Project description:The composition of the gut microbiota is directly associated with response to checkpoint inhibitors in cancer. How diet impacts the gut microbiota and downstream immune response to cancer remains unclear. Here, we show that consumption of a common artificial sweetener, sucralose, supports microbial dysbiosis, restricts T cell metabolism and function, and limits immunotherapy response in cancer. Microbial dysbiosis is associated with a reduction in Arginine, and amino acid supplementation or fecal microbiome transfer completely restores T cell function and immunotherapy response. Thus, artificial sweetener consumption destabilizes the gut microbiota, resulting in compromised T cell function and ablated immunotherapy response in cancer.
Project description:Sucralose is an artificial sweetener commonly used in food and drinks to increase food palatability and control total calorie content. While it is approved for human consumption by both the EFSA and the FDA, recent reports have questioned the safety of long-term consumption of s. in this study, we show that high doses of sucralose affect immune responses in different mouse models of autoimmunity, infection, and cancer. Similarly, sucralose impedes proper t cell proliferation and polarization in vitro. Mechanistically, sucralose dampens signals downstream the TCR resulting in decrease calcium flux upon TCR activation.
Project description:Non-nutritive sweeteners like sucralose are consumed by billions of people. While animal and human studies have demonstrated a link between synthetic sweetener consumption and metabolic dysregulation, the mechanisms responsible remain unknown. Here we use a diet supplemented with sucralose to investigate the long-term effects of sweet/energy imbalance. In flies, chronic sweet/energy imbalance promoted hyperactivity, insomnia, glucose intolerance, enhanced sweet taste perception and a sustained increase in food and calories consumed, effects that are reversed upon sucralose removal. Mechanistically, this response was mapped to the ancient insulin, catecholamine, and NPF/NPY systems and the energy sensor AMPK, which together comprise a novel neuronal starvation response pathway. Interestingly, chronic sweet/energy imbalance promoted increased food intake in mammals as well, and this also occurs through an NPY-dependent mechanism. Together our data show that chronic consumption of a sweet/energy imbalanced diet triggers a conserved neuronal fasting response and increases the motivation to eat.
Project description:We studied the membrane protein compositions of Streptococcus pneumoniae WT and scRNA mutant strains, with or without the CSP1 induction into competence state.