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Background/Objectives: The complementary feeding period is a critical window for shaping infant diet, gut microbiota, and immune development. While allergic symptoms often emerge in the first year of life, the effects of specific foods, such fruits, on infant allergy symptoms, inflammation, immunity and associated microbiota remain unclear. This study aimed to assess the impact of daily blueberry consumption during the complementary feeding period on allergy-related symptoms, immune biomarkers, and gut microbiota in breastfed U.S. infants.

Methods: In a double-blind, randomized, placebo-controlled trial, infants from the Denver metro area were assigned to receive up to 10 g/day of freeze-dried blueberry powder or an isocaloric placebo from 5 to 12 months of age. Stool, blood, and caregiver-reported allergy-related symptom data were collected at baseline and study end.

Results: Of the 76 infants enrolled, 61 completed the study (Blueberry: n = 30; Placebo: n = 31). While more infants in the blueberry group had allergy-related symptoms at baseline, they had significantly different longitudinal symptom trajectories than the placebo (p = 0.05), showing a greater resolution rate of symptoms by study end. Pro-inflammatory serum IL-13 levels were significantly reduced (p = 0.035) and anti-inflammatory IL-10 levels borderline increased (p = 0.052) in the blueberry group. However, changes in allergy symptoms were not significantly associated with IL-10 or IL-13. The relative abundances of Lacticaseibacillus, Blautia, and Peptostreptococcaceae at 12 months were negatively correlated with IL-10, while Lactobacillus, Clostridiaceae, and Megasphaera were positively associated. IL-13 was positively associated with Citrobacter and negatively associated with Anaerostipes and Blautia.

Conclusions: The consumptio9n of blueberries as an early complementary food may improve resolution of allergy symptoms, modulate immune biomarkers, and promote beneficial shifts in gut microbiota during infancy. Future research should aim to identify the specific bioactive components of blueberries responsible for these effects and explore the potential of other complementary foods to favorably influence developing biological systems involved in microbiota and immune development.