Does loss of bile acid homeostasis make mice melancholy?

Bile is at the center of the traditional medicines of many cultures. For the ancient Greeks and Romans, each of the four macrocosmic elements that comprised the natural world, fire, earth, air, and water, had a specific microcosmic reflection in the four humors from which the body was constructed, yellow bile, black bile, blood, and phlegm. The view that imbalances in these components cause disease dominated Western medical thought for nearly 2000 years. Ayurvedic, or Indian traditional medicine is based on the similar belief that health is dependent on the balance of the three doshas, pitta (bile), kapha (wind), and vata (phlegm), each of which represents two of their five macrocosmic elements. Bile has a much more humble place in current medical thinking. It is generally thought of as a detergent needed for the absorption of lipids and fat-soluble nutrients, as well as a potentially harmful agent responsible for adverse effects in cholestasis and other pathologic situations. This simplistic view was challenged by the recent discovery by three independent groups (1–3) that a member of the nuclear hormone receptor superfamily, farnesoid X receptor (FXR), functions as a specific receptor for a wide variety of bile acids. Since other members of this family include the receptors for steroids and thyroid hormone, this observation suggested that bile acids should be thought of as hormones.