Gut Microbiome Metagenomics in Lean and Obese Individuals with Prediabetes and After Dietary Supplementation with Red Raspberry Fruit and Fermentable Fibers

Abstract Objectives Metagenomic analysis of the human gut microbiome is a rich dataset for discovery of possible biomarker discovery linking molecular and genomic data of resident microbial communities to host factors such as diet and clinical indices of disease risk. The objectives of this research are to: 1) characterize the structural and functional capacity of the gut microbiome of individuals with prediabetes and insulin resistance (PreDM), including relationship to body adiposity; 2) assess the influence of fruit supplementation, specifically red raspberries (RRB), a source of dietary fiber and tannins, on metagenomic biomarkers, 3) assess whether adding fructo-oligosaccharide (FOS), a known prebiotic fiber, would augment the dietary fruit effect. Methods In a randomized, 4-week treatment crossover clinical trial, subjects (n = 36: PreDM, n = 26; metabolically-healthy Reference group, n = 10) consumed RRB (1 cup fresh equivalence) daily or RRB with 8g FOS daily for 4 weeks separated by 4-week washout. DNA extracted from stool samples were assessed using whole-metagenome shotgun sequencing at week 0 for the PreDM and Reference groups and then after RRB vs. RRB + FOS supplementation. Results Blautia obeum (P = 0.02) and Blautia wexlerae (P < 0.001) were overly abundant characterizing the PreDM gut. Among PreDM, the obese subgroup (n = 15) were characterized by overabundant Bacteroides vulgatus and underabundant Bifidobacterium longum compared with PreDM lean group (n = 11) (P < 0.05). RRB supplementation increased Clostridium orbiscindensin all participants (P = 0.04), whereas adding FOS significantly increased Bifidobacterium spp.in all participants (P < 0.05), and reduced B. obeum (P = 0.04) and B. wexlerae (P = 0.03) in PreDM group. Conclusions Distinguishing compositional characteristics of gut microbiome were evident among metabolically at risk individuals, and dietary strategies incorporating fruit/RRB with prebiotics/FOS revealed possible microbial biomarkers for clinical indices related to adiposity. Funding Sources Funds were provided by the National Processed Raspberry Council.