Thyroid Dysfunction as a Component of an Immuno-Metabolic Depression-A Possible Role of Gut Microbiota and a Rationale for Future Studies.

Depression is one of the most prevalent psychiatric disorders worldwide, with a steadily increasing incidence and complex, multifactorial pathophysiology. Beyond classical neurochemical mechanisms, growing evidence points to the role of systemic low-grade inflammation and immuno-metabolic disturbances in its development. Gut microbiota dysbiosis has emerged as a key factor linking metabolic, immune, and neuroendocrine pathways, potentially exacerbating neuroinflammation and contributing to the onset and progression of depressive symptoms. Immune activation, which is a result of gut dysbiosis, may play a crucial role in the pathogenesis of immuno-metabolic depression. Thyroid dysfunction appears to be an important, yet insufficiently understood component of this network. Thyroid hormones play a crucial role in regulating metabolism, immune responses, and central nervous system function. Alterations in thyroid function, even within subclinical ranges, have been associated with mood disturbances and may share common inflammatory and metabolic pathways with depression. Furthermore, emerging data suggest that gut microbiota may influence thyroid hormone metabolism, including deiodinase activity, linking dysbiosis with thyroid axis dysregulation. Despite these insights, the integrated interactions between thyroid function, gut microbiota, metabolic syndrome, and inflammation in depression remain largely unexplored. This review explores current evidence to highlight gaps in existing research and synthesizes current knowledge, aiming to clarify mechanisms underlying immuno-metabolic depression. Understanding these relationships may provide a rationale for redefining depression as an immuno-metabolic disorder and support the development of more integrative therapeutic strategies targeting not only the brain, but also the gut-thyroid axis.