The microbiota in the gut is a highly active community of microorganisms whose health can influence host physiology. A new pre-clinical study reported that the microbiota composition was altered by chronic mild stress and feeding the affected mice with a specific probiotic species alleviated their depressive behavior.1
To understand whether chronic stress directly affected microbiota, researchers from the Department of Neuroscience at the University of Virginia first induced behavioral despair in mice using a validated protocol known as the unpredictable chronic mild stress (UCMS) model. Once the stress-induced behavioral despair was exhibited, the researchers studied the microbiota composition of the animals. They found that chronic stress disturbed the microbiota homeostasis, in particular by decreasing the Lactobacillus levels.
Next, the researchers fed the stressed mice with the probiotic strain Lactobacillus reuteri (ATCC 23272) while continuing the UCMS protocol for additional 4 weeks. They found that the probiotic supplementation ameliorated the depressive symptoms. Mechanistically, the researchers believed that Lactobacillus reuteri mediated the metabolism of kynurenine, a metabolite of the amino acid tryptophan. Evidence from both animal and human studies has shown that dysregulation in the kynurenine pathway to be linked to depression, psychiatric diseases and neuroinflammation.2 Modulation of kynurenine pathway via probiotic supplementation warrants future research.
The authors indicated that the microbiome can play a causative role in the development and symptomatology of depression in both pre-clinical and clinical models, and the gut microbiota could be a therapeutic target to alleviate depression with appropriate probiotic strains.
The study results were published in the journal Scientific Reports (March 2017).
Why is this clinically important?
- Depression affects nearly 7% of the population in the United States3
- Microbiome composition is disrupted in humans affected by major depressive disorders4
- Supplementation of probiotics may beneficially alter the microbiota of the host and thus confer beneficial effects on the host, including mental health
- Marin IA, Goertz JE, Ren T, et al. Microbiota alteration is associated with the development of stress-induced despair behavior. Sci Rep 2017;7:43859.
- Reus GZ, Jansen K, Titus S, Carvalho AF, Gabbay V, Quevedo J. Kynurenine pathway dysfunction in the pathophysiology and treatment of depression: Evidences from animal and human studies. J Psychiatr Res 2015;68:316-28.
- Kupfer DJ, Frank E, Phillips ML. Major depressive disorder: new clinical, neurobiological, and treatment perspectives. Lancet 2012;379:1045-55.
- Zheng P, Zeng B, Zhou C, et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism. Mol Psychiatry 2016;21:786-96.