Gut Microbiota Dysbiosis In Mice Research Articles

Protective effect and mechanism of Monascus-fermented red yeast rice against colitis caused by Salmonella enterica serotype Typhimurium ATCC 14028.

Red yeast rice (RYR), a traditional Chinese fermented food, has the effect of lowering blood lipid and cholesterol, but little information is available about whether RYR can inhibit pathogenic bacterial infection in vivo. The present study explored the effect of RYR on Salmonella enterica-induced intestinal inflammation and gut microbiota dysbiosis in mice as well as the underlying anti-inflammatory mechanism. Results showed that RYR can alleviate S. enterica infection in vivo and Monascus pigments are the main functional components. The analysis of microbiota, gene expression profile and serological immunology revealed that RYR can regulate the intestinal flora and increase the relative abundance of beneficial bacteria such as Lactobacillus and Akkermansia. Meanwhile, RYR is also found to regulate the expression of pro-inflammatory factors and tight junction-related genes to inhibit the NO and NF-κB-mediated inflammatory response and maintain the integrity of the intestinal barrier. This study provides a new dietary intervention strategy for the prevention of pathogenic bacterial infection.

Sarcodon aspratus polysaccharides ameliorated obesity-induced metabolic disorders and modulated gut microbiota dysbiosis in mice fed a high-fat diet.

Sarcodon aspratus is a popular edible fungus that has commonly been used as a functional food in China and other Asian countries. This study is conducted to examine the potential health benefits of Sarcodon aspratus polysaccharides (SATPs), on obesity and related metabolism disorders. C57BL/6J mice were fed with a high-fat diet (HFD) and supplemented with SATPs (100-400 mg kg-1) for 14 weeks. The results indicated that SATP treatment markedly reduced HFD-induced body weight gain and fat accumulation in a dose-dependent manner. SATPs could improve lipid homeostasis and glucose tolerance in HFD-fed mice. Furthermore, SATP intervention significantly attenuated hepatic steatosis, liver oxidative stress and inflammation. Additionally, we detected the macrophage and mRNA levels of lipogenesis markers in epididymal adipose tissues, and the results revealed that SATPs exerted inhibitory effects on the activation of immune cells and adipocyte differentiation in adipose tissues. High-throughput pyrosequencing of 16S rRNA suggested that SATP intervention was able to down-regulate the Firmicutes-to-Bacteroidetes ratio, and also increase the relative abundance of Lactobacillus, Bacteroides and Akkermansia in mice with HFD challenge. Taken together, SATPs showed ameliorative effects on hepatic steatosis, inflammation and adipocyte differentiation in HFD-fed mice. Notably, SATPs could modulate HFD-induced dysbiosis of gut microbiota. Thus, they might be a potential health supplement or prebiotic in the prevention of obesity and related metabolic disorders.

Correlation Analysis of Intestinal Redox State with the Gut Microbiota Reveals the Positive Intervention of Tea Polyphenols on Hyperlipidemia in High Fat Diet Fed Mice.

Tea polyphenols (TP) possess the ability to regulate dyslipidemia and gut microbiota dysbiosis. However, the underlying mechanism is still elusive. The present study explored the intervention of TP on high fat diet induced metabolic disorders, gut microbiota dysbiosis in mice, and the underlying intestinal mechanism. As a result, TP significantly ameliorated hyperlipidemia, improved the expression levels of hepatic lipid metabolism genes, and modulated gut microbiota. The underlying mechanism was supposed to rely on the maintaining of intestinal redox state by TP. Intestinal redox related indicators were significantly correlated with the distribution of gut microbiota. An unidentified genus of Lachnospiraceae, Bacteroides, Alistipes, and Faecalibaculum were identified as the biomarkers for intestinal redox state. Importantly, different dosages of TP modulated intestinal redox state and gut microbiota in varied patterns, and an overdose intake attenuated the beneficial effects on gut health. Our findings offered novel insights into the mechanism of TP on intestinal homeostasis.

Supplementation of okra seed oil ameliorates ethanol-induced liver injury and modulates gut microbiota dysbiosis in mice.

