Dataset Information

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 α-diversity of the microbiota between mGluR5^-/- mice and wild-type controls. The levels of all measured cytokines (IL-1β, IL-2, IL-4, IL-6, IL-10, and TNF-α) 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

ACCESS DATA

Publications

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

Similar Datasets

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.

Project description:Environmental factors and host genetics interact to control the gut microbiota, which may have a role in the development of obesity and insulin resistance. TLR2-deficient mice, under germ-free conditions, are protected from diet-induced insulin resistance. It is possible that the presence of gut microbiota could reverse the phenotype of an animal, inducing insulin resistance in an animal genetically determined to have increased insulin sensitivity, such as the TLR2 KO mice. In the present study, we investigated the influence of gut microbiota on metabolic parameters, glucose tolerance, insulin sensitivity, and signaling of TLR2-deficient mice. We investigated the gut microbiota (by metagenomics), the metabolic characteristics, and insulin signaling in TLR2 knockout (KO) mice in a non-germ free facility. Results showed that the loss of TLR2 in conventionalized mice results in a phenotype reminiscent of metabolic syndrome, characterized by differences in the gut microbiota, with a 3-fold increase in Firmicutes and a slight increase in Bacteroidetes compared with controls. These changes in gut microbiota were accompanied by an increase in LPS absorption, subclinical inflammation, insulin resistance, glucose intolerance, and later, obesity. In addition, this sequence of events was reproduced in WT mice by microbiota transplantation and was also reversed by antibiotics. At the molecular level the mechanism was unique, with activation of TLR4 associated with ER stress and JNK activation, but no activation of the IKKβ-IκB-NFκB pathway. Our data also showed that in TLR2 KO mice there was a reduction in regulatory T cell in visceral fat, suggesting that this modulation may also contribute to the insulin resistance of these animals. Our results emphasize the role of microbiota in the complex network of molecular and cellular interactions that link genotype to phenotype and have potential implications for common human disorders involving obesity, diabetes, and even other immunological disorders.

Project description:BackgroundColorectal cancer (CRC) is one of the most common malignant tumors primarily affecting individuals over the age of 50 years. Recent studies have suggested that the dysbiosis of the gut microbiota, a community of microorganisms in the human gut, is closely associated with the occurrence and development of CRC. Additionally, inflammatory factors (IFs) have also been reported to play a significant role in the development of CRC. However, the causal relationships between the gut microbiota, IFs, and CRC remain unclear.MethodsIn this study, we performed Mendelian randomization (MR) analysis using publicly available genome-wide association study (GWAS) data to explore the causal relationship between the gut microbiota, IFs, and CRC. The gut microbiota GWAS data were obtained from the MiBioGen study, while the IFs GWAS data were derived from the comprehensive analysis of three independent cohorts. Causal relationship analysis was conducted using appropriate instrumental variables (IVs) and statistical models.ResultsMR analysis of the gut microbiota and CRC revealed a negative correlation between the Lachnospiraceae species in the gut and CRC risk, while a positive correlation was observed between Porphyromonadaceae species, Lachnospiraceae UCG010 genus, Lachnospira genus, and Sellimonas genus in the gut, and CRC risk. Additionally, we observed a causal relationship between IL-10 and CRC risk. These findings suggest that the dysbiosis of the gut microbiota might be associated with an increased risk of CRC and that specific bacterial groups may play a crucial role in the occurrence and development of CRC.ConclusionUsing MR analysis, this study revealed the causal relationships between the gut microbiota, IFs, and CRC. The negative correlation between the Lachnospiraceae species in the gut and CRC risk, as well as the causal relationship between IL-10 and CRC, provide important clues for the potential roles of gut microbiota regulation and inflammatory factor control in the prevention and treatment of CRC.

Dataset Information

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

Introduction

Methods

Results

Conclusion

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets