scholarly journals Armillaria luteo-virens Sacc Ameliorates Dextran Sulfate Sodium Induced Colitis through Modulation of Gut Microbiota and Microbiota-Related Bile Acids

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3926
Author(s):  
Nana Zhang ◽  
Jianlin Liu ◽  
Xinxin Guo ◽  
Shuying Li ◽  
Fengzhong Wang ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Underlying Mechanism ◽  
Nutritional Intervention ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Rrna Gene ◽  
Novel Approach

Armillaria luteo-virens Sacc (ALS) is a rare wild Chinese medicinal and edible basidiomycete. However, its protective effect on intestinal functions and the underlying mechanism is still unknown. This work explored the improvement of dextran sulfate sodium (DSS)-induced colitis by ALS. ALS supplementation markedly improved colitis symptoms, gut barrier integrity, and goblet loss in DSS-treated mice. In addition, ALS inhibited colonic inflammation through the inhibition/activation of the mitogen-activated protein kinases/NF-κB signaling pathway. The 16S rRNA gene-based microbiota analysis revealed that ALS altered the gut microbiota composition, decreasing the richness of Enterobacteriaceae and increasing the abundance of Lactobacillaceae. The bile-acid-targeted metabolomic analysis showed that ALS recovered the microbial bile acid metabolism in the gut, enabling the activation of the farnesoid X receptor signaling by these acids, thus maintaining the intestinal homeostasis. Importantly, broad-spectrum antibiotic treatment reduced the efficacy of ALS-induced protection from colitis. Overall, our findings suggest that ALS may represent a novel approach in the nutritional intervention to prevent colitis.

scholarly journals Resveratrol Attenuates Trimethylamine- N -Oxide (TMAO)-Induced Atherosclerosis by Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut Microbiota

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Ming-liang Chen ◽  
Long Yi ◽  
Yong Zhang ◽  
Xi Zhou ◽  
Li Ran ◽  
...  
Keyword(s):  
Bile Acid ◽  
Growth Factor ◽  
Gut Microbiota ◽  
Fibroblast Growth Factor ◽  
Farnesoid X Receptor ◽  
Fecal Excretion ◽  
Bile Acid Metabolism ◽  
Bile Salt Hydrolase ◽  
Fibroblast Growth ◽  
As Effects

ABSTRACT The gut microbiota is found to be strongly associated with atherosclerosis (AS). Resveratrol (RSV) is a natural phytoalexin with anti-AS effects; however, its mechanisms of action remain unclear. Therefore, we sought to determine whether the anti-AS effects of RSV were related to changes in the gut microbiota. We found that RSV attenuated trimethylamine- N -oxide (TMAO)-induced AS in ApoE −/− mice. Meanwhile, RSV decreased TMAO levels by inhibiting commensal microbial trimethylamine (TMA) production via gut microbiota remodeling in mice. Moreover, RSV increased levels of the genera Lactobacillus and Bifidobacterium , which increased the bile salt hydrolase activity, thereby enhancing bile acid (BA) deconjugation and fecal excretion in C57BL/6J and ApoE −/− mice. This was associated with a decrease in ileal BA content, repression of the enterohepatic farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) axis, and increased cholesterol 7a-hydroxylase (CYP7A1) expression and hepatic BA neosynthesis. An FXR antagonist had the same effect on FGF15 and CYP7A1 expression as RSV, while an FXR agonist abolished RSV-induced alterations in FGF15 and CYP7A1 expression. In mice treated with antibiotics, RSV neither decreased TMAO levels nor increased hepatic BA synthesis. Additionally, RSV-induced inhibition of TMAO-caused AS was also markedly abolished by antibiotics. In conclusion, RSV attenuated TMAO-induced AS by decreasing TMAO levels and increasing hepatic BA neosynthesis via gut microbiota remodeling, and the BA neosynthesis was partially mediated through the enterohepatic FXR-FGF15 axis. IMPORTANCE Recently, trimethylamine- N -oxide (TMAO) has been identified as a novel and independent risk factor for promoting atherosclerosis (AS) partially through inhibiting hepatic bile acid (BA) synthesis. The gut microbiota plays a key role in the pathophysiology of TMAO-induced AS. Resveratrol (RSV) is a natural phytoalexin with prebiotic benefits. A growing body of evidence supports the hypothesis that phenolic phytochemicals with poor bioavailability are possibly acting primarily through remodeling of the gut microbiota. The current study showed that RSV attenuated TMAO-induced AS by decreasing TMAO levels and increasing hepatic BA neosynthesis via gut microbiota remodeling. And RSV-induced hepatic BA neosynthesis was partially mediated through downregulating the enterohepatic farnesoid X receptor-fibroblast growth factor 15 axis. These results offer new insights into the mechanisms responsible for RSV’s anti-AS effects and indicate that the gut microbiota may become an interesting target for pharmacological or dietary interventions to decrease the risk of developing cardiovascular diseases.

