Malaria parasite infection compromises colonization resistance to an enteric pathogen by reducing gastric acidity.

Abstract

Malaria parasite infection weakens colonization resistance against <i>Salmonella enterica</i> serovar (<i>S.</i>) Typhimurium. <i>S.</i> Typhimurium is a member of the Enterobacterales, a taxon that increases in abundance when the colonic microbiota is disrupted or when the colonic mucosa is inflamed. However, here, we show that infection of mice with <i>Plasmodium yoelii</i> enhances <i>S.</i> Typhimurium colonization by weakening host control in the upper GI tract. <i>P. yoelii</i>-infected mice had elevated gastric pH. Stimulation of gastric acid secretion during <i>P. yoelii</i> infection restored stomach acidity and colonization resistance, demonstrating that parasite-induced hypochlorhydria increases gastric survival of <i>S.</i> Typhimurium. Furthermore, blockade of <i>P. yoelii</i>-induced TNF-α signaling was sufficient to prevent elevation of gastric pH and enhance <i>S.</i> Typhimurium colonization during concurrent infection. Collectively, these data suggest that abundance in the fecal microbiota of facultative anaerobes, such as <i>S.</i> Typhimurium, can be increased by suppressing antibacterial defenses in the upper GI tract, such as gastric acid.