This aim of this study is to assess the possible effects of dietary okra seed oil (OSO) consumption on attenuation of alcohol-induced liver damage and gut microbiota dysbiosis, and associated mechanisms in mice. Mice were orally administered alcohol alone or in combination with OSO at 400 and 800 mg per kg bw for 8 weeks. OSO caused a strong inhibition of abnormal weight loss and liver fat accumulation in alcohol-administered mice. Malonaldehyde production was also effectively antagonized, and glutathione peroxidase and superoxide dismutase activities were elevated by OSO treatment in ethanol-based mice (p < 0.05). Concentrations of hepatic TNF-α, IL-1 and IL-6 were decreased after OSO treatment when compared with alcohol-treated mice, respectively (p < 0.05). As revealed by 16S rDNA gene sequence analysis, OSO notably reduced the Proteobacteria proportion and enhanced the Bacteroidetes population of alcohol-treated mice, and a significant reduction in Clostridium XlVa and Staphylococcus was observed, revealing that OSO attenuated the alcohol-induced gut dysbiosis. OSO also attenuated lipid metabolic disorder by modulating metabolism of serum free fatty acids in ethanol-based mice, but had no significant difference in cecum total short-chain fatty acids among the tested mice. Amelioration of these parameters and liver injury via H&E staining examination demonstrated that OSO consumption could effectively protect against liver damage and maintain intestinal eubiosis in mice.

Lactobacillus plantarum helps to suppress body weight gain, improve serum lipid profile and ameliorate low-grade inflammation in mice administered with glycerol monolaurate

Glycerol monolaurate (GML) is a naturally occurring surfactant and is widely used as a food emulsifier. New evidence, however, has shown that intake of GML could result in metabolic syndrome as well as gut microbiota dysbiosis in mice. In this study, male C57BL/6J mice fed normal chow diet with or without GML supplementation were administered with Lactobacillus plantarum strains isolated from Chinese sourdough for 6 weeks to investigate the influence of GML and the L. plantarum strains on body weight, serum lipid profiles, inflammatory responses and gut microbiota. The results showed that L. plantarum could attenuate the adverse effects induced by GML, especially the strain L. plantarum ZJUFT17, which showed good performance in suppressing body weight gain, lowering total cholesterol, reducing the serum tumor necrosis factor (TNF)-α level and enhancing the α-diversity of gut microbiota in mice supplemented with GML.

Sulforaphane Normalizes Intestinal Flora and Enhances Gut Barrier in Mice with BBN-Induced Bladder Cancer.

Gut microbiota imbalance, inflammation, and gut barrier deficiency play an important role in carcinogenesis. Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, has been proven to be highly effective in inhibiting cancer. The objective of this study is to investigate the potential roles of the gut microbiota in the inhibition of BBN-induced bladder cancer by SFN. N-butyl-N-(4-hydroxybutyl)-nitrosamine is used to induce bladder cancer in male C57BL/6 mice, with or without SFN for 23 weeks. SFN ameliorates the histological changes characteristic of bladder cancer, resulting in fewer submucosal capillaries. SFN normalizes gut microbiota dysbiosis in mice with BBN-induced bladder cancer with a significant increase in Bacteroides fragilis and Clostridium cluster I. SFN also increases butyric acid levels in the mouse colon, and repairs the injury to the mucosal epithelium of the colon and cecum through the upregulation of the expression of tight junction proteins and GLP2. SFN greatly decreases the release of cytokines (IL-6) and secretory immunoglobulin A in the mice with bladder cancer. These results suggest that SFN protects against chemical-induced bladder cancer through normalizing the composition of gut microbiota and repairing the physiological destruction of the gut barrier, as well as decreasing inflammation and the immune response.

Gut microbiota dysbiosis correlates with a low-dose PCB126-induced dyslipidemia and non-alcoholic fatty liver disease

