Gut microbiota-derived propionate by a high-salt diet modulates brain tumor microenvironment

Abstract

however, it can also modulate gut microbiota leading to changes in microbiome-derived metabolites. In this study, I found that a HSD altered the composition of gut microbiota, including a large increase in the Bacteroides vulgatus population, resulting in the exacerbation of glioma brain tumors. Levels of propionate, a short-chain fatty acid (SCFA) produced by B. vulgatus, were elevated in the gut of mice fed a HSD. I determined that propionate administration induced glioma exacerbation as determined by reduced survival. In addition, propionate induced pseudohypoxia in glioma cells resulting in enhanced TGF-β signaling. Within the tumor microenvironment (TME), this elevated TGF-β signaling promoted the differentiation of monocyte-derived macrophages into an anti-inflammatory subset. These results indicate that a metabolite derived from the gut microbiota that is elevated under conditions of a HSD has a negative impact on the brain tumor microenvironment resulting in reduced survival in a murine glioma model.

A high-salt diet (HSD) is a common westernized diet that affects various organs via osmolality enhancement