The gut microbiota in cachexia: master regulator of neuro-immune-metabolic cross-talk

Cachexia, also known as wasting syndrome, is a complex metabolic syndrome triggered by cancer and a variety of severe chronic diseases, characterized by skeletal muscle depletion (with or without loss of adipose tissue) and frequently involving multiple systems. Although inflammation plays a pivotal role in its pathogenesis, the traditional inflammation-centric theory remains insufficient to fully account for the systemic pathological alterations in cachexia. In recent years, growing evidence has demonstrated that the gut microbiota interacts with the neuro-immune-metabolic network, leading to adipose tissue atrophy and muscle catabolism, thereby driving the onset and progression of cachexia. This review systematically delineates the alterations in gut microbiota dysbiosis across various etiologies of cachexia and the functional roles of their related metabolites. It further summarizes the mechanisms by which the gut microbiota regulates cachexia through the nervous system and explores its impact on immune homeostasis and systemic metabolic balance. Furthermore, we highlight current research on cachexia treatment and novel therapeutic strategies based on gut microbiota modulation, providing a theoretical foundation and research direction for the precise diagnosis and intervention of cachexia. This review is expected to offer theoretical support for an in-depth understanding of the multidimensional pathophysiology of cachexia and to promote innovation in clinical intervention strategies.