Abstract
OBJECTIVES: 1) To assess the polyphenol metabolites including microbial-derived metabolites after acute and 4-week red raspberry (RRB) supplementation with and without fructo-oligosaccharide (FOS) prebiotic; 2) to evaluate the gut microbiome for possible metagenomic biomarkers of lean and obese individuals with prediabetes and insulin resistance (PreDM) in response to RRB and FOS supplementation. METHODS: In a randomized, 4-week crossover clinical trial, subjects (n = 36: PreDM, n = 26; metabolically-healthy reference group, n = 10) consumed RRB (1 cup fresh equivalence) or RRB with 8 g FOS per day for 4 weeks separated by 4-week washout. Body composition, metabolic panel, polyphenol metabolites and gut microbiome were evaluated every 4 weeks for 12 weeks using standard clinical assessment protocols, ultra-high-pressure liquid chromatography-triple quadrupole and fecal metagenomic analysis with whole-metagenome shotgun sequencing, respectively. Statistical analysis was performed using, LEfSe, STAMP and SAS. RESULTS: Pre-supplementation, PreDM group was characterized by overabundant Blautia obeum and Blautia wexlerae, which positively correlated with measures of insulin resistance (P < 0.05). The obese PreDM subgroup (n = 15) compared to lean PreDM (n = 11) were characterized by lower abundance of Bifidobacterium spp., such as Bifidobacterium longum, which negatively correlated with waist and trunk fat% (P < 0.05). RRB supplementation significantly increased Clostridium orbiscindens (P = 0.044), a bacterium with polyphenol metabolizing capability, which negatively correlated with cholesterol ratio. Adding FOS to RRB significantly increased Bifidobacterium spp. in all participants (P < 0.05) and reduced B. obeum and B. wexlerae in PreDM. Over 170 RRB polyphenol metabolites, e.g., parent anthocyanins, urolithins, phenolic acids, γ-valerolactones and their glucuronide, sulfate, methyl conjugates were detected in plasma and urine and preliminary data suggests select metabolites increased over the supplementation period. CONCLUSIONS: Compositional characteristics of gut microbiome shifted by incorporating combination of RRB and FOS daily in the diet. The data provide possible insight on the role of gut microbiome on clinical markers and polyphenol metabolite pools. FUNDING SOURCES: Funds were provided by the National Processed Raspberry Council.