METABOLITES OF THE MICROBIOTA AS PSYCHIATRIC BIOMARKERS: SHORT-CHAIN FATTY ACIDS AND TRYPTOPHAN

Justyna Chudy; Łukasz Ćmok; Julia Dobrowolska; Jakub Robert Skalski; Gabriela Daniel; Karolina Halat; Antoni Hajdas; Natalia Kaczmarczyk; Iga Kałka; Julia Szmuc

doi:10.31435/ijitss.1(49).2026.5281

Authors

Justyna Chudy Beskidzkie Centrum Onkologii, Municipal Hospital of John Paul II in Bielsko-Biała, Bielsko-Biała, Poland https://orcid.org/0009-0006-8824-7260
Łukasz Ćmok Beskidzkie Centrum Onkologii, Municipal Hospital of John Paul II in Bielsko-Biała, Bielsko-Biała, Poland https://orcid.org/0009-0009-3414-4743
Julia Dobrowolska Wojewódzki Szpital Specjalistyczny nr 5 im. św. Barbary w Sosnowcu, Sosnowiec, Poland https://orcid.org/0009-0007-9647-2174
Jakub Robert Skalski Szpital Miejski Specjalistyczny im. G. Narutowicza w Krakowie, Kraków, Poland https://orcid.org/0009-0006-5954-096X
Gabriela Daniel Szpital Powiatowy im. Miłosierdzia Bożego w Limanowej, Limanowa, Poland https://orcid.org/0009-0007-5590-8736
Karolina Halat Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie, Kraków, Poland https://orcid.org/0009-0001-2242-5814
Antoni Hajdas Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie, Kraków, Poland https://orcid.org/0009-0005-1836-6312
Natalia Kaczmarczyk The University Hospital (SU) in Krakow, Kraków, Poland https://orcid.org/0009-0000-4386-4333
Iga Kałka Szpital Specjalistyczny im. Stefana Żeromskiego w Krakowie, Kraków, Poland https://orcid.org/0009-0008-1527-4983
Julia Szmuc Szpital Specjalistyczny im. Stefana Żeromskiego w Krakowie, Kraków, Poland https://orcid.org/0009-0005-4403-3044

DOI:

https://doi.org/10.31435/ijitss.1(49).2026.5281

Keywords:

Microbiota-Gut-Brain Axis, Short-Chain Fatty Acids, SCFA, Tryptophan, Kynurenin Pathway, Psychiatric Biomarkers, Neuroinflammation, Major Depressive Disorder, Schizophrenia, Bipolar Disorder, Pharmacomicrobiomics

Abstract

Background: Severe psychiatric and neurodevelopmental disorders, including depression, bipolar disorder, and schizophrenia, remain a growing global health challenge, with diagnosis still largely based on subjective clinical assessment. Increasing evidence highlights the pivotal role of the microbiota–gut–brain axis (MGBA) in their pathophysiology, particularly neuroactive bacterial metabolites such as short-chain fatty acids (SCFA) and tryptophan derivatives (kynurenine and indole pathways).

Aim: This review synthesizes current evidence on the clinical utility, diagnostic accuracy, and mechanistic relevance of SCFA and tryptophan metabolites as objective biomarkers in major psychiatric disorders.

Methods: A structured literature review was conducted, focusing on multi-omics studies, randomized controlled trials, prospective cohorts, and high-quality meta-analyses. Molecular mechanisms involving GPCR and AhR signaling, HDAC inhibition, neuroinflammatory cascades, and blood–brain barrier regulation were examined. Diagnostic performance indicators, including AUC, sensitivity, and specificity, were analyzed.

Results: SCFA and tryptophan metabolites critically regulate neurogenesis, BDNF expression, synaptic plasticity, microglial polarization, and immune homeostasis. Dysbiosis disrupts the balance between neuroprotective and neurotoxic kynurenine metabolites and reduces protective SCFA levels.

Conclusion: Microbiota-derived metabolic signatures represent promising, objective tools for precision psychiatry. Integration of omics technologies with machine learning may enable biomarker-guided diagnosis and personalized therapeutic strategies targeting the gut–brain axis.

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