Insights in the Recalcitrance of Theasinensin A to Human Gut Microbial Degradation

[Image: see text] Due to low bioavailability of dietary phenolic compounds in small intestine, their metabolism by gut microbiota is gaining increasing attention. The microbial metabolism of theasinensin A (TSA), a bioactive catechin dimer found in black tea, has not been studied yet. Here, TSA was extracted and purified for in vitro fermentation by human fecal microbiota, and epigallocatechin gallate (EGCG) and procyanidin B2 (PCB2) were used for comparison. Despite the similarity in their flavan-3-ol skeletons, metabolic fate of TSA was distinctively different. After degalloylation, its core biphenyl-2,2′,3,3′,4,4′-hexaol structure remained intact during fermentation. Conversely, EGCG and PCB2 were promptly degraded into a series of hydroxylated phenylcarboxylic acids. Computational analyses comparing TSA and PCB2 revealed that TSA’s stronger interflavanic bond and more compact stereo-configuration might underlie its lower fermentability. These insights in the recalcitrance of theasinensins to degradation by human gut microbiota are of key importance for a comprehensive understanding of its health benefits.