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Title: Sex-specific changes in gut microbiome composition following blueberry consumption in C57BL/6J mice

Author
item WANKHADE, UMESH - Arkansas Children'S Nutrition Research Center (ACNC)
item ZHONG, YING - University Arkansas For Medical Sciences (UAMS)
item LAZARENKO, OXANA - University Arkansas For Medical Sciences (UAMS)
item CHINTAPALLI, SREE - Arkansas Children'S Nutrition Research Center (ACNC)
item PICCOLO, BRIAN - Arkansas Children'S Nutrition Research Center (ACNC)
item CHEN, JIN-RAN - Arkansas Children'S Nutrition Research Center (ACNC)
item SHANKAR, KARTIK - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/26/2019
Publication Date: 2/1/2019
Citation: Wankhade, U.D., Zhong, Y., Lazarenko, O.P., Chintapalli, S.V., Piccolo, B.D., Chen, J., Shankar, K. 2019. Sex-specific changes in gut microbiome composition following blueberry consumption in C57BL/6J mice. Nutrients. 11(2):313. https://doi.org/10.3390/nu11020313.
DOI: https://doi.org/10.3390/nu11020313

Interpretive Summary: Blueberries are considered beneficial for human health, and have been recently implicated in promoting healthy bone in studies conducted in rodent models. The effects of blueberries and specific blueberry-derived components is likely dependent on the actions of the naturally-occurring bacteria in the intestinal track (gut microbiota). In the current study, we used male and female mice to investigate the effect of blueberry supplementation on gut microbiome, and determined if these diet-microbiome interactions differ by sex. It was shown that blueberry alters the gut microbiome differentially in male and female mice. Gut microbial parameters such as alpha and beta diversity (indicators of how many types of bacteria are present), and abundances of several specific bacterial sub-types (taxa) were altered upon blueberry feeding, regardless of sex. These results provide strong evidence supporting the idea that changed microbiota can contribute to physiological changes due to blueberry feeding in mice, and that the effects can differ by sex. This forms the foundation for studies in human populations to test how feeding blueberries and other nutrient-rich fruits impacts the gut microbiota, and to assess if diet-associated changes differ in boys and girls (in children) and men and women (adults).

Technical Abstract: The antioxidant and anti-inflammatory properties of blueberries improve vascular function and insulin sensitivity. However, the bioavailability of the active compounds in blueberries is largely dependent on the gut microbiota, which may themselves be altered by blueberry components. The objective of the current study was to explore a possible sex-dependent modulation of the gut microbiota following supplementation with blueberries in adult mice. Eight-week-old C57BL/6J mice (n = 7–10/group) were provided with control or blueberry-containing diets (5% freeze-dried powder) for 4 weeks. Body weight, composition, and food intake were measured weekly. Genomic DNA was isolated from the cecal contents for 16S rRNA sequencing. Blueberry feeding decreased a-diversity (operational taxonomical unit abundance) and altered b-diversity (p < 0.05). At the phylum level, the Firmicutes to Bacteroidetes ratio was significantly lower in the blueberry-fed groups (p < 0.001), along with increased Tenericutes and decreased Deferribacteres. At the genus level, blueberry feeding led to sexually-dimorphic differences, which were associated with predicted metabolic pathways. Pathways such as fatty acid and lipid metabolism were significantly different and demonstrated a stronger association with microbes in the male. To summarize, blueberry supplementation led to sexually-dimorphic global changes in the gut microbiome, which could possibly contribute to physiological changes in mice.