Co-infection with hookworm and schistosomes is a common phenomenon in sub-Saharan Africa, as well as in parts of South America and southeast Asia. As a first step towards understanding the metabolic response of a hookworm-schistosome
co-infection in humans, we investigated the metabolic consequences of
co-infection in an animal model, using a nuclear magnetic resonance (NMR)-based metabolic profiling technique, combined with multivariate statistical analysis. Urine and serum samples were obtained from hamsters experimentally infected with 250 Necator americanus infective L(3) and 100 Schistosoma japonicum cercariae simultaneously. In the
co-infection model, similar worm burdens were observed as reported for single
infection models, whereas metabolic profiles of
co-infection represented a combination of the altered metabolite profiles induced by single
infections with these two parasites. Consistent differences in metabolic profiles between the co-infected and non-infected control hamsters were observed from 4 weeks p.i. onwards. The predominant metabolic alterations in co-infected hamsters consisted of depletion of
amino acids, tricarboxylic acid cycle intermediates (e.g.
citrate and
succinate) and
glucose. Moreover, alterations of a series of gut microbial-related metabolites, such as decreased levels of
hippurate,
3-hydroxyphenylpropionic acid,
4-hydroxyphenylpropionic acid and
trimethylamine-N-oxide, and increased concentrations of
4-cresol glucuronide and
phenylacetylglycine were associated with
co-infection. Our results provide a first step towards understanding the metabolic response of an animal host to multiple
parasitic infections.