Microbiota are critical for vascular physiology: Germ-free status weakens contractility and induces sex-specific vascular remodeling in mice

Abstract

Commensal microbiota within a holobiont contribute to the overall health of the host via mutualistic symbiosis. Disturbances in such symbiosis is prominently correlated with a variety of diseases affecting the modern society of humans including cardiovascular diseases, which are the number one contributors to human mortality. Given that a hallmark of all cardiovascular diseases is changes in vascular function, we hypothesized that depleting microbiota from a holobiont would induce vascular dysfunction. To test this hypothesis, young mice of both sexes raised in germ-free conditions were examined vascular contractility and structure. Here we observed that male and female germ-free mice presented a decrease in contraction of resistance arteries. These changes were more pronounced in germ-free males than in germ-free females mice. Furthermore, there was a distinct change in vascular remodeling between males and females germ-free mice. Resistance arteries from male germ-free mice demonstrated increased vascular stiffness, as shown by the leftward shift in the stress-strain curve and inward hypotrophic remodeling, a characteristic of chronic reduction in blood flow. On the other hand, resistance arteries from germ-free female mice were similar in the stress-strain curves to that of conventionally raised mice, but were distinctly different and showed outward hypertrophic remodeling, a characteristic seen in aging.

Ethanol: striking the cardiovascular system by harming the gut microbiota

“…Overall, these results constitute a fundamental discovery of the essential nature of microbiota in blood pressure regulation (107). Corroborating evidence that microbiota is critical for vascular tone and blood pressure control, male and female GF mice also present a decrease in the contraction of resistance arteries (26). However, these changes are more pronounced in GF males than in GF female mice.…”

“…CVD is a multifactorial disorder influenced by environmental and genetic factors. Adding to the complexity of CVD, growing evidence supports that the gut microbiota and its metabolites contribute to cardiovascular dysfunction (22)(23)(24)(25)(26)(27)(28)(29). In addition, the gut microbiota also contributes to ethanol-induced cellular injury (30)(31)(32)(33)(34).…”

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

“…However, this may slightly limit the translatability of these data to future human recipients as some studies have demonstrated variations to GF physiology including alterations in vascular phenotypes and the development of metabolic dysfunction. [40][41][42] Second, our decision to use a single lean and obese donor in each cohort rather than gut microbiota from a mixed group may also reduce the generalizability of the data. Lastly, important questions exist regarding the amount of time that is required for transplantations to elicit physiological changes, as well the duration before those changes begin to wane.…”

Using a Model of Germ-Free Animals to Study the Impact of Gut Microbiome in Research: A Step by Step Sterility Setting and Management

“…Germ free mice have been extensively used for deciphering some mechanisms linked to diseases, such as Type 2 diabetes mellitus, T2DM [15] behavioral functions at the gut-brain axis and autism [16], cardiovascular diseases [17] and cancer [18]. The use of therapeutics to treat these diseases is also investigated with the use of germ-free colonies and use of a standardized protocol and method would be of interest for future studies.…”