Enterogenic metabolomics signatures of depression: what are the possibilities for the future

An increasing number of studies indicate that the microbiota-gut-brain axis is an important pathway involved in the onset and progression of depression. The responses of the organism (or its microorganisms) to external cues cannot be separated from a key intermediate element: their metabolites.
In recent years, with the rapid development of metabolomics, an increasing amount of metabolites has been detected and studied, especially the gut metabolites. Nevertheless, the increasing amount of metabolites described has not been reflected in a better understanding of their functions and metabolic pathways. Moreover, our knowledge of the biological interactions among metabolites is also incomplete, which limits further studies on the connections between the microbial-entero-brain axis and depression.
This paper summarizes the current knowledge on depression-related metabolites and their involvement in the onset and progression of this disease. More importantly, this paper summarized metabolites from the intestine, and defined them as enterogenic metabolites, to further clarify the function of intestinal metabolites and their biochemical cross-talk, providing theoretical support and new research directions for the prevention and treatment of depression.

越来越多的研究表明，微生物群-肠-脑轴（microbiota-gut-brain axis）是参与抑郁症发生与进展的重要通路。机体（或其共生微生物）对外界刺激信号的响应，离不开一类关键中间介质：代谢物（metabolites）。
近年来，随着代谢组学（metabolomics）的快速发展，越来越多的代谢物被检测并开展研究，其中尤以肠道代谢物最为突出。然而，尽管已报道的代谢物数量持续增长，学界对其功能及代谢通路的认知却并未得到相应深化。此外，学界对代谢物间的生物相互作用的认知仍存在不足，这限制了微生物-肠-脑轴与抑郁症之间关联的后续研究。
本文综述了当前关于抑郁症相关代谢物及其在该病发生与进展过程中作用的研究现状。更为重要的是，本文对肠道来源的代谢物进行了系统梳理，并将其定义为肠源性代谢物（enterogenic metabolites），以期进一步阐明肠道代谢物的功能及其生化串扰机制，为抑郁症的预防与治疗提供理论支撑与全新研究方向。