The Reciprocal Interactions Between Red Raspberry Polyphenols and Gut Microbiome Composition: Preliminary Finding

Red raspberry (Rubus idaeus L.) contains a variety of polyphenols, absorbed in different forms (parent compounds, degradants or microbial metabolite molecules), subject to xenobiotic metabolism in the intestine, liver, and/or kidney, forming methylate, glucuronide, and sulfate conjugated metabolites. Consistent exposure of certain polyphenols to the gut microbiota may act as prebiotic-like substances feeding the beneficial gut bacteria and changing the gut microbiome composition and function. The dichotomy between the biotransformation of polyphenols into their metabolites by gut microbiota and the modulation of gut microbiome composition by polyphenols is hypothesized to contribute to positive health outcomes. The present study examined the regular consumption of red raspberry puree (RRB) and/or fructo-oligosaccharide (FOS) on gut microbiome composition and subsequent bioavailability of red raspberry polyphenols in healthy volunteers. An 8-week pilot study served as a feasibility study to collect multiple biological specimens for method development. An ultra high-performance liquid chromatography (HPLC) coupled with electrospray ionization quadrupole time of flight (QTOF) and triple quadrupole (QQQ) mass spectrometer were used to identify and quantify the phenolic compounds in red raspberry puree, plasma and urine samples. The sequencing of the 16S ribosomal RNA gene was utilized to study the gut microbiome composition in fecal samples. The red raspberry puree contained 148.55 +/- 5.43 mg/100 g fresh weight (FW) polyphenols. Chronic RRB and/or FOS exposure influenced gut microbiome composition: at the phylum level, 4-week FOS (8 g/d), RRB (125 g/d), or FOS plus RRB (8 and 125 g/d, respectively) exposures all decreased Firmicutes and increased Bacteroidetes; at the genus level, 4-week FOS, RRB, or FOS plus RRB exposures all boosted Bacteroides and diminished Blautia; and the increased Akkermansia was only observed after RRB exposure. Chronic RRB and/or FOS exposure also altered the observed RRB polyphenol metabolites: the parent anthocyanins, such as cyanidin 3-O-sophoroside, were lower in plasma and urine after adaptation to RRB, while the production of urolithin A glucuronide increased after FOS, RRB and FOS plus RRB exposures; an effect hypothesized to be related to the altered composition and metabolic activity of the gut microbiota. Overall, these data suggest chronic RRB and/or FOS exposure influenced gut microbiome composition and subsequently increased gut microbial metabolites.