Researchers explore blueberries as a tool to support microbiota in early life

Feeding blueberry powder to infants during the transition to solid foods showed promising effects on gut microbiota diversity, highlighting a potential new strategy for supporting lifelong health.

Study: Introducing blueberry powder as one of the first complementary foods changes the gut microbiota composition and diversity in U.S. human milk-fed infants: a double-blind, randomized controlled trial. Image Credit: Radowitz / Shutterstock

In a recent study published in the journal Frontiers in Nutrition, researchers in the United States investigated the effect of daily blueberry powder intake during complementary feeding on gut microbiota development.

Complementary feeding, i.e., the transition from liquid diets to solid foods, typically starts around six months of age. It is a critical phase for infant development, characterized by rapid changes in nutrient needs and dietary intake. This dynamic phase is also pivotal for shaping the composition of the gut microbiota, which is susceptible to modulation and immature in infancy.

Early gut microbiota manipulation could influence immune system development, disease risks, and long-term health outcomes. Therefore, complementary feeding represents an opportune time to promote a healthier microbiota development. While diet influences the gut microbiota in adults, how specific complementary foods affect gut microbiota development is unclear.

About the study

In the present study, researchers evaluated the effects of blueberry powder as one of the first complementary foods on the development of the gut microbiota in infants. This randomized, placebo-controlled trial included human milk-fed infants with full-term birth, minimal prior complementary food exposure, and no previous antibiotic exposure. Participants were randomized to the blueberry or placebo group.

At the baseline visit to the research facility (at five or six months of age), participants’ caregivers completed a questionnaire on family and feeding history, demographics, parental height and weight, medications during pregnancy, gestational weight gain, parity, maternal alcohol and smoking status, allergy history, and stooling patterns. Baseline demographic analyses showed statistically significant differences between groups in income and ethnicity.

Infant anthropometric measurements and stool and blood samples were also collected at baseline. Home visits at seven, nine, and 11 months of age involved infant stool sample collections, anthropometric measurements, and health and allergy questionnaires. Baseline procedures were repeated at the final visit to the research facility at 12 months of age. At each visit, participants received packets of their assigned powder.

Freeze-dried highbush blueberry powder, equivalent to about two ounces of blueberries, was provided to the blueberry group. The placebo group received isocaloric powder. The powder was fed as a puree that forms when mixed with liquid. Caregivers were asked to provide one packet daily from baseline to 12 months and complete a daily intake log. In addition, caregivers completed three-day diet records before each visit.

Stool samples were used for gut microbial profiling by a broad-range amplification and sequence analysis of 16S rRNA genes. Z-scores were calculated for infant length, weight, and head circumference using the World Health Organization growth chart standards. Chi-square and independent t-tests were used to compare participant growth z-scores and demographics. Linear mixed effects models were used for microbiota analysis with exploratory analyses prespecified at p = 0.1 and adjusted for mode of delivery and sequencing batch.

Findings

In total, 61 participants, 31 in the placebo group and 30 in the blueberry group, completed the study. About 70% of infants had no formula intake from birth until enrolment, and among those with formula exposure before enrolment, it was less than a week for 70%. The proportion of infants receiving human milk during the study did not differ between groups.

There were no significant differences between groups in energy, fiber, and macronutrient intakes based on solid foods and study powders; human milk and formula were excluded from intake analyses by design. At 12 months, more infants in the blueberry group consumed formula than in the placebo group; however, this difference was not statistically significant. Formula intake volume was not different between groups.

At each visit, length for age (LAZ), weight for length, weight for age (WAZ), and head circumference for age z-scores were not significantly different between groups. While LAZ was greater in the blueberry group at seven months, the difference did not persist at subsequent visits. Across the cohort, WAZ and LAZ remained below population medians throughout the study, with mean baseline values of LAZ = –0.96 and WAZ = –0.49. Notably, participants showed a lower than population median LAZ and WAZ throughout the study.

The mode of delivery and sequencing batch were significantly associated with baseline composition of the gut microbiota. Alpha and beta diversity measures showed significant changes over time. The three alpha diversity indices: Shannon diversity, evenness, and richness, increased with age in both groups. Group×Age terms trended toward greater alpha diversity in the blueberry group (p ≈ 0.085–0.087), while beta diversity showed no significant group effect.

The blueberry group showed increased abundances of Subdoligranulum, Flavonifractor, Veillonaceae, and Butyricicoccus over time compared to the placebo group. Conversely, four taxa showed reduced abundances in the blueberry group over time: Romboutsia, Actinomyces, Escherichia, and Streptococcus. These represented trends over time; only Actinomyces showed an FDR-adjusted p-value trending toward significance (0.056).

Reported adherence to packet consumption was lower in the blueberry compared with the placebo group at 11 and 12 months, which may have attenuated detectable effects.

Conclusions

Taken together, introducing blueberry powder as one of the first complementary foods may exert additive benefits on gut microbiota development in human milk-fed infants. The gut microbiota alpha diversity increased over time in both groups. However, the blueberry diet tended to increase alpha diversity more than the placebo diet, although findings were exploratory.

Key limitations include the relatively small sample size, uncontrolled dietary intake beyond the study powders, the inability to quantify human milk intake, baseline demographic imbalances, and the lack of long-term follow-up to assess health outcomes.

Trial registration: NCT05006989. Funding: National Institute of Diabetes and Digestive and Kidney Diseases and the U.S. Highbush Blueberry Council.

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