Role of Actinobacteria and Coriobacteriia in the antidepressant effects of ketamine in an inflammation model of depression
Nian-nian Huang, Dongyu Hua, Gaofeng Zhan, Shan Li, B. Zhu, Riyue Jiang, Ling Yang, Jiangjiang Bi, Hui Xu, Kenji Hashimoto, A. Luo, Chun Yang
Pharmacology, Biochemistry and Behavior 2019 DOI: 10.1016/j.pbb.2018.12.001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Mice with lipopolysaccharide (LPS)-induced inflammation model of depression |
| Intervention | Ketamine |
| Dose | 10 mg/kg |
| Measures | Forced swimming test (FST), Shannon index, Simpson index, Chao 1 index, principal coordinates analysis (PCoA), linear discriminant analysis (LDA) coupled with effect size measurements (LEfSe), receiver operating characteristic (ROC) curves |
| Topics | Depression Esketamine Ketamine |
| Key points | Ketamine reduced depressive-like behavior in LPS-treated mice and altered gut microbiota composition. The phylum Actinobacteria and class Coriobacteriia were significantly correlated with immobility time and showed potential as biomarkers for ketamine's antidepressant efficacy. |
Abstract
ABSTRACT Ketamine, an N‐methyl‐d‐aspartic acid receptor (NMDAR) antagonist, elicits rapid‐acting and sustained antidepressant effects in treatment‐resistant depressed patients. Accumulating evidence suggests that gut microbiota via the gut‐brain axis play a role in the pathogenesis of depression, thereby contributing to the antidepressant actions of certain compounds. Here we investigated the role of gut microbiota in the antidepressant effects of ketamine in lipopolysaccharide (LPS)‐induced inflammation model of depression. Ketamine (10 mg/kg) significantly attenuated the increased immobility time in forced swimming test (FST), which was associated with the improvements in &agr;‐diversity, consisting of Shannon, Simpson and Chao 1 indices. In addition to &agr;‐diversity, &bgr;‐diversity, such as principal coordinates analysis (PCoA), and linear discriminant analysis (LDA) coupled with effect size measurements (LEfSe), showed a differential profile after ketamine treatment. Furthermore, a total of 30 bacteria were significantly altered in the LPS + saline treated mice and LPS + ketamine treated mice. Interestingly, two bacteria, including the phylum Actinobacteria and the class Coriobacteriia were significantly correlated with the immobility time of FST. Importantly, the receiver operating characteristic (ROC) curves demonstrated that the phylum Actinobacteria and the class Coriobacteriia were potential biomarker for the antidepressant effects of ketamine in an inflammation model. These findings suggest that antidepressant effects of ketamine might be related to the regulation of abnormal composition of gut microbiota, and that the phylum Actinobacteria and the class Coriobacteriia might be potential biomarkers for ketamine's antidepressant efficacy. HighlightsAbnormal composition of gut microbiota might be involved in the mechanisms of inflammation‐induced depression.Improving gut microbiota composition might contribute to the beneficial effects of ketamine on depression symptoms.Phylum Actinobacteria and the class Coriobacteriia might be potential biomarkers for ketamine's antidepressant efficacy.