title: Giardia lamblia: the role of conjugated and unconjugated bile salts in killing by human milk.
abstract: Killing of Giardia lamblia trophozoites by nonimmune human milk in vitro is dependent upon the presence of cholate which activates the milk bile salt-stimulated lipase to cleave fatty acids from milk triglycerides. In the present studies, conjugated bile salts, which predominate in vivo, displayed striking differences from unconjugated bile salts in ability to support killing by milk. Human milk killed greater than 99% of the parasites in the presence of cholate, but not glycocholate or taurocholate. In contrast, after brief sonication which disrupts milk fat globules, milk killed G. lamblia after addition of either conjugated or unconjugated bile salts. Whereas cholate stimulated milk lipase to cleave triglycerides of either unsonicated or sonicated human milk, glycocholate or taurocholate stimulated lipolysis only in sonicated milk. Since the concentration of bile salts in the small intestine fluctuates, the effect of this variable on killing was examined. Each bile salt at and above its critical micellar concentration increased Giardia survival of human milk probably because it sequestered released fatty acids in micelles. This partial protection could be overcome by increasing the milk concentration. Human hepatic and gall bladder bile and artificial bile also activated human milk to kill at low concentrations but partly protected the parasite at higher concentrations. These studies show that conjugated bile salts can activate the bile salt-stimulated lipase of sonicated human milk to release fatty acids; and kill G. lamblia. Conversely, bile salts in concentrations above their critical micellar concentration sequester fatty acids and interfere with killing. Thus, nonimmune host secretions such as milk and bile may affect the course of infection by G. lamblia.
mesh_terms: D000818:Animals; D001646:Bile / Q000502:physiology; D001647:Bile Acids and Salts / Q000494:pharmacology*; D019826:Cholic Acid; D002793:Cholic Acids / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005872:Giardia / Q000502:physiology*; D005999:Glycochenodeoxycholic Acid / Q000494:pharmacology; D006000:Glycocholic Acid / Q000494:pharmacology; D006801:Humans; D008049:Lipase / Q000378:metabolism; D008823:Micelles; D008895:Milk, Human / Q000201:enzymology / Q000502:physiology*; D013010:Sonication; D013656:Taurocholic Acid / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; D002793:Cholic Acids; D005230:Fatty Acids, Nonesterified; D008823:Micelles; D014280:Triglycerides; D013656:Taurocholic Acid; D005999:Glycochenodeoxycholic Acid; D008049:Lipase; D019826:Cholic Acid; D006000:Glycocholic Acid