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. 2021 May 10;11:9915. doi: 10.1038/s41598-021-89308-y

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Hypothesis of a novel mechanism based on α-defensin in the CSDS model. Psychological stress reduces α-defensin produced by Paneth cells in the gut and disrupts the homeostasis of intestinal metabolite composition via dysbiosis. These are normalized by α-defensin administration. Thus, disruption of metabolite homeostasis may affect brain function and lead to the development or exacerbation of depression. However, the direct effects on the brain have not been demonstrated, and are shown as dotted lines.