Moderate to Severe Ulcerative Colitis Results in Differential Metabolism of Cranberry Polyphenols by the Colon Microbiome Ex Vivo

Abstract

Abstract Objectives The microbiome plays a major role in polyphenol metabolism, producing metabolites that are bioavailable and potentially more bioactive than the polyphenol compounds from which they are derived. A consequence of ulcerative colitis (UC) is a ‘dysbiotic’ microbiome characterized by decreased species diversity, which may impact an individual's capability to metabolize polyphenols into bioavailable metabolites. The objective was to compare the microbial metabolism of cranberry polyphenols between fecal donors that were healthy or had moderate to severe UC to determine if dysbiosis effects polyphenol metabolism. Methods Fecal samples were donated by volunteers with or without moderate to severe UC (n = 9). Fecal samples were cultured anaerobically within 2 hours of defecation in the presence of A and B type proanthocyanidins, flavonols and anthocyanins extracted from cranberry powder. Aliquots were taken at 5 different time points over a 48-hour period and the resulting polyphenol metabolites were quantified via LC-ESI-MS/MS using SRM and authentic standards. 16S rRNA metagenomics analysis was also utilized to assess changes in the composition of the fecal microbiota. Results After 6 hours, healthy individuals produced 2.50, 20.1 and 5.25-fold higher (P < 0.05) concentrations of 3-(3-hydroxyphenyl)propionic acid, 3,4-dihydroxyphenylacetic acid and 3’,4’-dihydroxyphenyl-gamma-valerolactone, respectively. Healthy individuals continued to have significantly higher concentrations of these metabolites over the 48-hour period. UC microbiomes did not produce 3-hydroxyphenylacetic until after 48 hours, suggesting that the microbiome of those with UC may have significantly lower de-hydroxylase activity. Healthy microbiomes contained higher (P < 0.05) proportions of Ruminococcaceae, which could explain their ability to produce higher concentrations of cranberry polyphenol metabolites. Conclusions The microbiome of individuals with UC produces significantly lower cranberry polyphenol metabolites than healthy microbiomes. These results suggest that efficiency of polyphenol metabolism is dependent on health status of the colon and polyphenols could be potential biomarkers of colon health. Funding Sources Ocean Spray Cranberries, Inc, Middleborough, MA.