Molecular neurobiologyJan 28, 2025

How Probiotics May Affect Depression Through Stress Response and Tryptophan Breakdown in the Gut-Brain Axis

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 3, 2026

Abstract

Tryptophan metabolism may influence depression through the serotonin and kynurenine pathways.

Depression is characterized by symptoms such as worthlessness, anhedonia, and disturbances in sleep and appetite.
The enzyme tryptophan 5-monooxygenase (TPH) is involved in serotonin production, while indoleamine-2,3-dioxygenase (IDO) is linked to the kynurenine pathway.
IDO activation by proinflammatory cytokines during neuroinflammation may impact neurogenesis, cognition, and the hypothalamic-pituitary-adrenal (HPA) axis.
Changes in gut bacteria and their metabolites, including tryptophan derivatives, may be associated with disturbed gut homeostasis in depression.
The relationship between gut microbiota and mental health is referred to as the gut-brain axis (GBA).
Limited information exists on the effects of probiotics supplementation on depression through IDO and kynurenine pathway metabolites.

Simplified

Depression is one of the most disabling mental disorders worldwide and characterized by symptoms including worthlessness, anhedonia, sleep, and appetite disturbances. Recently, studies have suggested that tryptophan (Trp) metabolism plays a key role in depressed mood through serotonin and kynurenine pathway involving enzyme tryptophan 5-monooxygenase (TPH) and indoleamine-2,3-dioxygenase (IDO) respectively. Moreover, during neuroinflammation, IDO is activated by proinflammatory cytokines and affects neurogenesis, cognition, disturbed hypothalamic-pituitary-adrenal (HPA) axis, and gut homeostasis by altering the gut bacteria and its metabolites like Trp derivatives. Furthermore, over the decades, researchers have focused on understanding communication between the human microbiome, especially gut microbiota, and mental health, called gut-brain-axis (GBA), particularly through Trp metabolism. Supplementation of probiotics in depression has gained attention from researchers and clinicians. However, there is limited information about probiotics supplementation on depression involving enzyme IDO and kynurenine pathway metabolites. This review discussed the potential role of probiotics in depression through the tryptophan/kynurenine pathway.

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How Probiotics May Affect Depression Through Stress Response and Tryptophan Breakdown in the Gut-Brain Axis

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