scholarly journals Diammonium Glycyrrhizinate Ameliorates Obesity Through Modulation of Gut Microbiota-Conjugated BAs-FXR Signaling

2021 ◽  
Vol 12 ◽  
Author(s):  
Yun Li ◽  
Huiqin Hou ◽  
Xianglu Wang ◽  
Xin Dai ◽  
Wanru Zhang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intestinal Barrier ◽  
Serum Glucose ◽  
Bile Salt Hydrolase ◽  
Alcoholic Fatty Liver ◽  
Metabolism Disorder ◽  
Glucose And Lipid Metabolism ◽  
Novel Approach ◽  
Treatment Of Obesity ◽  
Host Metabolism

Obesity is a worldwide epidemic metabolic disease. Gut microbiota dysbiosis and bile acids (BAs) metabolism disorder are closely related to obesity. Farnesoid X-activated receptor (FXR), served as a link between gut microbiota and BAs, is involved in maintaining metabolic homeostasis and regulating glucose and lipid metabolism. We previously reported that diammonium glycyrrhizinate (DG) could alter gut microbiota and prevent non-alcoholic fatty liver disease. However, it remains ambiguous how DG affects the gut microbiota to regulate host metabolism. In this present study, 16S rRNA Illumina NovaSeq and metabolomic analysis revealed that DG treatment suppressed microbes associated with bile-salt hydrolase (BSH) activity, which, in turn, increased the levels of taurine-conjugated BAs accompanied by inhibition of ileal FXR-FGF15 signaling. As a result, several obesity-related metabolism were improved, like lower serum glucose and insulin levels, increased insulin sensitivity, few hepatic steatosis and resistance to weight gain. Additionally, decreased level of serum lipopolysaccharide was observed, which contributed to a strengthened intestinal barrier. The effect of DG on weight loss was slightly enhanced in the antibiotics-treated obese mice. Collectively, the efficacy of DG in the treatment of obesity might depend on gut microbiota-conjugated BAs-FXR axis. Hence, it will provide a potential novel approach for the treatment of obesity.

scholarly journals Insights into the Impact of Microbiota in the Treatment of NAFLD/NASH and Its Potential as a Biomarker for Prognosis and Diagnosis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 145
Author(s):  
Julio Plaza-Díaz ◽  
Patricio Solis-Urra ◽  
Jerónimo Aragón-Vela ◽  
Fernando Rodríguez-Rodríguez ◽  
Jorge Olivares-Arancibia ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Liver Steatosis ◽  
Intestinal Barrier ◽  
Fecal Microbiota ◽  
Current Treatment ◽  
Immune Defense ◽  
Alcoholic Fatty Liver ◽  
The Impact

Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation).

scholarly journals Glucosamine Ameliorates Symptoms of High-Fat Diet-Fed Mice by Reversing Imbalanced Gut Microbiota

2021 ◽  
Vol 12 ◽  
Author(s):  
Xubing Yuan ◽  
Junping Zheng ◽  
Lishi Ren ◽  
Siming Jiao ◽  
Cui Feng ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Fat Diet ◽  
Inflammatory Responses ◽  
Fasting Blood Glucose ◽  
Intestinal Barrier ◽  
Intestinal Bacteria ◽  
High Fat ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder ◽  
Rdna Sequencing

Glucosamine (GlcN) is used as a supplement for arthritis and joint pain and has been proved to have effects on inflammation, cancer, and cardiovascular diseases. However, there are limited studies on the regulatory mechanism of GlcN against glucose and lipid metabolism disorder. In this study, we treated high-fat diet (HFD)-induced diabetic mice with GlcN (1 mg/ml, in drinking water) for five months. The results show that GlcN significantly reduced the fasting blood glucose of HFD-fed mice and improved glucose tolerance. The feces of intestinal contents in mice were analyzed using 16s rDNA sequencing. It was indicated that GlcN reversed the imbalanced gut microbiota in HFD-fed mice. Based on the PICRUSt assay, the signaling pathways of glucolipid metabolism and biosynthesis were changed in mice with HFD feeding. By quantitative real-time PCR (qPCR) and hematoxylin and eosin (H&E) staining, it was demonstrated that GlcN not only inhibited the inflammatory responses of colon and white adipose tissues, but also improved the intestinal barrier damage of HFD-fed mice. Finally, the correlation analysis suggests the most significantly changed intestinal bacteria were positively or negatively related to the occurrence of inflammation in the colon and fat tissues of HFD-fed mice. In summary, our studies provide a theoretical basis for the potential application of GlcN to glucolipid metabolism disorder through the regulation of gut microbiota.

