Evidence and Mechanism of Bile Acid-Mediated Gut-Brain Axis in Anxiety and Depression

Bidirectional communication between the brain and gastrointestinal tract, called the gut-brain axis, is linked with our emotions. Intestinal lipids, hormones, and molecules, such as bile acids (BAs), impact our mood, motivation, and emotions via the gut-brain axis. BAs are synthesized from cholesterol in the liver and serve as a regulator of lipid metabolism and hormonal secretion in the intestine. Human studies have indicated that the alteration of plasma BA levels is associated with depression and anxiety. Several possible mechanisms, such as BA receptor-dependent and receptor-independent mechanisms, have been reported for emotional control. Animal studies have indicated that the deletion of BA receptors shows behavioral abnormalities. BAs regulate gut hormones, glucagon-like peptide-1 secretion, bioactive lipids, oleoylethanolamide, and the immune system function, which influences neural activities. Thus, BAs act as an emotional regulator. This review aims to summarize the following: clinical evidence of BA concentration linked to mental disorders, including depression and anxiety; and animal studies of BA-related signaling correlated with its neurobehavioral effect supporting its mechanism. We will also discuss future research required for further neurobehavioral treatment.