Blueberry phytochemicals modulate the gut-vascular axis through microbiome-metabolome interaction.
8 affiliations
- 1Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, Utah 84112, USA. [email protected].
- 2Department of Biomedical Informatics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
- 3Plants for Human Health Institute, Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Kannapolis, NC 28081, USA.
- 4Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
- 5Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
- 6Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah 84112, USA.
- 7Office of Comparative Medicine, University of Utah, Salt Lake City, Utah 84112, USA.
- 8USDA Agricultural Research Service, Responsive Agricultural Food System Research Unit, College Station, TX 77843, USA.
Abstract
Dietary phytochemicals are metabolized by gut microbes into bioactive metabolites that mediate their physiological effects. This study investigated whether microbiome-metabolome interactions contribute to the vascular benefits of blueberry phytochemicals via the gut-vascular axis. Both conventionally raised and germ-free mice received freeze-dried blueberries via oral gavage, and plasma metabolites were analyzed at multiple time points. In other cohorts, mice were fed a standard or high-fat diet (HFD) with or without freeze-dried blueberry powder (∼1.5 human servings) and treated with or without antibiotics (Abx; to deplete gut microbes) for 12 weeks. Metabolic parameters, vascular endpoints, plasma metabolites, and the gut microbiome were assessed. Blueberry intake increased plasma blueberry-derived metabolites in conventionally raised but not germ-free mice, indicating that gut microbes are essential for metabolizing phytochemicals. This was also confirmed in Abx-treated mice. Blueberries reduced HFD-induced vascular inflammation. However, microbial depletion reduced plasma blueberry metabolites and abolished the benefits of blueberries in reducing vascular inflammation. HFD-enriched genera such as Faecalimonas were positively associated, whereas blueberry-derived metabolites (hippuric acid and 3-hydroxy hippuric acid) were negatively associated with vascular inflammation. Furthermore, Turicibacter and Clostridia UGC-014 (incertae sedis), which are enriched by dietary blueberries, were positively associated with hippuric acid. These findings provide insight into the importance of the interaction between the microbiome and metabolome in regulating the benefits of dietary phytochemicals on vascular inflammation via the gut-vascular axis.
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BibTeX
@article{babu2026blueberry,
title = {{Blueberry phytochemicals modulate the gut-vascular axis through microbiome-metabolome interaction.}},
author = {Adhini Kuppuswamy Satheesh Babu and Chrissa Petersen and Michael S Robeson and Lisard Iglesias-Carres and Henry A Paz and Juanita G Ratliff and Ying Zhong and Rickesha Bell and Kartik Shankar and Umesh D Wankhade and Andrew P Neilson and Pon Velayutham Anandh Babu},
journal = {Food \& function},
year = {2026},
month = nov,
doi = {10.1039/d6fo04275a},
url = {https://europepmc.org/article/MED/42969403},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Blueberry phytochemicals modulate the gut-vascular axis through microbiome-metabolome interaction.
AU - Adhini Kuppuswamy Satheesh Babu
AU - Chrissa Petersen
AU - Michael S Robeson
AU - Lisard Iglesias-Carres
AU - Henry A Paz
AU - Juanita G Ratliff
AU - Ying Zhong
AU - Rickesha Bell
AU - Kartik Shankar
AU - Umesh D Wankhade
AU - Andrew P Neilson
AU - Pon Velayutham Anandh Babu
PY - 2026
DA - 2026/11/02
JO - Food & function
DO - 10.1039/d6fo04275a
UR - https://europepmc.org/article/MED/42969403
AB - Dietary phytochemicals are metabolized by gut microbes into bioactive metabolites that mediate their physiological effects. This study investigated whether microbiome-metabolome interactions contribute to the vascular benefits of blueberry phytochemicals via the gut-vascular axis. Both conventionally raised and germ-free mice received freeze-dried blueberries via oral gavage, and plasma metabolites were analyzed at multiple time points. In other cohorts, mice were fed a standard or high-fat diet (HFD) with or without freeze-dried blueberry powder (∼1.5 human servings) and treated with or without antibiotics (Abx; to deplete gut microbes) for 12 weeks. Metabolic parameters, vascular endpoints, plasma metabolites, and the gut microbiome were assessed. Blueberry intake increased plasma blueberry-derived metabolites in conventionally raised but not germ-free mice, indicating that gut microbes are essential for metabolizing phytochemicals. This was also confirmed in Abx-treated mice. Blueberries reduced HFD-induced vascular inflammation. However, microbial depletion reduced plasma blueberry metabolites and abolished the benefits of blueberries in reducing vascular inflammation. HFD-enriched genera such as Faecalimonas were positively associated, whereas blueberry-derived metabolites (hippuric acid and 3-hydroxy hippuric acid) were negatively associated with vascular inflammation. Furthermore, Turicibacter and Clostridia UGC-014 (incertae sedis), which are enriched by dietary blueberries, were positively associated with hippuric acid. These findings provide insight into the importance of the interaction between the microbiome and metabolome in regulating the benefits of dietary phytochemicals on vascular inflammation via the gut-vascular axis.
SN - 2042-6496
SN - 2042-650X
ER -