Gut microbiota and hormones can switch food priorities

Scientists have found that the gut responds to protein starvation through two coordinated pathways. The first is a fast neural circuit that immediately informs the brain about the absence of amino acids. The second is a slower hormonal pathway that supports the animal’s long-term desire to seek out protein-rich food.

The key player in this system is the peptide hormone CNMa. Studies on fruit flies have shown that when protein is scarce in the diet, specialized intestinal cells begin to produce this hormone in abundance. CNMa first activates enteric neurons, which transmit a signal to the brain via a direct pathway, and then enters the bloodstream, reinforcing the animal’s motivation to seek out protein-rich food.

An important feature of this mechanism is its selectivity. The system not only increases appetite but also changes the hierarchy of needs, as animals lose interest in carbohydrates (sugars) and switch to protein-rich foods. CNMa signals effectively suppress the activity of neurons responsible for sugar recognition (so-called DH44 neurons), thereby adjusting food behavior in favor of the missing nutrient.

The study also revealed the influence of the intestinal microflora on this process. Flies deprived of their natural bacteria exhibited excessive activation of neurons responsible for amino acid search, indicating a link between nutrient availability regulated by the microbiota and behavior.

Experiments on mice have confirmed that this mechanism is evolutionarily conserved — it works in a similar way in mammals. Notably, even in mice deprived of the hormone FGF21 (which was previously considered a key regulator of protein appetite), the response to nutrient deficiency was preserved. This proves that there are additional, previously unknown systems of nutrient recognition in the body.

The data obtained expand the understanding of how the gut-brain axis maintains nutritional balance. Most modern appetite-controlling drugs act on gut hormonal signals, but the mechanisms by which natural gut signals influence neural pathways are still poorly understood.

Scientists believe that discovering how this system works could provide a foundation for new therapeutic strategies for obesity, metabolic diseases, and eating disorders. Understanding how the brain selectively adjusts preferences based on specific deficiencies paves the way for developing treatments that restore natural metabolic balance.