<i>Ex Vivo</i> Interaction Between Human Gut Microbiota and Artemisinin: A Multi-Omics Perspective

<i>Artemisia</i> is a plant genus historically used in Ayurveda and traditional Chinese medicine for its diverse pharmacological properties. Among the many phytochemicals found in <i>Artemisia</i> species, artemisinin is notable for its antimalarial activity. This compound is commonly isolated from Artemisia annua and is known to be biotransformed by fungi such as <i>Aspergillus</i>. However, there is limited knowledge on whether the gut microbiota can mediate artemisinin's biotransformation. To address this gap, this study explores for the first time the association between human gut microbiota and artemisinin-derived metabolites across three <i>Artemisia</i> species herbal extracts and purified artemisinin. Our findings describe the first sulfated artemisinin (C₃H₆NO₃S) potentially modified by bacteria Romboutsia sedimentorum and Citrobacter freundii. Thus, we highlight how a multiomics approach to natural products can reveal interactions between <i>Artemisia</i> species and the gut microbiota. This understanding can enhance the knowledge of artemisinin metabolism in the human gut and contribute to the development of novel, effective therapeutic strategies.