubMedGoogle Scholar
  4. Barbot L, Windsor E, Rome, Tricottet V, Reynès M, Topouchian A, Huneau JF, Gobert JG, Tomé D, Kapel N (2003). Intestinal peptide transporter PepT1 is over-expressed during acute cryptosporidiosis in suckling rats as a result of both malnutrition and parasite implantation. Parasitol Res 89:364–370PubMedGoogle Scholar
  5. Capet, C, Kapel N, Huneau JF, Magne D, Laikuen R, Tricottet V, Benhamou Y, Tome D, Gobert JG (1999) Cryptosporidium parvum infection in suckling rats: impairment of mucosal permeability and Na+-glucose cotransport. Exp Parasitol 91:119–125CrossRefPubMedGoogle Scholar
  6. Casemore DP (1990) Epidemiological aspects of human cryptosporidiosis. Epidemiol Infect 104:1–28PubMedGoogle Scholar
  7. Checkley W, Gilman RH, Epstein LD, Suarez M, Diaz JF, Cabrera L, Black RE, Sterling CR (1997) Asymptomatic and symptomatic cryptosporidiosis: their acute effect on weight gain in Peruvian children. Am J Epidemiol 145:156–163PubMedGoogle Scholar
  8. Checkley W, Epstein LD, Gilman RH, Black RE, Cabrera L, Sterling CR (1998) Effects of Cryptosporidium parvum infection in Peruvian children: growth faltering and subsequent catch-up growth. Am J Epidemiol 148:497–506PubMedGoogle Scholar
  9. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159PubMedGoogle Scholar
  10. Davis KE, Straff DJ, Weinstein EA, Bannerman PG, Correale DM, Rothstein JD, Robinson MB (1998) Multiple signaling pathways regulate cell surface expression activity of the excitatory amino acid carrier 1 subtype of glutamate transporter in C6 glioma. J Neurosci 18:2475–2485PubMedGoogle Scholar
  11. Elliott DA, Clark DP (2000) Cryptosporidium parvum induces host cell actin accumulation at the host-parasite interface. Infect Immun 68:2315–2322CrossRefPubMedGoogle Scholar
  12. Fayer R, Morgan U, Upton SJ (2000) Epidemiology of Cryptosporidium: transmission, detection and identification. Int J Parasitol 30:1305–1322PubMedGoogle Scholar
  13. Fogaca H, Souza H, Carneiro AJ, Carvalho AT, Pimentel ML, Papelbaum M, Elia P, Elia C (2000) Effects of oral nutritional supplementation on the intestinal mucosa of patients with AIDS. J Clin Gastroenterol 30:77–80CrossRefPubMedGoogle Scholar
  14. Gegelashvili G, Schousboe A (1997) High affinity glutamate transporters: regulation of expression and activity. Mol Pharmacol 52:6–15PubMedGoogle Scholar
  15. Guerrant DI, Moore SR, Lima AA, Patrick PD, Schorling JB, Guerrant RL (1990) Association of early childhood diarrhea and cryptosporidiosis with impaired physical fitness and cognitive function four-seven years later in a poor urban community in northeast Brazil. Am J Trop Med Hyg 61:707–713Google Scholar
  16. Henriksen SA, Pohlenz JF (1981) Staining of cryptosporidia by a modified Ziehl–Neelsen technique. Acta Vet Scand 22:594–596PubMedGoogle Scholar
  17. Hoste H (2001) Adaptive physiological processes in the host during gastrointestinal parasitism. Int J Parasitol 31:231–244CrossRefPubMedGoogle Scholar
  18. Kanai Y, Hediger MA (1992) Primary structure and functional characterization of a high-affinity glutamate transporter. Nature 360:467–471Google Scholar
  19. Kapel N, Benhamou Y, Buraud M, Magne D, Opolon P, Gobert JG (1996) Kinetics of mucosal ileal gamma-interferon response during cryptosporidiosis in immunocompetent neonatal mice. Parasitol Res 82:664–667CrossRefPubMedGoogle Scholar
  20. Ling SC, Griffiths AM (2000) Nutrition in inflammatory bowel disease. Curr Opin Clin Nutr Metab Care 3:339–344CrossRefPubMedGoogle Scholar
  21. Lumadue JA, Manabe YC, Moore RD, Belitsos PC, Sears CL, Clark DP (1998) A clinicopathologic analysis of AIDS-related cryptosporidisis. AIDS 12:2459–2466CrossRefPubMedGoogle Scholar
  22. Maillard ME, Stevens BR, Mann GI (1995) Amino acid transport by small intestinal, hepatic and pancreatic epithelia. Gastroenterology 108:888–910PubMedGoogle Scholar
