<i>Akkermansia muciniphila</i> restores serotonergic gut vagal signaling and lowers blood pressure in rodent model of gut dysbiosis-induced hypertension

Gut microbiome plays a crucial role in maintaining overall host health including effects on blood pressure, metabolism, and neural signaling. An imbalance in gut microbiota has been linked to hypertension, but specific mechanisms underlying host-microbiota interaction remain poorly understood. Our recent study demonstrated a direct and causative link between hypertension-associated gut dysbiosis and diminished serotonergic vagal signaling from the colon contributing to elevated blood pressure in rodents. However, the role of the specific gut bacteria remains unclear. Using bacterial sequencing and real time PCR, we observed significantly decreased abundance of Akkermansia muciniphila (A. muciniphila), a beneficial human gut commensal, in rodent recipients of fecal microbiota transplant from spontaneously hypertensive rats (SHR). Interestingly, the reduced fecal abundance of A. muciniphila was also observed in a Microbiome in aging Gut and Brain (MiaGB) consortium cohort of hypertensive middle- and older- age adults compared to normotensive controls (~5-fold, p&lt;0.05). This reduction was associated with elevated systolic blood pressure (~10-12mmHg) and diminished serotonergic vagal signaling via 5HT3a receptors (5HT3aRs) (2-fold, p&lt;0.05) in rodents receiving the microbiota transplants from the SHR compared to those transplanted with normotensive controls. Conversely, daily administration of A. muciniphila (10 8 CFU) to SHR via oral gavage for 8 weeks significantly reduced systolic blood pressure (by ~20mmHg, p&lt;0.01), elevated colonic serotonin (by ~20ng/mg tissue, p&lt;0.01), and increased the expression of vagal 5HT3aRs (~50%, p&lt;0.05), with no significant changes in the gut bacterial composition and diversity. This study highlights the potential for leveraging A. muciniphila as new therapeutics for alleviation of gut dysbiosis-associated hypertension via serotonergic vagal signaling from the gut. HL152163; FDOH 22A17; U01AG076928; R01AG071762, R21AG072379, and R21AG082164 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.