‘Survival of the fittest’ is driven by a species’ constant adaptation to a changing environment, which requires both awareness of environmental demands and the ability to engage in the appropriate actions to address them. While external pressures such as rising temperatures or loss of natural habitat drive long-term evolutionary changes, dynamic interoceptive demands also necessitate rapid shifts in behaviors. For example, fluctuations in metabolic hormones can orient towards or away from foraging and ingestive behaviors [1] and social interactions can be heavily guided by reproductive state [2]. This ability to integrate internal signals to guide relevant actions results from extensive lines of communications between the visceral organs and the central nervous system through various humoral and neural signaling pathways. One critical gut-to-brain pathway centers on the vagus nerve, which serves as a key relay between metabolic signals arising from the abdominal viscera and the caudal brainstem [3]. Mechanoreceptors and chemoreceptors on vagal afferent terminals innervating the gut communicate various within-meal signals (e.g., stomach distension, paracrine and/or endocrine signals) to the brainstem to regulate meal size [4]. Within the brain, visceral gut-derived vagal signaling is communicated via diffuse neural projections from the brainstem to the forebrain, including to various hypothalamic, limbic, and cortical regions that regulate energy balance control more broadly.

In addition to being critical in determining food intake regulatory behaviors, emerging findings reveal that the gut-vagal-brain axis modulates various complex cognitive and behavioral processes. Indeed, gut functions have been intrinsically linked to affective states such as anxiety and depression [5], [6], [7], as well as neural processes that regulate learning and memory [8], [9] and motivation [10]. Connections between the gut and cognitive processes were highlighted in the medical community by 19th Century British physicians, who would commonly refer to the stomach as “the great abdominal brain” and a strong regulator of emotional well-being [11], [12]. Interest in a functional connection between the gut and cognitive function has re-emerged based on several recent basic science findings from humans and mechanistic rodent models. This review will synthesize these recent findings emphasizing the contribution of vagus nerve signaling, particularly that originating from the gastrointestinal (GI) tract, in modulating several neurocognitive domains. Results from the literature included are also considered with regards to the relevance of these phenomena from an evolutionary perspective.