Microbiota alteration is associated with the development of stress-induced despair behavior
Open accessAbstract
Depressive disorders often run in families, which, in addition to the genetic component, may point to the microbiome as a causative agent. Here, we employed a combination of behavioral, molecular and computational techniques to test the role of the microbiota in mediating despair behavior. In chronically stressed mice displaying despair behavior, we found that the microbiota composition and the metabolic signature dramatically change. Specifically, we observed reduced Lactobacillus and increased circulating kynurenine levels as the most prominent changes in stressed mice. Restoring intestinal Lactobacillus levels was sufficient to improve the metabolic alterations and behavioral abnormalities. Mechanistically, we identified that Lactobacillus-derived reactive oxygen species may suppress host kynurenine metabolism, by inhibiting the expression of the metabolizing enzyme, IDO1, in the intestine. Moreover, maintaining elevated kynurenine levels during Lactobacillus supplementation diminished the treatment benefits. Collectively, our data provide a mechanistic scenario for how a microbiota player (Lactobacillus) may contribute to regulating metabolism and resilience during stress.
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A correlation was seen between reduction of L. reuteri in mice following chronic stress and an increase in serum kynurenine concentrations, mediated via a proposed mechanism based on bacterial regulation of GI IDO via H2O2 production.
“Moreover, a correlation was seen between the reduction of L. reuteri in mice following chronic stress with an increase in serum kynurenine concentrations, mediated via a proposed mechanism based on bacterial-regulation of GI IDO via H 2 O 2 production (Marin et al., 2017).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Marin et al., 2017
The Results and Discussion (page unavailable) report increased serum kynurenine after chronic stress and propose a pathway involving Lactobacillus-derived H2O2 and intestinal IDO1. But the reported stress-related decline was in Lactobacillus levels, not specifically L. reuteri; L. reuteri was administered as a supplement. The paper also does not establish the proposed pathway as the mediator of the kynurenine increase. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCandidate psychobiotics that beneficially impact host tryptophan metabolites include Bifidobacterium longum subsp. longum 35624 and L. reuteri.
“Candidate psychobiotics that beneficially impact on host tryptophan metabolites include Bifidobacterium longum subsp.longum 35624 (previously B. infantis 35624) (Desbonnet et al., 2008) and L. reuteri (Marin et al., 2017).”
From Gut reactions: Breaking down xenobiotic–microbiome interactions (2019) · cites this paper as Marin et al., 2017
Higher kynurenine concentrations in the brain were correlated with increased depression-like behavior, which was reduced by administration of Lactobacillus.
“In these studies, higher kynurenine concentrations in the brain were correlated with increased depression-like behavior which was reduced by the administration of Lactobacillus [30].”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [30]
Kynurenine synthesis is modulated by Lactobacillus taxa.
“Another Trp metabolite is kynurenine, the synthesis of which is modulated by Lactobacillus taxa (Marin et al., 2017).”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as Marin et al., 2017
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- Authors
- Marin, I. A., Goertz, J. E., Ren, T., Rich, S. S., Onengut-Gumuscu, S., Farber, E., Wu, M., Overall, C. C., Kipnis, J., & Gaultier, A.
- Affiliations
- University of Virginia (US)
- Corresponding author
- Kipnis, Jonathan
- Gaultier, Alban
- Venue
- Scientific Reports
- Published
- 2017-03-07
- Volume
- 7
- Issue
- 1
- Pages
- 43859-43859
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5339726
- OpenAlex
- W2592499668
- Cited by
- 369
- References
- 66
- Citations by year
- 2026: 21 · 2025: 34 · 2024: 52 · 2023: 33 · 2022: 46 · 2021: 49 · 2020: 48 · 2019: 45 · 2018: 28 · 2017: 13
- FWCI
- 14.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Multiple Sclerosis Society (PP1412)
- University of Michigan
- Multiple Sclerosis Society (PP1412)
- National Institute of Mental Health (R21MH108156)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- gut microbiota, chronic stress, depression, Lactobacillus, kynurenine metabolism, IDO1, reactive oxygen species, stress resilience, metabolic signatures, probiotic supplementation
- MeSH terms
- Gastrointestinal Microbiome, Animals, Depressive Disorder, Intestinal Mucosa, Intestines, Kynurenine, Lactobacillus, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Population Dynamics, RNA, Ribosomal, 16S, Stress, Psychological, Sequence Analysis, DNA, Indoleamine-Pyrrole 2,3,-Dioxygenase
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