We are pleased to announce a new publication in Acta Materia Medica that addresses an important clinical issue: the high incidence of depressive-like behavior among patients suffering from cholestatic liver disease, which significantly impairs their quality of life.
This condition highlights the urgent need for research into the underlying mechanisms linking cholestasis with depression. Our review delves deeply into how neuroendocrine disorders caused by cholestasis contribute to depression through both direct and indirect pathways.
Firstly, we examine how bile acid accumulation in the central nervous system (CNS) during cholestasis damages the blood-brain barrier, triggers neuroinflammation, and leads to neurodegeneration. We underscore the crucial role played by bile acid receptors such as FXR and TGR5 in this process.
Furthermore, we explore how the gut-brain axis plays a significant role in various brain diseases. This review summarizes the indirect effects of bile acids on depression through their impact on gut microbiota composition, gut barrier integrity, and the secretion of gut hormones via this pathway. These mechanisms collectively regulate the development of depressive symptoms.
However, critical questions remain: can bile acids directly enter the CNS? And which specific targets within the gut-brain axis are potential therapeutic targets?
Answering these fundamental questions could pave the way for developing more effective strategies to alleviate depressive symptoms in patients with cholestasis.
