AUTHOR=Li Jia-Hao , Liu Jia-Li , Li Xiu-Wen , Liu Yi , Yang Jian-Zheng , Chen Li-Jian , Zhang Kai-Kai , Xie Xiao-Li , Wang Qi 

TITLE=Gut microbiota from sigma-1 receptor knockout mice induces depression-like behaviors and modulates the cAMP/CREB/BDNF signaling pathway

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1143648

DOI=10.3389/fmicb.2023.1143648

ISSN=1664-302X

ABSTRACT=There is increasing evidence suggesting a close association between the Sigma-1 receptor (Sig-1R) and depression. However, the mechanisms through which Sig-1R exerts an antidepressant effect are not fully understood. Recently, research has suggested that the gut microbiota may play a crucial role in the development of depression. This study aimed to investigate whether the gut microbiota is involved in depression-like behaviors in mice lacking the Sigmar1 gene, and to explore the potential mechanisms involved. We found that Sig-1R deficiency led to an increase in depression-like behaviors and significant changes in gut microbiota. Antidepressant-like behaviors were restored after depletion of gut microbiota with antibiotics. The gut microbiota of Sig-1R knockout mice was sufficient to induce an increase in depression-like behaviors, which was confirmed through FMT treatment. These effects may be mediated by a reduction in neurotrophic factors through the cAMP/CREB/BDNF signaling pathway. Our study provides new insights into the mechanisms by which Sig-1R regulates depression and further supports the concept of the gut-brain axis.