Importance of Poorly Absorbed Polyphenols for the Mitigation of Gastrointestinal Inflammation by Cocoa

The US cocoa and chocolate industries are economically important. Cocoa contains large amounts of monomeric polyphenols and polymeric proanthocyanidins (PaCs). These compounds exist in both a free (ExPP) form and bound to cell material (NonExPP) and have varying bioavailability. Whereas monomeric ExPP are absorbed from the small intestine, PaCs with higher degree of polymerization (HmwPaCs) and NonExPP are poorly absorbed. These compounds reach the lower gastrointestinal (GI) tract and interact with GI tissues and/or are metabolized by microflora to systemically-available metabolites. Cocoa polyphenols can mitigate GI inflammation in vivo, however, whether these GI-related health effects are due to the systemically-available polyphenols, the interaction between unabsorbed polyphenols and GI tissues, the microbial metabolites, or a combination of these remains unclear. We hypothesize that HmwPaCs and NonExPPs, which have low bioavailability, are primarily responsible for the anti-inflammatory effects of cocoa in the GI tract. We will (1) assess the bioaccessibility of cocoa polyphenol fractions and their microbial metabolites in vitro, (2) determine the efficacy of these fractions in mouse models of GI inflammation, and (3) determine the importance of microbe-derived metabolites for modulation of GI inflammation. This research will provide insight into which polyphenolic fractions are critical for the anti-inflammatory effects of cocoa and probe the underlying mechanisms of action. This work will aid in identifying compounds that may be used as health-related quality control markers to aid processors in maximizing the health-benefits of their products.