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Analysis of the Gut Microbiota and Inflammatory Factors in mGluR5-Knockout Mice.

ABSTRACT: Introduction:Accumulating evidence indicates that the glutamatergic system plays an important role in the development of depression. Notably, the antidepressant effect of metabotropic glutamate receptor 5 (mGluR5) modulation is inconsistent across studies. Here, we attempted to identify the involvement of the gut microbiota and inflammation in mGluR5-/- mice. Methods:mGluR5-/- mice and their wild-type littermates were used in our study. We used the open field (OF) and elevated plus maze (EPM) tests to assess anxiety-like behaviors, and we used the two-day forced swim test (FST) and tail suspension test (TST) to test despair-like behaviors. 16S rDNA was used to analyze the gut microbiota. Enzyme-linked immunosorbent assays (ELISAs) were used to measure the levels of inflammatory factors. Western blotting was used to detect the levels of various proteins. Results:mGluR5-/- mice had no significant increase or decrease of despair-like behavior in the absence of stress exposure. However, mGluR5-/- mice exhibited despair-like behaviors following stress exposure. No significant changes in other glutamate receptors or representative synaptic proteins were detected in the prefrontal cortex (PFC) or hippocampus of mGluR5-/- mice. Very similar bacterial groups were observed in mGluR5-/- mice and wild-type controls. In addition, there was no significant difference in the ?-diversity of the microbiota between mGluR5-/- mice and wild-type controls. The levels of all measured cytokines (IL-1?, IL-2, IL-4, IL-6, IL-10, and TNF-?) did not change significantly in the PFCs or colons of mGluR5-/- mice. Conclusion:In conclusion, we deduced that mGluR5-/- mice are susceptible to despair-like behavior. The systemic knockout of mGluR5 did not affect the gut microbiota or inflammatory factors in mice.

SUBMITTER: Cai G

PROVIDER: S-EPMC7203659 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Analysis of the Gut Microbiota and Inflammatory Factors in mGluR5-Knockout Mice.

Cai Guohong G Zhu Yuanyuan Y Chen Jing J Zhao Suo S Wang Liying L Wang Mengmeng M Huang Jing J Wu Shengxi S

Frontiers in psychiatry 20200430

<h4>Introduction</h4>Accumulating evidence indicates that the glutamatergic system plays an important role in the development of depression. Notably, the antidepressant effect of metabotropic glutamate receptor 5 (mGluR5) modulation is inconsistent across studies. Here, we attempted to identify the involvement of the gut microbiota and inflammation in mGluR5<sup>-/-</sup> mice.<h4>Methods</h4>mGluR5<sup>-/-</sup> mice and their wild-type littermates were used in our study. We used the open field ...[more]

PMID: 32425829

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Project description:PurposeInulin is a type of fermentable dietary fiber, which is non-digestible, and can improve metabolic function by modulating intestinal microbiota. This study aimed to evaluate the role of inulin in hyperuricemia and microbial composition of the gut microbiota in a mouse model of hyperuricemia established through knockout of Uox (urate oxidase) gene.MethodsKO (Uox-knockout) and WT (wild-type) mice were given inulin or saline by gavage for 7 weeks. The effect of inulin to combat hyperuricemia was determined by assessing the changes in serum UA (uric acid) levels, inflammatory parameters, epithelial barrier integrity, fecal microbiota alterations, and SCFA (short-chain fatty acid) concentrations in KO mice.ResultsInulin supplementation can effectively alleviate hyperuricemia, increase the expressions of ABCG2 in intestine, and downregulate expression and activity of hepatic XOD (xanthine oxidase) in KO mice. It was revealed that the levels of inflammatory cytokines and the LPS (lipopolysaccharide) were remarkably higher in the KO group than those in the WT group, indicating systemic inflammation of hyperuricemic mice, but inulin treatment ameliorated inflammation in KO mice. Besides, inulin treatment repaired the intestinal epithelial barrier as evidenced by increased levels of intestinal TJ (tight junction) proteins [ZO-1 (zonula occludens-1) and occluding] in KO mice. Moreover, serum levels of uremic toxins, including IS (indoxyl sulfate) and PCS (p-cresol sulfate), were reduced in inulin-treated KO mice. Further investigation unveiled that inulin supplementation enhanced microbial diversity and raised the relative abundance of beneficial bacteria, involving SCFAs-producing bacteria (e.g., Akkermansia and Ruminococcus). Additionally, inulin treatment increased the production of gut microbiota-derived SCFAs (acetate, propionate and butyrate concentrations) in KO mice, which was positively correlated with the effectiveness of hyperuricemia relief.ConclusionsOur findings showed that inulin may be a promising therapeutic candidate for the treatment of hyperuricemia. Moreover, alleviation of hyperuricemia by inulin supplementation was, at least, partially conciliated by modulation of gut microbiota and its metabolites.

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Analysis of the Gut Microbiota and Inflammatory Factors in mGluR5-Knockout Mice.

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Analysis of the Gut Microbiota and Inflammatory Factors in mGluR5-Knockout Mice.

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