Transplantation of an obesity-associated human gut microbiota to mice induces vascular dysfunction and glucose intolerance

• Published in: Gut microbes 2021-01, Vol.13 (1), p.1940791-1940791
• Main Authors: Trikha, S. Raj J., Lee, Dustin M., Ecton, Kayl E., Wrigley, Scott D., Vazquez, Allegra R., Litwin, Nicole S., Thomas, Keely N., Wei, Yuren, Battson, Micah L., Johnson, Sarah A., Kuhn, Kristine A., Colgan, Sean P., Gentile, Christopher L., Weir, Tiffany L.
• Format: Article
• Language: English
• Subjects: Adult; Animals; cardiovascular disease; Cohort Studies; Disease Models, Animal; endothelial function; Female; Gastrointestinal Microbiome; Germ-Free Life; Glucose Intolerance - etiology; Glucose Intolerance - physiopathology; Healthy Volunteers; Humans; Male; Mice; microbiota; Middle Aged; obesity; Obesity - complications; Obesity - microbiology; pulse wave velocity; Research Paper; Vascular Diseases - etiology; Vascular Diseases - physiopathology; vascular function
• ISSN: 1949-0976; 1949-0984
• DOI: 10.1080/19490976.2021.1940791

Recent preclinical data suggest that alterations in the gut microbiota may be an important factor linking obesity to vascular dysfunction, an early sign of cardiovascular disease. The purpose of this study was to begin translation of these preclinical data by examining whether vascular phenotypes in humans are transmissible through the gut microbiota. We hypothesized that germ-free mice colonized with gut microbiota from obese individuals would display diminished vascular function compared to germ-free mice receiving microbiota from lean individuals. We transplanted fecal material from obese and lean age-and sex-matched participants with disparate vascular function to germ-free mice. Using Principle Component Analysis, the microbiota of colonized mice separated by donor group along the first principle component, accounting for between 70-93% of the total variability in the dataset. The microbiota of mice receiving transplants from lean individuals was also characterized by increased alpha diversity, as well as increased relative abundance of potentially beneficial bacteria, including Bifidobacterium, Lactobacillus, and Bacteroides ovatis. Endothelium-dependent dilation, aortic pulse wave velocity and glucose tolerance were significantly altered in mice receiving microbiota from the obese donor relative to those receiving microbiota from the lean donor or those remaining germ-free. These data indicate that the obesity-associated human gut microbiota is sufficient to alter the vascular phenotype in germ-free mice in the absence of differences in body weight or dietary manipulation, and provide justification for future clinical trials to test the efficacy of microbiota-targeted therapies in the prevention or treatment of cardiovascular disease.