Fecal microbiota transfer from aged mice promotes hallmarks of vascular ageing and metabolic impairments in young mice

Background and Aims: Ageing is a major risk factor for cardiometabolic diseases, referring to a gradual decline in physiological integrity. Ageing is characterized by 12 well-established hallmarks, such as chronic inflammation, telomere attrition and dysbiosis. During ageing, endothelial dysfunction, increased vascular oxidative stress and enhanced vascular inflammation drive vascular ageing, greatly increasing the risks of atherosclerotic cardiovascular diseases. The current study aims to understand the effect of ageing-associated microbial alterations on vascular and metabolic functions.
Methods: Fecal microbiota transplantation (FMT) was performed from aged to young C57BL/6 mice for 6 weeks, after an 1-week antibiotic cocktail administration. Stools from aged mice (>80 weeks old) were freshly collected to prepare microbiota suspension for oral gavage to young mice (8 weeks old). After the FMT protocol, blood glucose measurements were conducted, and arteries were collected for the determination of vascular function by wire myography and for biochemical assays.
Results: Aged-to-young FMT caused glucose intolerance and insulin resistance in young recipient mice. Such FMT also triggered body weight loss in young mice. More importantly, such FMT induced endothelial dysfunction in aortas and mesenteric arteries of young mice, accompanied by increased ROS generation and upregulated expression of inflammation markers in aortas. The AMPK/eNOS axis was suppressed upon aged-to-young FMT, accounting for the impaired endothelial function. Besides, such FMT altered the lipid profiles of the young mice, hinting potential dyslipidemia.
Conclusions: Our results suggested that ageing-associated dysbiosis might promote vascular ageing hallmarks and metabolic impairments in young mice. (This study was supported by the Health and Medical Research Fund [grant number 08190776]. The work described in this paper was also substantially supported by a fellowship award from the Research Grants Council of the Hong Kong Special Administrative Region, China [Project No. CityU PDFS2223-1S01].)