Gut–Brain Signalling in Eating and Obesity: Nature Reviews Gastroenterology & Hepatology | August 2026

Introduction:

Eating behaviour is governed by complex interactions between the gastrointestinal tract and the brain that generate hunger, satiation, and satiety. This review examines how gut-derived mechanical and nutrient signals are transmitted and integrated within the nervous system to regulate food seeking, meal consumption, food preference, and energy balance, with particular emphasis on the vagus nerve.

Why was this study needed?

. Obesity cannot be fully explained by energy intake and expenditure without considering neural regulation of eating behaviour.

. The mechanisms linking gastrointestinal signals to hunger, reward, satiety, and food-related learning are increasingly understood but remain fragmented.

. Chronic high-fat and high-sugar diets can directly disrupt gut–brain communication.

. Understanding these pathways could reveal therapeutic targets beyond conventional appetite-suppressing treatments.

Results:

Eating is conceptualized across three interconnected phases: food seeking, food consumption, and non-prandial activity, with transitions controlled by interoceptive signals reflecting nutritional and energy status. The vagus nerve serves as a major conduit carrying mechanical and chemical information from the gastrointestinal tract to the brain. Specialized vagal sensory neurons encode distinct signals that influence meal size, nutrient preference, reinforcement, and memory. These signals interact with brainstem, hypothalamic, dopaminergic, and hippocampal circuits to coordinate homeostatic and reward-driven eating.

Chronic exposure to high-fat, high-sugar diets can impair this regulatory system through vagal desensitization and structural remodeling, altered neuronal gene expression, and leptin resistance. Consequently, physiological control of eating becomes disrupted, promoting hyperphagia, biased food preferences, and habitual overeating.

Clinical Impact:

The gut–brain axis represents an important therapeutic frontier in obesity. Although GLP-1 receptor agonists effectively reduce appetite and body weight, they might not fully reverse the underlying neural abnormalities driving maladaptive eating. Targeting specific vagal sensory pathways could potentially restore physiological interoceptive control and complement current pharmacological obesity treatments.

Bottom Line:

Disrupted gut–brain communication—particularly impaired vagal signalling—is a key mechanism driving maladaptive eating and obesity, making vagal circuits a promising target for next-generation obesity therapies.