scholarly journals Effect of Electroacupuncture in Mice with Dextran Sulfate Sodium-Induced Colitis and the Influence of Gut Microbiota

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Geng-Hao Liu ◽  
Hsuan-Miao Liu ◽  
Yu-Sheng Chen ◽  
Tzung-Yan Lee
Keyword(s):  
Gut Microbiota ◽  
Tight Junctions ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Experimental Colitis ◽  
16S Rrna Gene Sequencing ◽  
Control Group ◽  
Rrna Gene ◽  
Colonic Inflammation ◽  
The Relationship

Background. The relationship between inflammatory bowel disease and gut microbiota is inextricable. Electroacupuncture (EA) can alleviate acute experimental colitis, but the performance of intestinal microorganisms and the mechanism are still not fully understood. We investigated the relationship between the EA and gut microbes and clarified the role of tight junction and adiponectin in the anti-inflammatory effect of EA. Methods. Male C57BL/6 mice were randomized into three groups: normal control, dextran sulfate sodium- (DSS-) induced ulcerative colitis (DSS), and DSS with EA ST36 (DSS + EA). Mice body weight, DAI score, colon length, and histological score were evaluated for colitis severity. Colonic inflammation and tight junctions were demonstrated by the immunohistochemical (IHC) method. Systemic responses were confirmed by plasma cytokines and adiponectin with multiplex immunoassays. Gut microbiome profiling was conducted by 16S rRNA gene sequencing. Results. EA had benefit in relieving both macroscopic and microscopic colonic inflammation. It can reduce disease activity, maintain colon length, and ameliorate histological inflammatory reaction. In IHC stain, EA decreased CD11b, F4/80, TLR4, and MyD88 and preserved claudin-1 and ZO-1 expression. Compared with the control group, the DSS group showed elevated levels of CRP, IFN-γ, TNF-α, and IL-6, but decreased adiponectin. These changes were reversed by EA, accompanied by modulation of the overall structure of gut microbiota. Conclusion. Our findings suggest that EA exerts its therapeutic effect by TLR4 signaling via the MyD88-dependent pathway. EA could increase adiponectin, maintain mucosal tight junctions, and modulate gut microbiota.

scholarly journals Berberine Alleviates Non-alcoholic Steatohepatitis Through Modulating Gut Microbiota Mediated Intestinal FXR Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiangbing Shu ◽  
Meng Li ◽  
Ying Cao ◽  
Chunlin Li ◽  
Wenjun Zhou ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Inflammatory Cells ◽  
Nuclear Factor Κb ◽  
Farnesoid X Receptor ◽  
Mass Spectrometry Analysis ◽  
Bile Acid Metabolism ◽  
Diverse Range ◽  
Spectrometry Analysis ◽  
Alcoholic Steatohepatitis

Berberine is a natural plant alkaloid isolated from a diverse range of genera, it obtains anti-inflammatory, anti-obesity, and hepatoprotective properties, and is a promising agent for non-alcoholic steatohepatitis (NASH). Farnesoid X receptor (FXR) is a bile acid receptor and a drug target for NASH, however, the underlying mechanisms of berberine on regulating FXR are still unknown. In the present study, we feed mice with a 12-week high-fat diet with interval dextran sulfate sodium (0.5% in drinking water) diet to induce NASH, and treat the mice with berberine (100 mg/kg per day) via oral gavage for additional 4 weeks. We demonstrate that administration of berberine alleviates steatosis and infiltration of inflammatory cells in the liver of NASH mice. We apply 16S ribosomal DNA sequencing to screen the structure of gut microbiota, and ultra-performance liquid chromatography-tandem mass spectrometry analysis to determine the bile acid profiles. The results show that berberine modulates gut dysbiosis, and specifically increases the relative abundance of Clostridiales, Lactobacillaceae, and Bacteroidale. Berberine modulated microbiomes are associated with bile acid de-conjugation and transformation, which are consistent with the altered bile acid species (e.g., deoxycholic acid, ursodeoxycholic acid) upon berberine treatment. BA species that respond to berberine treatment are known FXR agonists, thus we performed quantitative Real Time-PCR and western blot to examine the FXR pathway, and find that berberine up-regulates intestinal FXR and fibroblast growth factor 15 (FGF15) expression, and the secretion of FGF15 further inhibits lipogenesis and nuclear factor-κB activation in the liver. Whereas the beneficial effects of berberine are blunted in FXR knockout mice. Our results reveal that berberine alleviates NASH by modulating the interplay of gut microbiota and bile acid metabolism, as well as the subsequent intestinal FXR activation.

