VAI TRÒ CHẤT CHUYỂN HOÁ CỦA HỆ VI SINH TRONG TRẦM CẢM: GÓC NHÌN TRỤC RUỘT–NÃO

Abstract

Background: Depression is a prevalent mental disorder affecting approximately 4% of the global population (around 332 million people) and is strongly associated with suicide (727,000 deaths in 2021). At least 30% of patients do not respond adequately to standard treatments, highlighting the urgent need for novel biomarkers and therapeutic targets. Objective: To synthesize evidence on the role of key gut microbiota–derived metabolites in the pathophysiology of depression from a gut–brain axis perspective, focusing on: (i) short-chain fatty acids (SCFAs, particularly butyrate), (ii) indole derivatives from tryptophan, (iii) the tryptophan–kynurenine pathway, and (iv) bile acids and FXR/TGR5 signaling; and to summarize emerging evidence on microbiota-targeted biomarkers and interventions. Methods: A narrative review with a system-oriented approach, prioritizing literature published between 2016 and 2026. Systematic reviews, meta-analyses, and human studies were emphasized, while experimental studies were included to clarify mechanistic pathways. Results: Depression is associated not only with compositional alterations (dysbiosis) but also with functional metabolic changes in the gut microbiota. SCFAs, particularly butyrate, contribute to gut barrier integrity, immune regulation, hypothalamic–pituitary–adrenal (HPA) axis modulation, and epigenetic mechanisms. Indole derivatives act through AhR/PXR signaling, enhance intestinal barrier function, and modulate immune responses; preclinical data suggest links to neuroinflammation and depressive-like behaviors. Activation of the kynurenine pathway, driven by inflammation, reflects a metabolic shift of tryptophan toward neurotoxic and neuroprotective metabolites associated with depression. Altered bile acid profiles and FXR/TGR5 signaling have been reported in major depressive disorder and are emerging as potential biomarkers. Conclusions: The metabolic function of the gut microbiota represents a plausible mechanistic layer linking the gut, immune system, and brain in depression. However, causal evidence in humans remains limited. Longitudinal studies, metabolite-focused interventional trials, and multi-omics approaches may enable identification of “inflammatory–metabolic” phenotypes to support personalized adjunctive treatments targeting the gut–brain axis.