Dietary Polyphenols Support Akkermansia muciniphila Growth via Mediation of the Gastrointestinal Redox Environment

Abstract

Obesity and metabolic dysfunction have been shown to be associated with overproduction of reactive oxygen species (ROS) in the gastrointestinal (GI) tract, which contributes to dysbiosis or imbalances in the gut microbiota. Recently, the reversal of dysbiosis has been observed as a result of dietary supplementation with antioxidative compounds including polyphenols. Likewise, dietary polyphenols have been associated with scavenging of GI ROS, leading to the hypothesis that radical scavenging in the GI tract is a potential mechanism for the reversal of dysbiosis. The objective of this study was to investigate the relationship between GI ROS, dietary antioxidants and beneficial gut bacterium Akkermansia muciniphila. The results of this study demonstrated A. muciniphila to be a discriminant microorganism between lean (n = 7) and obese (n = 7) mice. The relative abundance of A. muciniphila was also found to have a significant negative correlation with extracellular ROS in the GI tract as measured using fluorescent probe hydroindocyanine green. The ability of the dietary antioxidants ascorbic acid, β-carotene and grape polyphenols to scavenge GI ROS was evaluated in tandem with their ability to support A. muciniphila bloom in lean mice (n = 20). While the relationship between GI ROS and relative abundance of A. muciniphila was conserved in lean mice, only grape polyphenols stimulated the bloom of A. muciniphila. Analysis of fecal antioxidant capacity and differences in the bioavailability of the antioxidants of interest suggested that the poor bioavailability of grape polyphenols contributes to their superior radical scavenging activity and support of A. muciniphila in comparison to the other compounds tested. These findings demonstrate the utility of the GI redox environment as a modifiable therapeutic target in the treatment of chronic inflammatory diseases like metabolic syndrome.