scholarly journals Alleviation of Cholesterol Gallstones by Lactobacillus Targeting the Gut Microbiota Depends on Global Farnesoid X Receptor-Mediated Bile Acid Metabolism

2020 ◽  
Author(s):  
Xinjian Wan ◽  
Xin Ye ◽  
Qian Zhuang ◽  
Zhixia Dong ◽  
Xiaoxin Wang ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Bile Acid ◽  
Gut Microbiota ◽  
Lactobacillus Reuteri ◽  
Cholesterol Gallstone ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Protective Effects ◽  
Lithogenic Diet ◽  
Cytochrome P450 Family

Abstract Background Cholesterol gallstone (CGS) disease is characterized by an imbalance in bile acid (BA) metabolism and is closely associated with gut microbiota disorders. However, the role and mechanism by which probiotics targeting the gut microbiota attenuate CGS are still unknown. In this study, Lactobacillus reuteri CGMCC 17942 (LR) and L. plantarum CGMCC 14407 (LP) were individually administered to lithogenic diet (LD)-fed mice at a dosage of 109 CFU/day for 8 weeks. Results Both Lactobacillus strains significantly reduced LD-induced gallstones, hepatic steatosis, and hyperlipidemia. These strains modulated serum BA profiles, with significantly decreased conjugated primary BA taurine-β-muricholic acid (T-β-MCA), an FXR antagonist. At the molecular level, LR and LP increased Farnesoid X Receptor (FXR) expression in the liver but not in the ileum, increased the levels of ileum and liver fibroblast growth factor 15 (FGF15) and liver FGFR4, small heterodimer partner (SHP), and subsequently reduced cholesterol 7α-hydroxylase (CYP7A1) and cytochrome P450 family 7 subfamily B polypeptide 1 (CYP7B1) to inhibit BA synthesis in the liver. At the same time, the two strains enhanced BA transport by increasing the levels of multidrug-resistance-associated protein homologs (MRP) 3/4, multidrug-resistance-associated protein homologs (MRP) 3/4, hepatic multidrug resistance protein (MDR2) and bile salt export pump (BSEP) mRNA in the liver. In addition, both LR and LP reduced LD-associated gut microbiota dysbiosis. LR increased the relative abundance of Muribaculaceae, while LP increased that of Akkermansia. The changed gut microbiota was significantly negatively correlated with the grade and incidence of gallstones, hyperlipidemia, the level of T-β-MCA in serum, or the gene expression levels of Fxr in liver. Furthermore, the protective effects of the two strains were abolished by a global but not intestinal-specific FXR antagonist. Conclusions Taken together, our results suggested that Lactobacillus might relieve gallstones through FXR-dependent regulation of BA synthesis and transport.

scholarly journals P054 Modulation of the Gut Microbiota-Farnesoid X Receptor Axis Improves Deoxycholic Acid-induced Intestinal Inflammation in Mice

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S161-S161
Author(s):  
M Xu ◽  
Y Shen ◽  
M Cen
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Acid Metabolism ◽  
Deoxycholic Acid ◽  
Intestinal Inflammation ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Gut Dysbiosis ◽  
Rdna Sequencing

Abstract Background Inflammatory bowel disease (IBD) is associated with gut dysbiosis and dysregulation of bile acid metabolism. A high luminal content of deoxycholic acid (DCA) with consumption of a Westernized diet is implicated in the pathogenesis of IBD. The aim of the study is to explore the role of intestinal microbiota and bile acid metabolism in mice with DCA-induced intestinal inflammation. Methods 4-week-old wild-type C57BL mice were fed with AIN-93G (control diet), AIN-93G+0.2% DCA, AIN-93G+0.2% DCA+6 weeks of fexaramine (FXR agonist), or AIN-93G+0.2% DCA+antibiotic cocktail for 24 weeks. Histopathology, Western blotting, and qPCR were performed on the intestinal tissue. Fecal microbiota was analyzed by 16S rDNA sequencing. Fecal bile acid and short-chain fatty acid (SCFA) levels were analyzed by chromatography. Results Gut dysbiosis and enlarged bile acid pool were observed in DCA-treated mice, accompanied by a lower farnesoid X receptor (FXR) activity in the intestine. Administration of fexaramine mitigated DCA-induced intestinal injury, restored intestinal FXR activity, activated fibroblast growth factor 15, and normalized bile acid metabolism. Furthermore, fexaramine administration increased the abundance of SCFA-producing bacteria. Depletion of the commensal microbiota with antibiotics decreased the diversity of the intestinal microbiota, attenuated bile acid synthesis, and reduced intestinal inflammation induced by DCA. Conclusion DCA induced-intestinal inflammation is associated with alterations of gut microbiota and bile acid profiles. Interventions targeting the gut microbiota-FXR signaling pathway may reduce DCA-induced intestinal disease.

