Enteric helminths promote Salmonella co-infection by altering the intestinal metabolome.

J Infect Dis. 2017 Mar 25. doi: 10.1093/infdis/jix141. [Epub ahead of print]
Reynolds LA, Redpath SA, Yurist-Doutsch S, Gill N, Brown EM, van der Heijden J, Brosschot TP, Han J, Marshall NC, Woodward SE, Valdez Y, Borchers CH, Perona-Wright G, Finlay BB.

Intestinal helminth infections occur predominantly in regions where exposure to enteric bacterial pathogens is also common. Helminth infections inhibit 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 infection alters the metabolic environment of the host intestine to enhance bacterial pathogenicity. We show that an ongoing helminth infection increased colonization by Salmonella independently of T regulatory or Th2 cells. Instead, helminth infection altered the metabolic profile of the intestine, which directly enhanced bacterial expression of Salmonella pathogenicity island 1 (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.