Abstract 13403: Vagal Nerve Stimulation Mitigates Aberrant Gut Flora Observed in Guinea Pigs With Pressure Overload

Abstract

Background: Altered gut microbial diversity has been associated with several chronic disease states, including heart failure. The vagus nerve, which innervates the heart and abdominal organs, carries information bi-directionally along the gut/brain axis. We hypothesized that vagal nerve stimulation (VNS) could alter gut microbial flora and correct aberrations observed in fecal samples from heart failure animals. Methods and Results: A stimulating device was implanted on either the left or right vagus prior to creation of pressure overload (PO) by aortic constriction. Animals then received continuous, cycling stimulation or sham treatment, and their heart function was monitored by echocardiography. Left ventricular end systolic and diastolic volumes, stroke volume, and cardiac output were significantly impaired in PO animals compared to baseline. VNS mitigated these effects. Animals that did not improve with VNS (15%) were categorized as non-responders. The bacterial DNA 16s ribosomal RNA gene was amplified from fecal DNA and amplicons sequenced for identification of bacterial genera present. Thirty-seven genera were identified as representing at least 0.1% of the total microbial population. Of these, the presence of 17 was disrupted by induction of PO and attenuated by VNS (six with either left or right VNS, five with right VNS only, and six with left VNS only). Metatranscriptomics analysis was then used to predict functional pathways that may be affected by the changes in diversity indicated by sequencing. Genera that express genes associated with ATP-binding cassette (ABC) transport and amino sugar/nitrogen metabolism were significantly changed by PO and VNS therapy. PO-induced changes were mitigated by left cervical vagus stimulation and exacerbated in samples from animals that did not respond to treatment. Conclusion: These data suggest that VNS may improve heart function, at least in part, by reversing pathogenic changes in gut flora that result from blood pressure overload.