The vagus nerve, the tenth and longest cranial nerve in the body, innervates numerous structures including the larynx, pharynx, heart, lungs, and gastrointestinal tract. The vagus nerve is composed of thousands of axons that work to provide a vast majority of the autonomic innervation in the body. 39,70 This nerve plays a large role in interoceptive awareness and is often regarded as the body's 'sixth sense.' 12,61,73 Although the function of the vagus nerve is largely parasympathetic, it also provides somatic innervation, mainly to the muscles responsible for swallowing and upper airway function. 6 The vagus nerve comprises A, B, and C fiber types, all of which are characterized by different conduction velocities and stimulation thresholds. 14,39,55,60 This nerve consists of both afferent (80%) and efferent (20%) fibers that provide sensory and motor information to maintain homeostasis in nearly every organ system in mammals. 12,39,43,54,65,70 Given the vagus nerve's wide-ranging anatomic targets and neuromodulatory effects, targeted manipulation of this nerve has a broad range of potential experimental and therapeutic applications. In fact, vagal nerve stimulation (VNS) has been used experimentally to establish the contribution of the vagus nerve to numerous behaviors, including immune function, mood, pain, and memory. 70 Furthermore, there is immense interest in using implantable and noninvasive VNS devices to modulate essential functions within the body. 39 VNS has been shown as an effective therapeutic strategy for diverse disorders, and various forms of VNS are currently FDA-approved for treating refractory epilepsy, depression, migraines, cluster headaches, and obesity. 12,30,51,55,60,70-72 In addition, this technology is currently being explored in a multitude of other disorders, including arthritis, asthma, heart failure, gastroparesis, and inflammatory bowel disease, among many others. 30,54,70 Despite the effectiveness of VNS as a treatment strategy, the richness and complexity of the information transmitted along the vagus nerve raises serious challenges that must be considered before widespread use of VNS. 39 Because the vagus nerve innervates multiple organ systems, it is imperative to examine how using VNS to treat a disorder of one organ system might affect healthy function in another. Numerous studies have been conducted on the safety of VNS in regard to cardiovascular and respiratory function. 6,8,10,30 However, although studies have examined the effects of VNS on gastrointestinal function, 45,46,50 no published study has investigated how VNS might influence gastrointestinal microbial populations. 12 This dearth is surprising, given that the vagus nerve is the direct link between the CNS and gastrointestinal tract, serving as a complex bidirectional line of communication