Bertollo · Frontiers in neuroscience 2025 · narrative review · n=?

Hypothalamus-pituitary-adrenal and gut-brain axes in biological interaction pathway of the depression.

Cited 127 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review describing biological mechanisms without systematic search methods or primary data.

PubMed 39981404 · doi:10.3389/fnins.2025.1541075 · record verified 2026-08-28

What was done

This is a narrative review summarizing theoretical and biological mechanisms connecting the hypothalamic-pituitary-adrenal (HPA) axis and the gut-brain axis in the development and pathophysiology of depression.

What was found

The abstract reports no primary data, quantitative metrics, or statistical findings. It outlines mechanistic pathways: chronic stress induces HPA axis overactivation and sustained cortisol elevation leading to neuronal damage in the hippocampus and prefrontal cortex, while gut microbiota dysbiosis promotes systemic inflammation, increases intestinal permeability, facilitates endotoxin entry into circulation, triggers neuroinflammation, and disrupts peripheral neurotransmitter synthesis, particularly serotonin.

Why it matters

It highlights how stress-response systems and gastrointestinal microbiota may bidirectionally interact to influence mood disorders, pointing toward potential multi-system biological targets in depression research.

Limits

The abstract describes a non-systematic narrative review providing no primary human experimental data, sample sizes, effect estimates, or structured search criteria. The discussed mechanisms remain largely theoretical or preclinical without clinical trial verification presented.

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