Gut microbiota dictate metabolic Fate of Curcumin in the colon

The metabolic fate of dietary bioactive compounds play critical roles in their health effects. Herein, we determined the metabolic fate of curcumin in the gastrointestinal (GI) tract of mice after long-term dietary administration of curcumin for 6 weeks. Our results demonstrated that in the GI tract curcumin underwent phase I metabolism to yield three metabolites, namely tetrahydro-curcumin (M1), hexahydro-curcumin (M2) and octahydro-curcumin (M3). Curcumin and these phase I metabolites then were subject to phase II metabolism to yield their corresponding conjugated phase II metabolites. The above-mentioned metabolism of curcumin occurred in the stomach but to a much less extent than that in the small intestine. Only phase II metabolites of curcumin could be found in the small intestine (i.e., conjugated forms of curcumin, M1 and M2), while only phase I metabolites of curcumin could be detected in the cecum and colon (i.e., M1 and M2). This suggested that gut microbiota might be responsible for the deconjugation of phase II metabolites that converted them back to the corresponding phase I metabolites in the cecum and colon. Indeed, anaerobic fermentation of phase II metabolites (isolated from the small intestine of curcumin-fed mouse) by both mouse and human fecal bacteria deconjugated them to yield phase I metabolites. Moreover, fecal bacteria were able to transform curcumin to yield M1, M2, and M3, and they can further breakdown these four compounds to yield fission products such as ferulic acid. To confirm the role of gut microbiota in biotransformation of curcumin, curcumin-fed mice were treated with or without dextran sulfate sodium (DSS) in the drinking water (DSS is an agent capable of altering gut microbiota, and we confirmed the altered microbiota by DSS via next generation sequencing of fecal microbiota). Analyses of colonic content by LC/MS demonstrated that in comparison with the control mice, DSS-treated mice had a completely different curcumin metabolite profile in the colon, i.e., much higher levels of phase II metabolites and much lower levels of fission products of curcumin. Overall, our results demonstrated that composition of gut microbiota had a profound impact on the biotransformation of curcumin in the colon, which might have a significant influence on the health effects of dietary curcumin, especially in the colon. Support or Funding InformationThis study was partially supported by fund from USDA.