What is it about?
Many diseases such as Inflammatory Bowel Disease, metabolic and psychiatric disorders are associated with an imbalance of gut microbial species, named dysbiosis, that actively participates to the development and severity of the pathologies. The origin of dysbiosis is still unclear but involves defects in a specialized intestinal epithelial cell type, Paneth cells, that are key regulators of gut microbiota composition, and are dysfunctional in obese or IBD patients. We show here that dysbiosis initiation relies on a cross talk between altered Paneth cells and tuft cells, key epithelial sentinels known to initiate type 2 mucosal immunity following infections with parasites or bacteria. We identify a multistep mechanism responsible for dysbiosis initiation that involves a tripartite relationship between Paneth cells, microbiota-derived succinate and tuft cells.
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Why is it important?
This study reveals a novel function of tuft cells in promoting dysbiosis in a context of altered Paneth cells. We highlight an additional role of Paneth cells, beside their crucial properties in microbe regulation, since we demonstrate here that they are essential to prevent inappropriate activation of tuft cells and deleterious dysbiosis by inhibiting the growth of microbes producing the metabolite succinate.
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This page is a summary of: Cross talk between Paneth and tuft cells drives dysbiosis and inflammation in the gut mucosa, Proceedings of the National Academy of Sciences, June 2023, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2219431120.
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