NN: Fatty Foods Disrupt the Gut–Brain Connection

Chronic consumption of fatty foods triggers a chemical malfunction that breaks the connection between the gut and the brain. According to an international team of scientists, an excess of saturated fats sharply increases serotonin levels in the gut while simultaneously depleting its reserves in the brain — specifically in regions responsible for mood, memory, and appetite control. The findings were published in Nutritional Neuroscience (NN).

About 95% of serotonin is synthesized in the gut, where it regulates food movement and blood flow. The remaining — critically small — portion supports brain function, influencing emotions, learning, and satiety. These two systems maintain constant communication through the “gut–brain axis.” The authors of the review set out to understand how a high-fat diet disrupts this dialogue.

A key role is played by enterochromaffin cells in the intestine. Under the influence of fatty foods, they begin producing excessive amounts of serotonin because the enzymes that initiate this process become more active than usual. At the same time, the function of transporter proteins responsible for clearing excess serotonin becomes impaired. As a result, the gut becomes overloaded with this molecule, and its surplus triggers inflammation and damage to the mucosal lining. The intestinal wall becomes more permeable, allowing compounds that normally should not leave the digestive tract to enter the bloodstream.

Meanwhile, the opposite occurs in the brain. In the hippocampus — a region important for memory and emotional stability — serotonin is rapidly broken down. The reason is the increased activity of the enzyme monoamine oxidase A, which degrades neurotransmitters faster than the brain can use them. As a result, the brain becomes less able to recognize satiety, which triggers overeating and metabolic disturbances.

According to the authors, the main mediator of this cascade of disruptions may be the gut microbiota. Healthy bacteria produce short-chain fatty acids that protect the brain and regulate enzymes involved in serotonin metabolism. Fatty foods are low in fiber, depriving beneficial bacteria of necessary nutrients. Levels of protective acids — particularly acetate and butyrate — fall. This impairs serotonin receptor sensitivity and increases inflammation.

Appetite hormones — leptin and ghrelin — play an additional role. A high-fat diet alters their concentrations and disrupts coordinated interactions with serotonin. Elevated cortisol levels, common in people who regularly consume fatty foods, also accelerate serotonin breakdown, since this hormone activates the enzymes responsible for its degradation.

Ultimately, the researchers emphasize, the body is hit with a “double blow”: the gut becomes inflamed and overloaded with serotonin, while the brain experiences a chronic deficiency. This leads to persistent hunger, weight gain, reduced stress resilience, and emotional disturbances — which in turn fuel further overeating.