Gut-brain communication by distinct sensory neurons differently controls feeding and glucose metabolism

Internal senses of the vagus nerve

Omnivores, including rodents and humans, compose their diets from a wide variety of potential foods. Beyond the guidance of a few basic orosensory biases such as attraction to sweet and avoidance of bitter, they have limited innate dietary knowledge and must learn to prefer foods based on their flavors and postoral effects. This review focuses on postoral nutrient sensing and signaling as an essential part of the reward system that shapes preferences for the associated flavors of foods. We discuss the extensive array of sensors in the gastrointestinal system and the vagal pathways conveying information about ingested nutrients to the brain. Earlier studies of vagal contributions were limited by nonselective methods that could not easily distinguish the contributions of subsets of vagal afferents. Recent advances in technique have generated substantial new details on sugar- and fat-responsive signaling pathways. We explain methods for conditioning flavor preferences and their use in evaluating gut–brain communication. The SGLT1 intestinal sugar sensor is important in sugar conditioning; the critical sensors for fat are less certain, though GPR40 and 120 fatty acid sensors have been implicated. Ongoing work points to particular vagal pathways to brain reward areas. An implication for obesity treatment is that bariatric surgery may alter vagal function.

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Learning of food preferences: mechanisms and implications for obesity & metabolic diseases

Background The gut-brain axis, which mediates bidirectional communication between the gastrointestinal system and central nervous system (CNS), plays a fundamental role in multiple areas of physiology including regulating appetite, metabolism, and gastrointestinal function The biology of the gut-brain axis is central to the efficacy of glucagon-like peptide-1 (GLP-1)-based therapies, which are now leading treatments for type 2 diabetes (T2DM) and obesity This success and research to suggest a much broader role of gut-brain circuits in physiology and disease has led to increasing interest in targeting such circuits to discover new therapeutics However, our current knowledge of this biology is limited, largely because the scientific tools have not been available to enable a detailed mechanistic understanding of gut-brain communication Scope of review In this review, we provide an overview of the current understanding of how sensory information from the gastrointestinal system is communicated to the central nervous system, with an emphasis on circuits involved in regulating feeding and metabolism We then describe how recent technologies are enabling a better understanding of this system at a molecular level and how this information is leading to novel insights into gut-brain communication We also discuss current therapeutic approaches that leverage the gut-brain axis to treat diabetes, obesity, and related disorders and describe potential novel approaches that have been enabled by recent advances in the field Major conclusions The gut-brain axis is intimately involved in regulating glucose homeostasis and appetite, and this system plays a key role in mediating the efficacy of therapeutics that have had a major impact on treating T2DM and obesity Research into the gut-brain axis has historically largely focused on studying individual components in this system, but new technologies are now enabling a better understanding of how signals from these components are orchestrated to regulate metabolism While this work reveals a complexity of signaling even greater than previously appreciated, new insights are already being leveraged to explore fundamentally new approaches to treating metabolic diseases

The gut-brain axis: Identifying new therapeutic approaches for type 2 diabetes, obesity, and related disorders.

The gut microbiota has the capacity to affect host appetite via intestinal satiety pathways, as well as complex feeding behaviors. In this Review, we highlight recent evidence that the gut microbiota can modulate food preference across model organisms. We discuss effects of the gut microbiota on the vagus nerve and brain regions including the hypothalamus, mesolimbic system, and prefrontal cortex, which play key roles in regulating feeding behavior. Crosstalk between commensal bacteria and the central and peripheral nervous systems is associated with alterations in signaling of neurotransmitters and neuropeptides such as dopamine, brain-derived neurotrophic factor (BDNF), and glucagon-like peptide-1 (GLP-1). We further consider areas for future research on mechanisms by which gut microbes may influence feeding behavior involving these neural pathways. Understanding roles for the gut microbiota in feeding regulation will be important for informing therapeutic strategies to treat metabolic and eating disorders.

Dan Xu

Papers

A Vagal-NTS Neural Pathway that Stimulates Feeding.