Enteric Helminths Promote Salmonella Coinfection by Altering the Intestinal Metabolome

Intestinal helminth infectionsoccur pre dominantly in regions where exposure to enteric bacterial pathogens is also common. Helminth infectionsinhibit host immunity against microbial pathogens, which has largely been attributed to the induction of regulatory or type 2 (Th2) immune responses. Here we demonstrate an additional three-way interaction in which helminth infectionalters the metabolic environment of the host intestine to enhance bacterial pathogenicity. We show that an ongoing helminth infectionincreased colonization by Salmonella independently of T regulatory or Th2 cells. Instead, helminth infectionaltered the metabolic profile of the intestine, which directly enhanced bacterial expression of Salmonella pathogenicity island1 (SPI-1) genes and increased intracellular invasion. These data reveal a novel mechanism by which a helminth-modified metabolome promotes susceptibility to bacterial co-infection.