Cranberry Extract and Polyphenol Metabolites Modulate Luminal and Mucosal Microbiome

Cranberry polyphenols (PPs) are associated with various health benefits, which can be exerted by the known parent compounds and/or through related metabolites resulting from microbial metabolization. Metabolite levels and profile/composition are often subject to extensive inter-individual variability, and many aspects of the relevant bidirectional interactions of PPs with the individual gut microbiota are still elusive. Both undigested and predigested cranberry extract were tested, next to procyanidin A2 and hyperoside controls, on the luminal and mucosa-associated gut microbial communities of six healthy adult donors in vitro. The composition of the microbial communities, polyphenolic substrate metabolization patterns, and microbial metabolites, including short-chain fatty acids (SCFAs), bile acids and aromatic acids, were analyzed at different timepoints. Both predigested and undigested cranberry extracts modulated the microbiota composition in all donors, albeit with individual variations. The mucosal samples responded differently than the luminal samples, and the type of extract also affected the composition of microbiota differently. Further, inter-individual differences in the metabolization patterns and metabolite production, such as 3,4 DHPPA (3,4-dihydroxyphenylpropionic acid), 3,4 DHPP-2-ol, and 3,4-dihydroxyphenyl acetic acid, were observed. SCFA production was stimulated with predigested cranberry extract. A semipolar compound analysis further showed much broader metabolic variations, both in cranberry-related metabolites, such as 4-vinylphenol and 3,4,5-trimethoxyphenylacetic acid, and in microbial metabolites such as indole-3-lactic acid. This study increases the knowledge on how individual microbiota samples are modulated upon exposure to cranberry-related PPs and how this influences their metabolic activity.