Gut microbiota-mediated conversion of mangiferin to norathyriol alters short chain fatty acid and urate metabolism

Mangiferin (MAN), a natural C-glycosylxanthone, is recognized for its health-promoting effects in traditional medicinal preparations. However, its poor bioavailability and limited intestinal permeability restrict its direct biological activity in vivo. Previous studies have suggested a potential bacterial breakdown of MAN into norathyriol (NOR), an aglycone with significantly higher bioavailability and absorption. Yet, the prevalence of MAN-metabolizing microbes, the presence of MAN or NOR within the gut microbial community, and their effects on the composition and metabolic activity of the gut microbiome remain unclear. In this study, fecal samples from healthy adult volunteers treated with MAN revealed its conversion to NOR, with interindividual variation attributed to the uncultured bacterial strain CAKRHR01 sp934339005. While MAN had minimal impact on microbial composition and metabolic activity, NOR treatment significantly increased pH, reduced overall bacterial cell counts, and selectively suppressed short-chain fatty acid-producing bacteria, including Faecalibacterium prausnitzii as well as urate consumers, such as Enterocloster bolteae. These findings underscore the potential of NOR to modulate gut microbial activity and highlight the importance of understanding microbiome-mediated metabolism when assessing the health implications of phytochemicals.