Appearance of green tea compounds in plasma following green tea consumption is modulated by the gut microbiome in mice

Studies have suggested that phytochemicals in green tea have systemic anti-inflammatory and neuroprotective effects. However, the mechanisms behind these effects are poorly understood, possibly due to differential metabolism of phytochemicals due to varying gut microbiome composition. To unravel this complex relationship, our team utilized a novel combined microbiome analysis and metabolomics approach applied to low diversity, pseudo-germ-free (GF) and human colonized (HU) gnotobiotic mice treated with an acute dose of powdered matcha green tea. A total of 20 GF mice received 10 distinct human fecal slurries, for an n=2 mice per human gut microbiome; 9 mice remained GF throughout the experiment. We used untargeted metabolomics to identify green tea compounds that were found in GF and HU mouse plasma following acute dosing of green tea. 16s ribosomal RNA sequencing was performed on feces of all mice at study end to assess microbiome composition. We found multiple green tea compounds associated with microbiome presence and diversity, and we also detected strong associations between green tea compounds and specific taxa in the gut. Many of these compounds are bioactive in the host, including spiramycin and lactiflorin. Additionally, some of the physiologically relevant green tea compounds are likely derived from plant-associated microbes, highlighting the importance of considering food products as meta-organisms. Overall, we describe a novel workflow for discovering relationships between individual food compounds and composition of the gut microbiome.