A One-Week Elderberry Juice Intervention Augments the Fecal Microbiota and Suggests Improvement in Glucose Tolerance and Fat Oxidation in a Randomized Controlled Trial

Abstract

Obesity is a costly and ongoing health complication in the United States and globally. Bioactive-rich foods, especially those providing polyphenols, represent an emerging and attractive strategy to address this issue. Berry-derived anthocyanins and their metabolites are of particular interest for their bioactive effects, including weight maintenance and protection from metabolic aberrations. Earlier findings from small clinical trials suggest modulation of substrate oxidation and glucose tolerance with mediation of prospective benefits attributable to the gut microbiota, but mixed results suggest appropriate anthocyanin dosing poses a challenge. The objective of this randomized, placebo-controlled study was to determine if anthocyanin-dense elderberry juice (EBJ) reproduces glucoregulatory and substrate oxidation effects observed with other berries and if this is mediated by the gut microbiota. Overweight or obese adults (BMI > 25 kg/m²) without chronic illnesses were randomized to a 5-week crossover study protocol with two 1-week periods of twice-daily EBJ or placebo (PL) separated by a washout period. Each treatment period included 4 days of controlled feeding with a 40% fat diet to allow for comparison of measurements in fecal microbiota, meal tolerance testing (MTT), and indirect calorimetry between test beverages. Eighteen study volunteers completed the study. At the phylum level, EBJ significantly increased Firmicutes and Actinobacteria, and decreased Bacteroidetes. At the genus level, EBJ increased Faecalibacterium, Ruminococcaceae, and Bifidobacterium and decreased Bacteroides and lactic acid-producing bacteria, indicating a positive response to EBJ. Supporting the changes to the microbiota, the EBJ treatment significantly reduced blood glucose following the MTT. Fat oxidation also increased significantly both during the MTT and 30 min of moderate physical activity with the EBJ treatment. Our findings confirm the bioactivity of EBJ-sourced anthocyanins on outcomes related to gut health and obesity. Follow-up investigation is needed to confirm our findings and to test for longer durations.

Keywords: berry anthocyanins; fecal microbiome; functional foods; insulin and glucose homeostasis; meal tolerance test; obesity; substrate oxidation.

Figure 1

CONSORT (Consolidated Standards of Reporting Trials) diagram. One participant was excluded from analyses due to withdrawing from the study.

Figure 2

Blood glucose (A) and insulin (B) concentrations by time following a meal tolerance test including either elderberry juice or placebo treatments. EBJ, elderberry juice; PL, placebo. n = 18.

Figure 3

Non-metric multidimensional scaling (NMDS) plot comparing the four groups. EBJ1 or PL1, baseline fecal samples, EBJ2 or PL2, post-intervention fecal samples.

Figure 4

Changes in microbial population at phylum level; (A): changes in relative abundance of Bacteroidetes and Firmicutes comparing treatments EBJ1, EBJ2, PL1, and PL2, (B): changes in the relative abundance of Actinobacteria comparing treatments EBJ1, EBJ2, PL1, and PL2; (C): changes in relative abundance of Bacteroidetes and Firmicutes comparing combined EBJ and PL treatments; (D): changes in the relative abundance of Actinobacteria, Proteobacteria, and Verrucomicrobia comparing combined treatments EBJ and PL. EBJ1 or PL1, baseline fecal samples, EBJ2 or PL2, post-intervention fecal samples. Pair-wise comparisons without a common letter are significantly different, p < 0.05. Pair-wise comparisons with an asterisk are marginally different, p < 0.1.

Figure 5

Changes in gut microbial population at genus level; (A): changes in relative abundance of Faecalibacterium and Ruminococcaceae comparing combined EBJ and PL; (B): changes in the relative abundance of Lactobacillus, Lactococcus, and Streptococcus comparing combined treatments EBJ and PL; (C): changes in relative abundance of Prevotella, Alistipes, and Bacteroides comparing combined EBJ and PL treatments; (D): changes in the relative abundance of Bifidobacterium comparing combined treatments EBJ and PL. EBJ, elderberry juice; PL, placebo. Pair-wise comparisons without a common letter are significantly different, p < 0.05. Pair-wise comparisons with an asterisk are marginally different, p < 0.1.