scholarly journals The Role of Gut Microbiota in Intestinal Inflammation with Respect to Diet and Extrinsic Stressors

2019 ◽  
Vol 7 (8) ◽  
pp. 271 ◽  
Author(s):  
Stefani Lobionda ◽  
Panida Sittipo ◽  
Hyog Young Kwon ◽  
Yun Kyung Lee
Keyword(s):  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Environmental Stressors ◽  
Intestinal Barrier Function ◽  
Symbiotic Relationship ◽  
Inflammatory Bowel ◽  
Host Metabolism ◽  
The Relationship

The gut microbiota maintains a symbiotic relationship with the host and regulates several important functions including host metabolism, immunity, and intestinal barrier function. Intestinal inflammation and inflammatory bowel disease (IBD) are commonly associated with dysbiosis of the gut microbiota. Alterations in the gut microbiota and associated changes in metabolites as well as disruptions in the intestinal barrier are evidence of the relationship between the gut microbiota and intestinal inflammation. Recent studies have found that many factors may alter the gut microbiota, with the effects of diet being commonly-studied. Extrinsic stressors, including environmental stressors, antibiotic exposure, sleep disturbance, physical activity, and psychological stress, may also play important roles in altering the composition of the gut microbiota. Herein, we discuss the roles of the gut microbiota in intestinal inflammation in relation to diet and other extrinsic stressors.

scholarly journals Intestinal Microbiota Protects against MCD Diet-Induced Steatohepatitis

2019 ◽  
Vol 20 (2) ◽  
pp. 308 ◽  
Author(s):  
Kai Schneider ◽  
Antje Mohs ◽  
Konrad Kilic ◽  
Lena Candels ◽  
Carsten Elfers ◽  
...  
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Neutrophil Infiltration ◽  
Microbiota Composition ◽  
Alcoholic Fatty Liver ◽  
Commensal Microbiota ◽  
Intestinal Dysbiosis ◽  
Physiological Relevance

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in western countries, with a continuously rising incidence. Gut-liver communication and microbiota composition have been identified as critical drivers of the NAFLD progression. Hence, it has been shown that microbiota depletion can ameliorate high-fat diet or western-diet induced experimental Non-alcoholic steatohepatitis (NASH). However, its functional implications in the methionine-choline dietary model, remain incompletely understood. Here, we investigated the physiological relevance of gut microbiota in methionine-choline deficient (MCD) diet induced NASH. Experimental liver disease was induced by 8 weeks of MCD feeding in wild-type (WT) mice, either with or without commensal microbiota depletion, by continuous broad-spectrum antibiotic (AB) treatment. MCD diet induced steatohepatitis was accompanied by a reduced gut microbiota diversity, indicating intestinal dysbiosis. MCD treatment prompted macroscopic shortening of the intestine, as well as intestinal villi in histology. However, gut microbiota composition of MCD-treated mice, neither resembled human NASH, nor did it augment the intestinal barrier integrity or intestinal inflammation. In the MCD model, AB treatment resulted in increased steatohepatitis activity, compared to microbiota proficient control mice. This phenotype was driven by pronounced neutrophil infiltration, while AB treatment only slightly increased monocyte-derived macrophages (MoMF) abundance. Our data demonstrated the differential role of gut microbiota, during steatohepatitis development. In the context of MCD induced steatohepatitis, commensal microbiota was found to be hepatoprotective.

scholarly journals Hepatoprotective effects of Cassiae Semen on mice with non-alcoholic fatty liver disease based on gut microbiota