There is growing evidence that polychlorinated biphenyl 126 (PCB126) not only has adverse effects on host health but also has the ability to shift gut microbiota, which is recently recognized as a crucial factor determining numerous physiological processes. However, the interplay between the gut microbiota and host health remains largely unknown. Herein, adult female C57BL/6 mice were orally exposed to environmentally relevant low-dose of PCB126, at 50 μg/kg body weight once per week for 6 weeks. This study aims to illuminate how PCB126 influences gut microbiota variations and host disorders and to further identify the correlation between the gut microbiota and metabolic markers of host disorders. Obtained results demonstrated that the PCB126 administration induced gut microbiota dysbiosis in mice, with changes both in the gut microbiota constitution and structure. PCB126 administration also simultaneously altered the physiological status of serum and liver, as evaluated by dyslipidemia, liver lipid accumulation and injury, and non-alcoholic fatty liver disease. Importantly, Spearman's correlation analysis suggested that several specific bacterial taxa were positively and significantly related to metabolic markers of the mentioned disorders. Moreover, based on the co-occurrence network map, some of the bacterial taxa may synergistically regulate host physiology. This work provides new insight into the mechanism underlying the interaction between the gut microbiota and host disorders. It is expected that gut microbiota modulation should be another novel way used for the prevention and treatment of PCB126-triggered diseases.

Insights into a Possible Mechanism Underlying the Connection of Carbendazim-Induced Lipid Metabolism Disorder and Gut Microbiota Dysbiosis in Mice.

Carbendazim (CBZ), a systemic, broad-spectrum benzimidazole fungicide, is widely used to control fungal diseases and has been regarded as an endocrine disruptor that causes mammalian toxicity in different target organs. Here, we discovered that chronic administrations of CBZ at 0.2, 1, and 5 mg/kg body weight for 14 weeks not only changed the composition of gut microbiota but also induced significant increases in body, liver, and epididymal fat weight in mice. At the biochemical level, the serum triglyceride (TG) and glucose levels also increased after CBZ exposure. Moreover, the level of serum lipoprotein lipase (LPL), which plays an important role in fatty acid release from TG, was decreased significantly. For gut microbiota, 16S rRNA gene sequencing and real-time qPCR revealed that CBZ exposure significantly perturbed the mice gut microbiome, and gas chromatography found that the production of short-chain fatty acids were altered. Moreover, CBZ exposure increased the absorption of exogenous TG in the mice intestine and inhibited the TG consumption, eventually leading the serum triglyceride to maintain higher levels. The increase of lipid absorption in the intestine direct caused hyperlipidemia and the multi-tissue inflammatory response. In response to the rise of lipid in blood, the body maintains the balance of lipid metabolism in mice by reducing lipid synthesis in the liver and increasing lipid storage in the fat. Chronic CBZ exposure induced the gut microbiota dysbiosis and disturbed lipid metabolism, which promoted the intestinal absorption of excess triglyceride and caused multiple tissue inflammatory responses in mice.

Oral Exposure of Mice to Carbendazim Induces Hepatic Lipid Metabolism Disorder and Gut Microbiota Dysbiosis.

Carbendazim (CBZ) has been considered as an endocrine disruptor that caused mammalian toxicity in different endpoints. Here, we revealed that oral administrations with CBZ at 100 and 500 mg/kg body weight for 28 days induced hepatic lipid metabolism disorder which was characterized by significant increases of hepatic lipid accumulation and triglyceride (TG) levels in mice. The serum cholesterol (TC), high-density lipoprotein, and low-density lipoprotein levels also increased after CBZ exposure. Correspondingly, the relative mRNA levels of some key genes related to lipogenesis and TG synthesis increased significantly both in the liver and fat. Moreover, the increase in serum IL-1β and IL-6 levels by the treatment of CBZ indicated the occurring of inflammation. Furthermore, the levels of bioaccumulation of CBZ in the liver and gut were very low as compared in the feces, indicating that most of CBZ stayed in gastrointestinal tract and interacted with gut microbiota until excreted. At phylum level, the amounts of the Bacteroidetes decreased significantly in the feces after 5 days CBZ exposure. High throughput sequencing of the 16S rRNA gene V3-V4 region revealed a significant reduction in richness and diversity of gut microbiota in the cecum of CBZ-treated mice. UniFrac principal coordinates analysis observed a marked shift of the gut microbiota structure in CBZ-treated mice away from that of the controls. More deeply, operational taxonomic units' analysis identified that a total of 361 gut microbes were significant changed. In CBZ-treated groups, the relative abundance of Firmicutes, Proteobacteria, and Actinobacteria increased and that of Bacteroidetes decreased. Our findings suggested that CBZ could lead hepatic lipid metabolism disorder and gut microbiota dysbiosis in mice.