BUTYRATE AS A KEY POSTBIOTIC IN THE MODULATION OF NEUROINFLAMMATION: TOWARD PRECISION THERAPY IN TREATMENT-RESISTANT DEPRESSION AND ANXIETY – A NARRATIVE REVIEW
BUTYRATE AS A KEY POSTBIOTIC IN THE MODULATION OF NEUROINFLAMMATION: TOWARD PRECISION THERAPY IN TREATMENT-RESISTANT DEPRESSION AND ANXIETY – A NARRATIVE REVIEW

Summary/Abstract: Background: The escalating global burden of Treatment-Resistant Depression (TRD) and comorbid anxiety necessitates a fundamental shift in psychiatric therapeutic strategies. Traditional monoaminergic hypotheses often fail to account for the systemic inflammatory nature of affective disorders. Recent evidence identifies chronic, low-grade neuroinflammation – driven by the Microbiota-Gut-Brain (MGB) axis – as a primary mediator of treatment failure and neuronal atrophy. Postbiotics, specifically the short-chain fatty acid (SCFA) butyrate, offer a stable, standardized, and bioavailable alternative to live probiotics.Aim of the study: This review provides a comprehensive synthesis of the molecular mechanisms by which butyrate modulates neuroinflammatory pathways, stabilizes biological barriers, and acts as a potent epigenetic regulator to improve clinical outcomes in TRD.Material and methods: A comprehensive narrative review of 49 high-impact studies published between 2010 and 2025 was conducted using PubMed, Web of Science, and Google Scholar.Results: Preclinical data demonstrate that butyrate serves as a potent Histone Deacetylase (HDAC) inhibitor, promoting the expression of Brain-Derived Neurotrophic Factor (BDNF). Furthermore, butyrate mitigates „leaky gut” by upregulating Tight Junction (TJ) proteins (ZO-1, occludin) via the AMPK/Akt pathways and shifts microglial polarization from a pro-inflammatory (M1) to a neuroprotective (M2) phenotype through FFAR2 signaling.Conclusions: Butyrate represents a cornerstone for the future of precision psychiatry. Integrating metabolic profiling (e.g., CRP, IL-6, and fecal SCFA levels) into clinical protocols may enable targeted postbiotic interventions in patients refractory to conventional pharmacotherapy.

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