In a 12-week randomized trial, older overweight adults who consumed blueberry powder daily saw a shift in gut bacteria—but not in their cholesterol or insulin resistance markers, highlighting the complexity of translating microbiome changes into metabolic health benefits.

Study: Effects of Blueberry Consumption on Fecal Microbiome Composition and Circulating Metabolites, Lipids, and Lipoproteins in a Randomized Controlled Trial of Older Adults with Overweight or Obesity: The BEACTIVE Trial. Image Credit: Lucky Project / Shutterstock

In a recent study published in the journal Nutrients, researchers in the United States investigated the impact of regular blueberry consumption on the fecal microbiota of older adults (over 60 years) who were overweight or obese.

They conducted a randomized controlled trial involving 55 participants, randomly assigned in nearly equal numbers to receive either the equivalent of 1.5 cups of blueberries daily (as lyophilized blueberry powder; ‘blueberry group’) or an equivalent placebo (‘placebo group’). The study employed high-throughput 16S rRNA sequencing to characterize changes in their fecal microbiota following 12 weeks of this regimen.

Study findings revealed that, while neither the blueberry group nor the placebo group demonstrated changes in fecal microbiota composition over the study duration, the blueberry group showed significant enrichment in their Coriobacteriales incertae sedis populations. However, no significant differences were detected in overall microbiome composition or diversity. These bacteria facilitate the absorption and metabolism of dietary polyphenols.

Of the 48 who completed the trial, microbiome analysis was performed on 38 participants (17 blueberry, 21 placebo), as some samples were incomplete or excluded. The final analysis revealed that Coriobacteriales incertae sedis was enriched in approximately 71% of participants in the blueberry group, while no such enrichment occurred in the placebo group.

Despite this microbial shift, the blueberry group did not exhibit statistically significant improvements in most cardiometabolic biomarkers. In contrast, the placebo group experienced reductions in LDL-C, non-HDL-C, total cholesterol, large LDL particles, and ApoB. These changes may have reflected the effects of the structured exercise regimen included in the trial design, rather than a placebo effect per se.

The placebo group also showed a statistically significant increase in trimethylamine N-oxide (TMAO), a gut-derived metabolite associated with cardiovascular risk, while the blueberry group exhibited a non-significant reduction.

Background

Dietary polyphenols, such as anthocyanins, are naturally occurring plant bioactives known for their antioxidant, cell-signaling, and anti-inflammatory properties. Commonly found in phytonutrient-rich fruits and vegetables, including blueberries, these bioactives have been found to significantly reduce the risk of cardiometabolic diseases, particularly in overweight and obese individuals (body mass index [BMI] ≥ 25 to 32 kg/m²).

Recent parallel research highlights the role of the fecal microbiome in governing the health and well-being of its hosts (humans), with microbiome composition and relative abundance observed to strongly determine the host’s resistance or susceptibility to several inflammatory and metabolic diseases, such as diabetes and obesity.

Interestingly, in murine (rodent) model systems, researchers have discovered a positive feedback loop between dietary polyphenols and fecal microbiota – increased dietary polyphenol concentrations enhance fecal microbiota structure, which in turn leads to improved polyphenol uptake and better glycemic control. While some human studies have shown blueberry-induced microbiome modulation, there remains a paucity of data in older, sedentary, overweight populations.

“Lifestyle interventions that are practical, non-invasive, and unlikely to interact with common comorbidities and their treatments can be especially beneficial for older adults, who often face a variety of health challenges.”

About the study

The present study aims to address this knowledge gap by evaluating the impact of regular (12-week) blueberry consumption on fecal microbiome composition and structure, as well as indicators of cardiovascular disease (CVD) risk, including lipid metabolism and gut-derived metabolites.

Study data were obtained from the Blueberry Enhances Activity and Cognition Through Increased Vascular Efficiency (BEACTIVE) cohort, a 12-week, randomized, placebo-controlled trial that incorporated both blueberry supplementation (in the form of blueberry powder consumed daily) and exercise.

Study participants underwent baseline screening to ensure they were aged 60 years or older, led sedentary lifestyles (less than 30 minutes of moderate physical activity per week), and were overweight or obese (BMI ≥ 25 to 32 kg/m²).

Participants were randomly assigned to either the blueberry group (18 g of lyophilized blueberry powder, consumed twice daily) or the placebo group (equivalent quantity of placebo powder). Both cohorts were subjected to weekly exercise classes to increase their baseline step count by 750 steps per month during the study.

Study measurements and data collection included baseline blood pressure measures, cognitive performance evaluations, and blood and stool sample collections at weeks 0 and 12. Additionally, participants were required to maintain 3-day dietary records, which were queried through validated questionnaires (modified DHQ-III).

Collected stool samples were subjected to 16S rRNA sequencing to identify fecal microbiome composition and relative bacterial abundance. Blood (plasma) samples were subjected to nuclear magnetic resonance (NMR) spectroscopy to quantify circulating lipoprotein profiles, choline, betaine, and trimethylamine N-oxide (TMAO).

Statistical analyses included the estimation of alpha and beta diversity indices for fecal microbiota, Bray–Curtis dissimilarity matrices, and permutational multivariate analysis of variance (PERMANOVA) to compare results between and within cohorts (week 0 versus week 12).

Study findings

Of the 55 randomized participants, 48 completed the 12-week study; microbiome analysis was completed for 38 of these individuals (17 blueberry, 21 placebo). 41% and 57% of blueberry and placebo group participants were female, respectively. The two cohorts did not differ significantly in any baseline metrics of interest.

Fecal 16S rRNA sequencing revealed both cohorts to be indistinguishable at baseline. Surprisingly, at the end of the 12-week study, almost all participants (n = 36 of 38) retained the same fecal microbiota diversity as measured individually at baseline (Bray–Curtis dissimilarity indices). No significant within- or between-group changes in overall microbiome diversity were observed.

However, significant differences were observed in the bacterial abundances of the blueberry group, while the placebo group remained essentially unchanged. Notably, Coriobacteriales incertae sedis concentrations significantly increased (in 70.6% of blueberry group participants) alongside more subtle increases in 10 other taxa.

In post-prandial samples, enrichment of Coriobacteriales incertae sedis was associated with modest reductions in large LDL particles and improvements in isoleucine levels, diabetes risk index (DRI), and lipoprotein insulin resistance index (LP-IR) scores, although these associations were exploratory and not statistically robust.

These microbial changes in the blueberry group were not accompanied by statistically significant improvements in most circulating metabolic markers. In fact, the placebo group demonstrated more favorable lipid profile changes, including reductions in LDL-C, total cholesterol, non-HDL-C, total LDL-P, large LDL-P, and ApoB.

The blueberry group showed only reductions in HDL particle counts and ApoA-I. Importantly, the study was not powered to detect causal relationships between microbial changes and cardiometabolic outcomes, and these observed correlations should be interpreted as exploratory.

Conclusions

The authors suggest that the observed increases in Coriobacteriales incertae sedis—a group of bacteria involved in polyphenol metabolism—may represent an adaptive response to enhance blueberry polyphenol digestion and absorption. They emphasize that further studies with larger sample sizes are needed to clarify the implications of these microbiome shifts for cardiometabolic risk in older adults.