scholarly journals Gut Dysbiosis and Abnormal Bile Acid Metabolism in Colitis-Associated Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Li Liu ◽  
Min Yang ◽  
Wenxiao Dong ◽  
Tianyu Liu ◽  
Xueli Song ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Bile Acids ◽  
Acid Metabolism ◽  
Farnesoid X Receptor ◽  
Mucosal Barrier ◽  
Bile Acid Metabolism ◽  
Preventive Strategy ◽  
Gut Dysbiosis ◽  
Bile Acid Receptors

Background. Patients with prolonged inflammatory bowel disease (IBD) can develop into colorectal cancer (CRC), also called colitis-associated cancer (CAC). Studies have shown the association between gut dysbiosis, abnormal bile acid metabolism, and inflammation process. Here, we aimed to investigate these two factors in the CAC model. Methods. C57BL/6 mice were randomly allocated to two groups: azoxymethane/dextran sodium sulfate (AOM/DSS) and control. The AOM/DSS group received AOM injection followed by DSS drinking water. Intestinal inflammation, mucosal barrier, and bile acid receptors were determined by real-time PCR and immunohistochemistry. Fecal microbiome and bile acids were detected via 16S rRNA sequencing and liquid chromatography-mass spectrometry. Results. The AOM/DSS group exhibited severe mucosal barrier impairment, inflammatory response, and tumor formation. In the CAC model, the richness and biodiversity of gut microbiota were decreased, along with significant alteration of composition. The abundance of pathogens was increased, while the short-chain fatty acids producing bacteria were reduced. Interestingly, Clostridium XlV and Lactobacillus, which might be involved in the bile acid deconjugation, transformation, and desulfation, were significantly decreased. Accordingly, fecal bile acids were decreased, accompanied by reduced transformation of primary to secondary bile acids. Given bile acid receptors, the ileum farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) axis was downregulated, while Takeda G-protein receptor 5 (TGR5) was overexpressed in colonic tumor tissues. Conclusion. Gut dysbiosis might alter the metabolism of bile acids and promote CAC, which would provide a potential preventive strategy of CAC by regulating gut microbiota and bile acid metabolism.

scholarly journals Temporal Fluctuations of Gut Microbiota and Bile Acid Metabolism in Critically Ill Children

2021 ◽  
Author(s):  
Iain Robert Louis Kean ◽  
Josef Wagner ◽  
Anisha Wijeyesekera ◽  
Marcus de Goffau ◽  
Sarah Thurston ◽  
...  
Keyword(s):  
Bile Acid ◽  
Critical Illness ◽  
Gut Microbiota ◽  
Bile Acids ◽  
Critically Ill ◽  
Critically Ill Children ◽  
Bile Acid Metabolism ◽  
Rrna Gene ◽  
Secondary Bile Acid ◽  
Secondary Bile Acids

Abstract Background: Critical illness frequently requires the use of broad-spectrum antimicrobials to treat life-threatening infection. The resulting impact on microbiome diversity is profound, influencing gastrointestinal fermentation endpoints, host immune response and metabolic activity including the conversion of primary bile acids to secondary bile acids. We previously observed reduced fermentation capacity in the gut microbiota of critically ill children upon hospital admission, but the functional recovery trajectory of the paediatric gut microbiome during critical illness has not been well defined. Here, we longitudinally studied the intestinal microbiome and faecal bile acid profile of critically ill children during hospitalisation in a paediatric intensive care unit (PICU). The composition of the microbiome was determined by sequencing of the 16s rRNA gene, and bile acids were measured from faecal water by liquid chromatography hyphenated to mass spectrometry. Results: In comparison to admission faecal samples, members of Clostridium cluster XIVa and Lachnospiraceae recovered during the late-acute phase (days 8-10) of hospitalisation. Patients with infections had a lower proportion of Lachnospiraceae in their gut microbiota than control microbiota and patients with admitting diagnoses. The proportion of Recovery Associated Bacteria (RAB) was observed to decline with the length of PICU admission. Additionally, the proportions of RAB were reduced in those with systemic infection, respiratory failure, and undergoing surgery. Notably, Clostridioides were positively associated with the secondary bile acid deoxycholic acid, which we hypothesised to driven by secondary bile acid induced sporulation; the ratio of primary to secondary bile acids demonstrated recovery during critical illness. Conclusion: The recovery of secondary bile acids occurs quickly after intervention for critical illness. Bile acid recovery may be induced by the Lachnospiraceae , the composition of which shifts during critical illness. Our data suggest that gut health and early gut microbiota recovery can be assessed by readily quantifiable faecal bile acid profiles.

