Antimicrobials - Entamoeba

Amebiasis, caused by the protozoan Entamoeba (E.) histolytica, is the third leading cause of death by parasitic diseases, surpassed only by malaria and schistosomiasis. Worldwide, approximately 50 million people are infected with E. histolytica, resulting in nearly 100,000 deaths annually.

E. histolytica is transmitted by the fecal-oral route through contaminated food or water and is often endemic in regions with poor hygiene. Infection is initiated through ingestion of the semi-dormant cyst form of the parasite, which passes through the stomach and small intestine to reach the colon, where it differentiates into motile trophozoites that can colonize and invade the host’s mucosa and cause dysentery. In rare cases, trophozoites metastasize from the colon and cause extra-intestinal abscesses mainly in liver, but also in lung or brain. Colonization and invasion require the attachment of trophozoites to the host’s mucosa. Trophozoites that cannot attach are carried downstream and are excreted with the feces without causing disease.

Breast-fed infants are at lower risk to acquire E. histolytica infections than formula-fed infants. This could be explained by a reduced exposure to contaminated water that might be used to prepare formula and/or by amebicidal components in human milk. Our data indicate that some HMO are part of the anti-amebic defense in human milk (Jantscher-Krenn et al. 2012).

Our in vitro results show that physiological concentrations of isolated, pooled HMO detach E. histolytica by more than 80%. In addition, HMO rescue E. histolytica-induced destruction of human intestinal epithelial HT29 cells in a dose-dependent manner. The cytoprotective effects were structure-specific. Lacto-N-tetraose with its terminal galactose rescued up to 80% of the HT29 cells, while HMO with fucose alpha1-2-linked to the terminal galactose had no effect.

Galactooligosaccharides (GOS), which also contain terminal galactose and are currently added to infant formula to mimic some of the beneficial effects of HMO, completely abolished E. histolytica attachment and cytotoxicity at 8 mg/mL. Although our results need to be confirmed in vivo, they may provide one explanation for why breast-fed infants are at lower risk for E. histolytica infections. HMO and GOS are heat tolerant, stable, safe and in the case of GOS, inexpensive, which could make them valuable candidates as alternative preventive and therapeutic anti-amebic agents.

Our lab now aims to investigates whether the results translate to protection against E. histolytica infections in humans of all ages.