ArticlebioRxiv : the preprint server for biology2025
Gut microbiota gate host exposure to cholinesterase inhibitors from dietary Solanums.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
16 authors.
Funding
Abstract
Dietary plants are molecularly rich but the fates of these compounds post-ingestion and their implications for human health are largely unknown. Here, we systematically characterized the major chemical contributions of widely consumed Solanum species (nightshades) to the human metabolome. Using untargeted metabolomics, we found that a series of steroidal alkaloids resulting from glycoalkaloids tomatine, solanine, and chaconine are dominant diet-derived compounds in systemic circulation following ingestion of tomato and potato. By comparing serum and tissue metabolomes of colonized and microbiome-depleted mice, we determined that the gut microbiota modifies these compounds extensively, altering their absorption and gating host exposure. By screening the metabolic products in human urine and stool samples, we established that steroidal glycoalkaloid metabolism varies inter-individually in a population. Furthermore, using a collection of representative human commensal type strains, we found that a limited set of strains is responsible for steroidal glycoalkaloid metabolism, with the chemical output of a community determined by its strain-level composition. These findings enabled the rational design of complex synthetic microbial communities that controlled host exposure to steroidal alkaloid metabolites
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Registered trials
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