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Hanyan Luo ◽  
Hongwei Wu ◽  
Lixia Wang ◽  
Shuiming Xiao ◽  
Yaqi Lu ◽  
...  
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Intestinal Barrier ◽  
Therapeutic Effects ◽  
Alcoholic Fatty Liver ◽  
Hepatoprotective Effects ◽  
Underlying Mechanisms ◽  
Alcoholic Fatty Liver Disease

AbstractCassiae Semen (CS), the seeds of Cassia obtusifolia L. and C. tora L, have a long medicinal history in China, with suggestions for it to relieve constipation and exert hepatoprotective effects. However, the underlying mechanisms are still unclear. In this study, mice with high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) were used to study the hepatoprotective effects of CS. The relationship between gut microbiota and hepatoprotective effect mechanisms mediated by CS extracts, the total aglycone extracts of CS, rubrofusarin-6-β-gentiobioside, and aurantio-obtusin were examined. Our data indicate that CS extracts and components confer a protective effect by ameliorating lipid accumulation, intestinal barrier damage, liver damage, and inflammation on HFD-induced liver injury. Meanwhile, fecal microbe transplantation exerted the pharmacological effect of CS on HFD-fed mice; however, the efficacy of CS was inhibited or eliminated by antibiotic-induced dysbiosis. In conclusion, the therapeutic effects of CS on NAFLD were closely related to the gut microbiota, suggesting a role for TCM in treating disease.

scholarly journals Microbiota, Fiber, and NAFLD: Is There Any Connection?

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3100
Author(s):  
Alejandra Pérez-Montes de Oca ◽  
María Teresa Julián ◽  
Analía Ramos ◽  
Manel Puig-Domingo ◽  
Nuria Alonso
Keyword(s):  
Weight Loss ◽  
Gut Microbiota ◽  
Fatty Liver Disease ◽  
Pathogenic Bacteria ◽  
Metabolic Diseases ◽  
Intestinal Barrier ◽  
Alcoholic Fatty Liver ◽  
Fiber Consumption ◽  
Insoluble Fiber ◽  
Alcoholic Fatty Liver Disease

Gut microbiota can contribute to the development and progression of non-alcoholic fatty liver disease (NAFLD). In fact, some specific changes of gut microbiota are observed in patients in what is called dysbiota. There has been a lot of investigation by using a variety of interventions, including diet, showing the possibility to modify components of gastrointestinal dysbiota towards healthy and multivariate microbiota to restore physiologic status. One of the main focuses has been dietary fiber (DF), in which most of its variants are prebiotics. The highest effective treatment for NAFLD is, so far, weight loss achieved by caloric restriction. DF supplementation with oligofructose facilitates weight loss, enhances the production of beneficial metabolites, decreases some pathogenic bacteria population by increasing Bifidobacteria, and has effects on intestinal barrier permeability. DF use has been associated with improvement in diverse metabolic diseases, including NAFLD, by modifying gut microbiota. Additionally, it has been shown that a higher insoluble fiber consumption (≥7.5 g/day) revealed improvements in 3 different scores of liver fibrosis. Further research is needed, but given the evidence available, it is reasonable to prescribe its consumption in early stages of NAFLD in order to prevent disease progression.

scholarly journals The Therapeutic Efficacy of Curcumin vs. Metformin in Modulating the Gut Microbiota in NAFLD Rats: A Comparative Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Ruifang Li ◽  
Yurong Yao ◽  
Pengfei Gao ◽  
Shurui Bu
Keyword(s):  
Gut Microbiota ◽  
Therapeutic Efficacy ◽  
Structural Changes ◽  
Intestinal Barrier ◽  
Inflammatory Factors ◽  
Beneficial Bacteria ◽  
Alcoholic Fatty Liver ◽  
Barrier Integrity ◽  
Before And After ◽  
Intestinal Barrier Integrity

