THE RECIPROCAL INTERACTIONS BETWEEN RED RASPBERRY POLYPHENOLS AND GUT MICROBIOME COMPOSITION: PRELIMINARY FINDINGS
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Red raspberry (Rubus idaeus L.) contains a variety of polyphenols including anthocyanins and ellagitannins. Red raspberry polyphenols absorbed in different forms (parent compounds, degradant or microbial metabolite molecules) are 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 purée (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, including two 4-week chronic treatments and 3 postprandial days, served as a feasibility study and mechanism 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 purée, plasma and urine samples. Fecal samples were used for the metagenomic study. The sequencing of the 16S ribosomal RNA gene was utilized to study the gut microbiome composition. The red raspberry purée 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 (the main microbial-derived metabolite of ellagitannins) increased after FOS, RRB and FOS plus RRB exposure; 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.