How neural and hormonal gut-brain communication shapes metabolism and health

Uncovering the science of gut and brain signals: How neural and hormonal pathways shape breakthrough treatments for metabolic, behavioral, and health problems.

review: Interoception and gut-brain communication. Image credit: Shutterstock AI

In a recent review published in a magazine current biologyThe researchers explore the origins, mechanisms, and importance of interoception (sensing and processing internal body conditions) and gut-brain communication in homeostasis, highlighting the neural and hormonal pathways that influence feeding behavior and metabolism. I looked into it.

background

The study of interoception dates back centuries, with early philosophers pondering the mind-body interaction. Scientific inquiry gained momentum during the 19th and 20th centuries, linking mental health and visceral function, and stress and gastrointestinal (GI) responses.

This study highlighted important bidirectional communication between the gut and brain, facilitated by neural, hormonal, and microbial pathways that maintain homeostasis and influence behavior. Despite significant advances, the fundamental mechanisms, particularly in the interactions of spinal afferents, the dorsal vagal complex (DVC), and the enteric nervous system (ENS), remain unclear.

Further research is essential to uncover the detailed processes that underpin gut-brain signaling and its role in health and disease.

The emergence of mutual acceptance in modern science

The term “interoception” was coined in the early 20th century and refers to internal sensory receptors. However, research into interoception gained momentum in the mid-20th century through biofeedback therapy for managing metabolic and psychiatric disorders.

The 21st century has seen significant advances in research on the gut-brain axis, revealing its role in integrating external sensory input and internal physiological states to regulate important functions such as food intake, metabolism, and immune responses. I did. This bidirectional feedback between the brain and body supports homeostasis and is essential for overall health.

Evolutionary origins of gut-brain communication

Gut-brain signaling has deep evolutionary roots across invertebrates and vertebrates. Early bilaterians developed a gut-brain axis, allowing coordinated digestive control of the central nervous system (CNS) via the ENS. Comparative studies have highlighted the conservation of neural and hormonal pathways across species.

For example, experiments that sever the gut-brain connection in flies and mammals have demonstrated that metabolic and behavioral regulation is impaired. Such findings highlight the conserved nature of the gut-brain pathway throughout evolution.

Mechanism of communication from the gut to the brain

neural pathway

The vagus nerve is the main nerve conduit that carries gut signals to the brain. Sensory neurons in the nodose ganglia convey mechanosensory information, such as gastric distension, to the brain. It also detects chemical stimuli such as nutrients and inflammatory signals that affect satiety, hunger, and immune responses. Spinal nerves play complementary roles, especially in glucose sensing and energy balance regulation. However, the interaction between spinal afferent signaling and vagal input remains unclear and requires further study.

hormonal pathway

Gut-derived hormones such as ghrelin glucagonBeta-like peptide-1 (GLP-1) acts on both vagal neurons and the brain. Ghrelin stimulates appetite, while GLP-1 promotes satiety and regulates glucose metabolism. Hormone transmission integrates slower systemic responses and faster neural signals to maintain energy homeostasis. Although these pathways are well characterized, they may have untapped therapeutic potential for metabolic diseases.

Microbial interactions

The gut microbiota produces metabolites such as short-chain fatty acids that influence vagal signaling and immune responses. This dynamic interaction between the microbiome and neural pathways shapes gut-brain communication and influences metabolic and cognitive functions.

Recent findings suggest that microbiota-derived metabolites may modulate higher brain functions such as mood and cognition, potentially opening new avenues of research.

Mechanism of brain-gut communication

The brain influences gut function through neural and hormonal pathways. The parasympathetic vagus nerve regulates digestion via motor neurons, controlling gastric contractions and enzyme secretion. In contrast, sympathetic spinal cord signaling inhibits digestion during stress.

Additionally, the hypothalamic-pituitary-adrenal (HPA) axis coordinates hormonal responses, and cortisol modulates intestinal motility and immune function under stress.

brainstem integration

The dorsal vagal complex (DVC) in the brainstem integrates gut-derived signals and coordinates responses. The DVC is comprised of the nucleus tractus solitarius (NTS), the area posteriorly (AP), and the dorsal motor nucleus of the vagus nerve (DMV), which regulates important functions such as hunger and digestion.

Emerging evidence suggests that GLP-1 receptor-expressing neurons in the DVC play a pivotal role in energy homeostasis, particularly in appetite suppression and weight regulation. The NTS processes and relays sensory input to higher brain areas, and the AP detects circulating signals that influence aversion and food intake.

Impact on health and disease

Disturbances in gut-brain signaling have been implicated in a variety of conditions, including obesity, diabetes, and neuropsychiatric disorders. Changes in the composition of the microbiome, hormonal imbalances, or neurological dysfunction can exacerbate these problems. Understanding these mechanisms offers therapeutic possibilities, as demonstrated by GLP-1-based drugs such as semaglutide, which effectively manage diabetes and obesity.

Furthermore, the influence of gut-brain interactions on neurodegenerative diseases such as Alzheimer's disease requires deeper investigation.

conclusion

In summary, studies of interoception and gut-brain communication highlight the complex bidirectional pathways by which the body and brain maintain homeostasis and regulate important functions such as metabolism, hunger, and immune responses.

Rooted in evolutionary biology, gut-brain signaling operates through neural, hormonal, and microbial interactions and exhibits conservation across species. Advances in understanding mechanisms such as the vagus nerve and hormone signaling have changed the way we treat conditions such as diabetes and obesity. However, gaps remain, particularly in the role of spinal afferents and ENS interactions. Focusing on these unexplored areas may uncover new therapeutic targets for treating metabolic, psychiatric, and neurodegenerative diseases.