Investigating the impact of the gut microbiota on intestinal helminth pathogenesis in order to identify novel treatment strategies
Mericien Venzon, MPhil; Ritika Das, PhD; E. Jane Albert Hubbard, PhD; and Ken Cadwell, PhD
Skirball Institute of Biomolecular Medicine, NYU School of Medicine
Department of Pathology, NYU School of Medicine
Department of Microbiology, NYU School of Medicine
Helminths are parasitic worms that affect billions of people worldwide. In the Philippines alone, prevalence among school-aged children—whom experience the greatest morbidity and mortality—was over 67% in 2001. Even with the inception of mass drug administration programs, the most recent prevalence estimates are still around 45%, totaling over 10 million affected children. This is largely due to the fact that the nematode whipworm Trichuris trichiura, a gastrointestinal helminth, is highly drug resistant. Standard treatment is less than 50% effective. As co-inhabitants of the host cecum, investigating gut microbe contributions at key whipworm life stages may reveal new treatment strategies and therapeutic targets. The nematode C. elegans is a well-characterized, non-parasitic model organism. Both members of Nematoda, we hypothesized that microbial factors that promote C. elegans reproduction may also be important for the Trichuris life cycle. We identified five genes in the Keio E. coli library as essential for C. elegans fertility. We then characterized the effect of these mutants at two life stages of Trichuris—egg hatching and sexual maturation—by developing methods to quantify egg hatching in vitro and fecundity in germ-free mice mono-colonized with these E. coli strains. Our data have revealed crucial roles for eutN and eutD, E. coli ethanolamine utilization pathway genes. This is the first time a role for gut bacteria metabolism has been implicated in helminth host infection.
Keywords: global health, microbiome, helminths