Mechanisms by which the gut microbiota regulates depressive disorder via the tryptophan metabolic pathway.
10.11817/j.issn.1672-7347.2025.250163
- Author:
Jing DU
1
,
2
;
Jiao LI
1
;
Pule LIU
1
;
Yan ZHANG
3
;
Qiangli DONG
1
,
4
;
Ning YANG
1
;
Xinru LIU
5
Author Information
1. Department of Psychological Health, Second Hospital, Lanzhou University, Lanzhou
2. 3110378541@qq.com.
3. Department of Psychiatry, Second Xiangya Hospital, Central South University, Changsha
4. 39162597@qq.com.
5. Second Clinical Medical School, Lanzhou University, Lanzhou 730030, China.
- Publication Type:English Abstract
- Keywords:
depressive disorder;
gut microbiota;
inflammation;
microbiota-gut-brain axis;
tryptophan metabolism
- MeSH:
Tryptophan/metabolism*;
Gastrointestinal Microbiome/physiology*;
Humans;
Depressive Disorder/microbiology*;
Probiotics/therapeutic use*;
Brain/metabolism*;
Kynurenine/metabolism*;
Metabolic Networks and Pathways;
Animals;
Medicine, Chinese Traditional
- From:
Journal of Central South University(Medical Sciences)
2025;50(7):1263-1270
- CountryChina
- Language:Chinese
-
Abstract:
The relationship between gut microbiota and depressive disorder has become a research focus in recent years. Within the microbiota-gut-brain axis, the gut microbiota influences the onset and progression of depressive disorder primarily through the tryptophan metabolic pathway. Tryptophan, an essential amino acid in humans, is subject to dual regulation by intestinal microorganisms, which modulate its metabolic balance via inflammatory stimulation and microbial metabolite production. In depression, excessive activation of the kynurenine branch of tryptophan metabolism leads to the accumulation of proinflammatory and neurotoxic metabolites, thereby exacerbating neuroinflammation in the brain. Intervention studies indicate that the antidepressant-like effects of probiotics and traditional Chinese medicine are associated with remodeling of the gut microbiota, restoration of tryptophan metabolic balance, and alleviation of neuroinflammation. Furthermore, targeted inhibition of kynurenine 3-monooxygenase can mitigate neuroinflammation by regulating microglial activity, thus improving depressive-like behaviors. In summary, the metabolite-inflammation axis represents a central node in the interaction regulation between tryptophan metabolism and the microbiota-gut-brain axis. This provides a theoretical foundation for developing novel therapeutic strategies targeting depression through modulation of gut microbiota-mediated tryptophan metabolism.
