Korean researchers have uncovered how the gut detects nutrient deficiencies and signals the brain to seek out missing nutrients, revealing the underlying mechanism of gut-brain behavioral regulation.
The Ministry of Science and ICT announced that a research team led by Suh Sung-bae, director of the Center for Microbiome and Body-Brain Physiology at the Institute for Basic Science (IBS), in collaboration with researchers from Seoul National University and Ewha Womans University, identified the operating principles of the gut-brain axis. The findings were published in the world-renowned journal Science on Wednesday.
Until now, it has remained unclear through which neural and hormonal pathways gut-generated signals reach the brain, and how these signals translate into specific food choice behaviors. The team clearly demonstrated how the gut, upon detecting a protein deficiency, alters neural circuits in the brain to prioritize the consumption of essential amino acids.
The research builds on a previous finding that a peptide hormone called "CNMa" is secreted in the guts of protein-deficient fruit flies, leading them to prefer protein-rich foods. The team went further by identifying a new neural circuit beyond the pathway through which the CNMa hormone signal is transmitted to the brain, while also clarifying the principles of nutrient selection.
In new fruit fly experiments, the team confirmed that when intestinal epithelial cells detect a protein deficiency, they send signals to the brain through two channels: a "fast neural signal" and a "slow hormonal signal." First, the gut sends signals to the brain via neural pathways to immediately induce the consumption of essential amino acids. Then, the CNMa hormone is slowly transmitted to the brain through the bloodstream, prompting the continued search for protein.
In this process, the team also confirmed that the CNMa signal both increases protein intake and suppresses the activity of brain neurons that drive carbohydrate consumption. Rather than simply increasing total food intake, this elucidates a "selective feeding behavior" mechanism in which the body preferentially consumes the nutrients it lacks.
This gut-brain axis system was confirmed not only in fruit flies but also in mice, a mammal. Notably, the same behavioral response was maintained even in the absence of "FGF21," previously known as the key hormone in the protein deficiency response, demonstrating the existence of an alternative regulatory system that operates independently of hormones. "This suggests that obesity treatments such as Wegovy and Saxenda may in fact transmit signals not through gut hormones but through direct gut-brain axis neural pathways," the team explained.
The findings, by elucidating the principles and processes of gut-brain regulation of feeding behavior, are expected to be applied to the treatment of obesity, metabolic diseases, and eating disorders in humans. "Most drugs for obesity and appetite control utilize gut hormone signals, but until now, the effects and pathways of naturally secreted gut hormones on the brain and behavior have not been sufficiently studied," said Suh, the IBS center director. "This research, which has revealed the principles of nutrient selection in the gut-brain axis, will serve as an important foundation for future research on the treatment of eating behavior disorders."