Structural disruption of gut microbiota is closely related to the occurrence of non-alcoholic fatty liver disease (NAFLD). Previous research has demonstrated that both curcumin (CUR) and metformin (MET) have a therapeutic effect against NAFLD and play a role in modulating the gut microbiota. However, there is a lack of direct comparison between the two medications in terms of the therapeutic efficacy and the regulatory effect on gut microbiota. In this study, we administered either CUR or MET to rats with high-fat diet (HFD)-induced obesity to observe changes in body parameters, biochemical parameters, liver, and ileum pathology and gut microbiota, and used next generation sequencing and multivariate analysis to evaluate the structural changes of gut microbiota in a NAFLD rat model before and after CUR and MET intervention. It was found that both CUR and MET attenuated hepatic ectopic fat deposition, alleviated inflammatory factors, and improved intestinal barrier integrity in HFD-fed rats. More importantly, CUR and MET reduced the Firmicutes/Bacteroidetes ratio and reverted the composition of the HFD-disrupted gut microbiota. Both CUR and MET treatments effectively modified the gut microbiome, enriched the abundance of beneficial bacteria and reduced opportunistic pathogens in obese rats. The abundance of Butyricicoccus was increased while the abundance of Dorea was decreased in HFD + CUR group. Besides, some beneficial bacteria such as Prevotella were increased in MET-treated animals. Spearman’s correlation analysis showed that Helicobacter, Akkermansia, Desulfovibrio, Romboutsia, Corynebacterium, Lactobacillus, Ruminococcaceae_unclassified, Lachnospiraceae_unclassified, and Clostridiales_unclassified showed significantly positive correlations with TG, TC, LDL-C, GLU, IL-6, IL-1β, and TNF-α, and negative correlations with HDL-C (both p < 0.05). However, Prevotella and Stomatobaculum showed an opposite trend. In summary, CUR and MET showed similar effects in alleviating hepatic steatosis, improving intestinal barrier integrity and modulating gut microbiota in HFD-induced obesity rats, and therefore may prove to be a novel adjunctive therapy for NAFLD.

scholarly journals Fluoride Induced Leaky Gut and Bloom of Erysipelatoclostridium Ramosum Mediate the Exacerbation of Obesity in High-Fat-Diet Fed Mice

2021 ◽  
Author(s):  
Guijie Chen ◽  
Yujia Peng ◽  
Yujie Huang ◽  
Minhao Xie ◽  
Zhuqing Dai ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Fat Diet ◽  
Fecal Microbiota Transplantation ◽  
Intestinal Barrier ◽  
Fecal Microbiota ◽  
Normal Diet ◽  
High Fat ◽  
Strong Relation ◽  
Potential Strategy ◽  
Treatment Of Obesity

Abstract Background: Fluoride, a necessary mineral element for our health, is widely presented in drinking water and foods. The intake of excessive fluoride showed potential risk to human health. A strong relation between fluoride exposure and obesity has been reported. However, the knowledge on the potential mechanisms on fluoride-induced obesity is still limited.Results: In this work, we showed here that fluoride alone did not induce obesity in normal diet fed mice, whereas, it could trigger exacerbation of obesity in high-fat diet (HFD) fed mice. Fluoride impaired intestinal barrier and activated Toll-like receptor 4 (TLR4) signaling to induce obesity, which was further verified in TLR4-/- mice. Furthermore, fluoride could deteriorate the gut microbiota in HFD mice. The fecal microbiota transplantation from fluoride-induced mice was sufficient to induce obesity, while the exacerbation of obesity by fluoride was blocked upon gut microbiota depletion. The fluoride-induced bloom of Erysipelatoclostridium ramosum belonged to Erysipelotrichaceae was responsible for exacerbation of obesity. In addition, a potential strategy for prevention of fluoride-induced obesity was proposed by intervention with polysaccharides from Fuzhuan brick tea.Conclusions: Overall, these results provide the first evidence of a comprehensive cross-talk mechanism between fluoride and obesity in HFD fed mice, which is mediated by gut microbiota and intestinal barrier. E. ramosum was identified as a crucial mediator of fluoride induced obesity, which could be explored as potential target for prevention and treatment of obesity with exciting translational value.

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