The effects of esketamine on the intestinal microenvironment and intestinal microbiota in mice

Abstract

Objective This study aimed to investigate the impact of esketamine on the intestinal flora and microenvironment in mice using mRNA transcriptome sequencing and 16S rRNA sequencing. Methods Ten female mice were randomly assigned to two groups. One group received daily intramuscular injections of sterile water, while the other group received esketamine. After 24 days, the mice were sacrificed, and their intestinal tissues and contents were collected for 16S rRNA sequencing and mRNA transcriptome sequencing. The intergroup differences in the mouse intestinal flora were analyzed. Differentially expressed genes were utilized to construct ceRNA networks and transcription factor regulatory networks to assess the effects of esketamine on the intestinal flora and intestinal tissue genes. Results Esketamine significantly altered the abundance of intestinal microbiota, including Adlercreutzia equolifaciens and Akkermansia muciniphila. Differential expression analysis revealed 301 significantly upregulated genes and 106 significantly downregulated genes. The ceRNA regulatory network consisted of 6 lncRNAs, 44 miRNAs, and 113 mRNAs, while the regulatory factor network included 13 transcription factors and 53 target genes. Gene Ontology enrichment analysis indicated that the differentially expressed genes were primarily associated with immunity, including B-cell activation and humoral immune response mediation. The biological processes in the ceRNA regulatory network primarily involved transport, such as organic anion transport and monocarboxylic acid transport. The functional annotation of target genes in the TF network was mainly related to epithelial cells, including epithelial cell proliferation and regulation. Conclusion Esketamine induces changes in gut microbiota and the intestinal microenvironment, impacting the immune environment and transport modes.

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“…Remarkably, S-ketamine exerts neuroprotective effects via enhancing autophagy and lessening oxidative stress; the mechanism comprises AMPK/mTOR-dependent autophagy and/or the antioxidant system [78]. Amazingly, Sketamine significantly altered the abundance of intestinal microbiota including Adlercreutzia equolifaciens and Akkermansia muciniphila [79]. It has been revealed that the regulation of NFAT signaling by miR-149 might play a role in the tenacious prophylactic effects of Rketamine in inflammation, and that gut microbiota can regulate the gene expression of miRNAs via the gut-brain axis [80].…”