Bovine lactoferrin decreases cholera-toxin-induced intestinal fluid accumulation in mice by ganglioside interaction

PLoS One. 2013 Apr 8;8(4):e59253. doi: 10.1371/journal.pone.0059253. Print 2013.


Secretory diarrhea caused by cholera toxin (CT) is initiated by binding of CT's B subunit (CTB) to GM1-ganglioside on the surface of intestinal cells. Lactoferrin, a breast milk glycoprotein, has shown protective effect against several enteropathogens. The aims of this study were to determine the effect of bovine-lactoferrin (bLF) on CT-induced intestinal fluid accumulation in mice, and the interaction between bLF and CT/CTB with the GM1-ganglioside receptor. Fluid accumulation induced by CT was evaluated in the mouse ileal loop model using 56 BALB/c mice, with and without bLF added before, after or at the same time of CT administration. The effect of bLF in the interaction of CT and CTB with GM1-ganglioside was evaluated by a GM1-enzyme-linked immunosorbent assay. bLF decreased CT-induced fluid accumulation in the ileal loop of mice. The greatest effect was when bLF was added before CT (median, 0.066 vs. 0.166 g/cm, with and without bLF respectively, p<0.01). We conclude that bLF decreases binding of CT and CTB to GM1-ganglioside, suggesting that bLF suppresses CT-induced fluid accumulation by blocking the binding of CTB to GM1-ganglioside. bLF may be effective as adjunctive therapy for treatment of cholera diarrhea.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cattle
  • Chlorides / pharmacology
  • Cholera Toxin / metabolism*
  • Dose-Response Relationship, Drug
  • Enterotoxins / biosynthesis
  • Escherichia coli / drug effects
  • Escherichia coli / growth & development
  • Escherichia coli / metabolism
  • Female
  • Ferric Compounds / pharmacology
  • G(M1) Ganglioside / metabolism
  • Gangliosides / metabolism*
  • Intestinal Mucosa / metabolism*
  • Intestines / drug effects
  • Intestines / pathology
  • Lactoferrin / metabolism*
  • Lactoferrin / pharmacology
  • Mice
  • Protein Binding / drug effects
  • Receptors, Cell Surface / metabolism


  • Chlorides
  • Enterotoxins
  • Ferric Compounds
  • Gangliosides
  • Receptors, Cell Surface
  • ganglioside receptor
  • G(M1) Ganglioside
  • Cholera Toxin
  • Lactoferrin
  • ferric chloride