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

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, ß-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.

Physicochemical interactions with (-)-epigallocatechin-3-gallate drive structural modification of celiac-associated peptide α2-gliadin (57-89) at physiological conditions.

(-)-Epigallocatechin-3-gallate (EGCG), a major phenolic constituent of tea, has been shown to have biological activity within inflammatory pathways involved with food allergies and intolerances. Proposed mechanisms for this effect include sequestration and structural modification of immunostimulatory proteins as a result of interactions with EGCG. The present study employs biophysical techniques including dynamic light scattering, circular dichroism and nuclear magnetic resonance to elucidate the likely mechanism(s) by which EGCG interacts with α2-gliadin (57-89) (α2g), an immunodominant peptide in celiac disease pathogenesis. We demonstrate that EGCG interacts with α2g in a multi-phase reaction driven by non-specific binding, resulting in the formation of polydisperse EGCG/α2g complexes which induce changes in peptide structure. We also show that these interactions occur at a range of pH levels associated with digestion, including pH 2.0, 6.8 and 7.5. Based on previous reports of binding specificity of enzymes and antigen presenting cells in celiac disease pathogenesis, our results provide foundational support for EGCG to prevent recognition of immunostimulatory gliadin epitopes by the body and thus prevent the inflammatory and autoimmune response associated with celiac disease.

Green Tea Polyphenols Mitigate Gliadin-Mediated Inflammation and Permeability in Vitro.

SCOPE: Green tea, a polyphenol-rich beverage, has been reported to mitigate a number of inflammatory and hypersensitivity disorders in laboratory models, and has been shown to moderate pathways related to food allergies in vitro. The present study investigates the impact of decaffeinated green tea extract (GTE) on the digestion of gliadin protein in vitro and the effect of physical interactions with GTE on the ability of gliadin to stimulate celiac disease-related symptoms in vitro. METHODS AND RESULTS: Complexation of GTE and gliadin in vitro is confirmed by monitoring increases in turbidity upon titration of GTE into a gliadin solution. This phenomenon is also observed during in vitro digestion when gliadin is exposed to the digestive proteases pepsin and trypsin. SDS-PAGE and enzymatic assays reveal that GTE inhibits digestive protease activity and gliadin digestion. In differentiated Caco-2 cell monolayers as a model of the small intestinal epithelium, complexation of gliadin with GTE reduces gliadin-stimulated monolayer permeability and the release of interleukin (IL)-6 and IL-8. CONCLUSION: There are potential beneficial effects of GTE as an adjuvant therapy for celiac disease through direct interaction between gliadin proteins and green tea polyphenols.