Microbiota Introduced to Germ-Free Rats Restores Vascular Contractility and Blood Pressure

Abstract

Commensal gut microbiota are strongly correlated with host hemodynamic homeostasis but only broadly associated with cardiovascular health. This includes a general correspondence of quantitative and qualitative shifts in intestinal microbial communities found in hypertensive rat models and human patients. However, the mechanisms by which gut microbes contribute to the function of organs important for blood pressure (BP) control remain unanswered. To examine the direct effects of microbiota on BP, we conventionalized germ-free (GF) rats with specific pathogen-free rats for a short-term period of 10 days, which served as a model system to observe the dynamic responses when reconstituting the holobiome. The absence of microbiota in GF rats resulted with relative hypotension compared with their conventionalized counterparts, suggesting an obligatory role of microbiota in BP homeostasis. Hypotension observed in GF rats was accompanied by a marked reduction in vascular contractility. Both BP and vascular contractility were restored by the introduction of microbiota to GF rats, indicating that microbiota could impact BP through a vascular-dependent mechanism. This is further supported by the decrease in actin polymerization in arteries from GF rats. Improved vascular contractility in conventionalized GF rats, as indicated through stabilized actin filaments, was associated with an increase in cofilin phosphorylation. These data indicate that the vascular system senses the presence (or lack of) microbiota to maintain vascular tone via actin polymerization. Overall, these results constitute a fundamental discovery of the essential nature of microbiota in BP regulation.

Ethanol: striking the cardiovascular system by harming the gut microbiota

“…These data suggest that the vascular system senses the presence (or lack) of microbiota to maintain vascular tone. 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).…”

“…To evaluate the direct effects of microbiota on blood pressure during homeostasis, we conventionalized germ-free (GF) rats with specific pathogen-free rats for ten days (107). The absence of microbiota resulted in relative hypotension in GF rats, compared with their conventionalized counterparts, suggesting an obligatory role of microbiota in blood pressure homeostasis.…”

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.…”

Hypertension Editors’ Picks

“… 2 While the primary mode of viral transmission is inhalation of respiratory droplets, the gastrointestinal epithelium is the body site with greatest ACE2 expression. 2 Furthermore, a critical role for gut in COVID-19 pathophysiology is emerging that is potentially relevant for hypertension-COVID-19 comorbidity 2 : (1) ≈30% to 50% COVID-19 of patients manifest gastrointestinal symptoms, often before respiratory symptoms1; (2) infectious severe acute respiratory syndrome coronavirus 2 has been detected in stool, with viral RNA shedding in feces for weeks 3 ; (3) all patients with COVID-19 show altered fecal microbiome and dysbiosis, even those without gastrointestinal symptoms, 4 and some of those bacterial species adversely influence ACE2 4 ; (4) gut mucosa exhibits all components of renin-angiotensin system 2 ; and (5) the intestinal epithelium supports severe acute respiratory syndrome coronavirus 2 replication. 2 These observations led us to hypothesize that increased ACE2 expression in gut epithelium would predispose hypertension patients to COVID-19 infection.…”