From high-salt diet to cancer immunity: gut microbiota and immune system interactions and their mechanisms

Abstract

High-salt diet (HSD) has traditionally been studied in the context of cardiovascular disease, hypertension, and kidney disease. Increasing evidence now suggests that salt intake may also influence cancer immunity through direct effects on immune cells and indirect effects mediated by the gut microbiota. HSD can regulate inflammatory activation in T cells, macrophages, NK cells, and other immune populations. It can also reshape gut microbial composition and alter microbial metabolites, including short-chain fatty acids (SCFAs), bile acids (BAs), and tryptophan (Trp) metabolites. These changes may affect immune homeostasis, inflammatory signaling, and the tumor microenvironment. Current evidence suggests that the HSD-microbiota-immune axis has context-dependent roles in cancer biology. In some experimental settings, HSD may enhance antitumor immune responses, whereas chronic exposure may promote inflammation, immune exhaustion, microbial dysbiosis, and tumor progression. In this review, we summarize how HSD interacts with the gut microbiota and immune system, discuss its potential bidirectional effects on cancer initiation and progression, and highlight future directions for diet-microbiota-immune interventions in cancer prevention and therapy.