  23. Marcial MA, Madara JL (1986) Cryptosporidium: cellular localization, structural analysis of absorptive cell-parasite membrane interaction in guinea pigs, and suggestion of protozoan transport by M cells. Gastroenterology 90:583–594PubMedGoogle Scholar
  24. Molbak K, Andersen M, Aaby P, Hojlyng N, Jakobsen M, Sodemann M, Da Silva AP (1997) Cryptosporidium infection in infancy as a cause of malnutrition: a community study from Guinea-Bissau, west Africa. Am J Clin Nutr 65:149–152PubMedGoogle Scholar
  25. Mosier DA, Oberst RD (2000) Cryptosporidiosis: a global challenge Ann NY Acad Sci 916:102–111Google Scholar
  26. Pappenheimer JR (1993) On the coupling of membrane digestion with intestinal absorption of sugars and amino acid. Am J Physiol Cell Physiol 265:G409–G417Google Scholar
  27. Reeds PJ, Burrin DG, Stoll B, Jahoor F, Wykes L, Henry J, Frazer ME (1997) Enteral glutamate is the preferential source for mucosal glutathione synthesis in fed piglets. Am J Physiol 273:E408–E415PubMedGoogle Scholar
  28. Rocha F, Musch MW, Lishanskiy L, Bookstein C, Sugi K, Xie Y, Chang EB (2001) IFN-gamma downregulates expression of Na(+)/H(+) exchangers NHE2 and NHE3 in rat intestine and human Caco-2/bbe cells. Am J Physiol Cell Physiol 280:C1224–C1232PubMedGoogle Scholar
  29. Rome S, Barbot L, Windsor E, Kapel N, Tricottet V, Huneau JF, Reynes M, Gobert JG, Tomé D (2002) The regionalization of PepT1, NBAT and EAAC1 transporters in the small intestine of rats are unchanged from birth to adulthood. J Nutr 132:1009–1011Google Scholar
  30. Rossi P, Rivasi F, Codeluppi M, Catania A, Tamburini A, Righi E, Pozio E (1998) Gastric involvement in AIDS associated cryptosporidiosis. Gut 43:476–477PubMedGoogle Scholar
  31. Ruff MD, Wilkins GC (1980) Total intestinal absorption of glucose and l-methionine in broilers infected with Eimeria acervulina, E. mivati, E. maxima or E. brunetti. Parasitology 80:555–569PubMedGoogle Scholar
  32. Sims KD, Straff DJ, Robinson MB (2000) Platelet-derived growth factor rapidly increases activity and cell surface expression of the EAAC1 subtype of glutamate transporter through activation of phosphatidylinositol 3-kinase. J Biol Chem 274:5228–5327CrossRefGoogle Scholar
  33. Symons LEA (1976) Malabsorption. In: Soulsby EJL (ed) Pathophysiology of parasitic infection. Academic Press, Sydney, pp 11–21Google Scholar
  34. Topouchian A, Kapel N, Huneau JF, Barbot L, Magne D, Tomé D, Gobert JG (2001) Impairment of amino-acid absorption in suckling rats infected with Cryptosporidium parvum. Parasitol Res 87:891–896PubMedGoogle Scholar
  35. Travis WD, Schmidt K, MacLowry JD, Masur H, Condron KS, Fojo AT (1990) Respiratory cryptosporidiosis in a patient with malignant lymphoma. Report of a case and review of the literature. Arch Pathol Lab Med 114:519–522PubMedGoogle Scholar
  36. Wu G (1998) Intestinal mucosal amino acids catabolism. J Nutr 128:1249–1252PubMedGoogle Scholar
  37. Yoo D, Lo W, Goodman S, Ali W, Semrad C, Field M (2000) Interferon-gamma downregulates ion transport in murine small intestine cultured in vitro. Am J Physiol Gastrointest Liver Physiol 279:G1323–G1332PubMedGoogle Scholar
  38. Ziegler TR, Bazargan N, Galloway JR (2000) Glutamine supplemented nutrition support: saving nitrogen and saving money? Clin Nutr 19:375–377CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • A. Topouchian
    • 2
  • J. F. Huneau
    • 3
  • L. Barbot
    • 1
    • 2
  • S. Rome
    • 3
  • J. G. Gobert
    • 1
    • 2
  • D. Tomé
    • 3
  • N. Kapel
    • 1
    • 2
  1. 1.Service de Coprologie Fonctionnelle, Groupe Hospitalier Pitié–SalpêtrièreBâtiment La Force—Division Vincent de PaulParisFrance
  2. 2.Laboratoire de Biologie Animale et Parasitaire, Faculté des Sciences Pharmaceutiques et BiologiquesUniversité René DescartesParisFrance
  3. 3.UMR 914 Physiologie de la Nutrition et du Comportement AlimentaireInstitut National Agronomique Paris–GrignonParisFrance

Personalised recommendations