Intestinal short-chain fatty acid composition does not explain gut microbiota-mediated effects on malaria severity

Malaria is a devastating disease resulting in significant morbidity and mortality, especially in the developing world. Previously, we showed that the gut microbiome modulates severity of malaria in mice, though the exact mechanism was unknown. One well-studied mechanism by which the intestinal microbiota exerts an effect on host health is by synthesis of short-chain fatty acids (SCFAs). SCFAs have pleiotropic effects on the host, including modulating the immune system and altering susceptibility to pathogens. The objective of the current work was to explore if gut microbiota-mediated resistance and susceptibility to malaria in mice is through differential production of SCFAs. Of the eight detected SCFAs, only propionic acid (C3) was different between two groups of resistant and two groups of susceptible mice, with higher levels in feces of susceptible mice compared to resistant mice. Nevertheless, subsequent analysis revealed no robust correlation between malaria severity and levels of fecal propionic acid. In spite of the broad effect of SCFAs on host physiology, including host immunity, this study shows that gut microbiota-mediated modulation of malaria severity in mice is independent of fecal SCFA levels. Additionally, our data indicates that intestinal SCFAs do not function as biomarkers for prediction of malaria disease severity.