Resistant Starch\nNanoparticles Induce Colitis through\nLysosomal Exocytosis in Mice

Resistant starch (RS) is present in various natural and\nprocessed\nfoods as well as medications. It has garnered significant attention\nfrom both scientists and consumers due to its notable health benefits.\nHowever, there is a limited understanding of how RS particles are\nabsorbed at the cellular level and their metabolic behavior, resulting\nin a lack of clarity regarding the intestinal safety implications\nof prolonged RS exposure. Here, we demonstrate that rice-derived RS\nnanoparticles (RSNs) can lead to colitis in mice by triggering lysosomal\nexocytosis. The research shows that RSNs enter the cells through macropinocytosis\nand clathrin- and caveolin-mediated endocytosis and activate TRPML1\nthereafter, causing the release of lysosomal calcium ions. This, in\nturn, triggered the TFEB signaling pathway and thus upregulated the\nlysosomal exocytosis level, leading to lysosomal enzymes to be released\nto the intestinal lumen. As a result, a decreased number of intestinal\ngoblet cells, diminished tight junction protein expression, and imbalanced\nintestinal flora in mice were observed. These damages to the intestinal\nbarrier ultimately led to the occurrence of colitis. Our study offers\nimportant insights into the cellular bioeffects and detrimental effects\non intestinal health caused by RS particles and emphasizes the need\nto re-evaluate the safety of long-term RS consumption.