scholarly journals S-Propargyl-Cysteine Remodels the Gut Microbiota to Alleviate Rheumatoid Arthritis by Regulating Bile Acid Metabolism

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhou Wang ◽  
Yue Yu ◽  
Junyi Liao ◽  
Wei Hu ◽  
Xiqing Bian ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bile Acid ◽  
Gut Microbiota ◽  
Acid Metabolism ◽  
Amplicon Sequencing ◽  
Bile Acid Metabolism ◽  
Bile Salt Hydrolase ◽  
Rrna Gene ◽  
Inflammatory Status ◽  
Anti Inflammatory

BackgroundRheumatoid arthritis (RA) is a long-term autoimmune disorder characterized by chronic inflammation that results in swollen and painful joints and even cartilage and bone damage. The gut microbiota, a novel anti-inflammatory target, is considered an important environmental factor in the development of RA. S-propargyl-cysteine (SPRC), an amino acid analogue, exerts anti-inflammatory, cardioprotective effects, and neuroprotective effects on various diseases. In recent studies, an SPRC treatment exerted anti-inflammatory effects on RA. Meanwhile, gut microbiome dysbiosis in individuals with RA has also been reported by many researchers. However, the relationship between SPRC and gut microbiota in individuals with RA remains unclear.MethodsThirty male Sprague-Dawley (SD) rats were randomly divided into three groups of 10 each, including the Control, Model, and SPRC groups. Adjuvant-induced arthritis (AIA) rats in SPRC group were treated with SPRC. Measurement of paw volume and serum tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) levels were applied to evaluate the inflammatory status. Fecal samples were collected on the 14th day and 28th day. Gut microbiota were analyzed using 16S ribosomal RNA (rRNA) gene amplicon sequencing. Untargeted metabolomics on plasma samples was applied to investigate the metabolic changes induced by the altered gut microbiota by using derivatization-UHPLC-Q-TOF/MS.FindingsUsing 16S rRNA amplicon sequencing, we found that SPRC significantly altered the gut microbiota structure in AIA rats. In particular, Bifidobacterium, a genus of BSH (Bile Salt Hydrolase)-producing microbes, was overrepresented in SPRC-treated AIA rats. Additionally, a subsequent metabolomics analysis indicated that bile acid metabolism was also altered by SPRC treatment. Interestingly, glycochenodeoxycholic acid (GCDCA) and glycocholic acid (GCA), which are formed with the participation of BSH-producing microbes in the intestine, were identified as crucial biomarkers responding to SPRC treatment with significantly lowered levels.InterpretationA mechanistic link between the gut microbiota and plasma metabolites was revealed in this study, which provides insights into the mechanism of SPRC treatment for RA from the perspective of the gut microbiota.

scholarly journals Ge-Gen-Jiao-Tai-Wan Affects Type 2 Diabetic Rats by Regulating Gut Microbiota and Primary Bile Acids

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Han Chen ◽  
Ye Yao ◽  
Wenbo Wang ◽  
Dongsheng Wang
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Bile Acids ◽  
Intestinal Flora ◽  
Diabetic Rats ◽  
Farnesoid X Receptor ◽  
Rrna Gene ◽  
Fecal Transplant ◽  
Type 2 Diabetic

The Ge-Gen-Jiao-Tai-Wan (GGJTW) formula has been used to treat type 2 diabetes mellitus (T2DM) in China for a long time. Our previous study has proved that GGJTW could alleviate the type 2 diabetic symptoms, but the underlying mechanisms are still unclear. This study aimed to investigate the changes in gut microbiota and primary bile acids (PBAs) to determine the potential mechanisms of GGJTW in treating T2DM.The fecal transplant method and pseudogerm-free rats were used in our study.The16S rRNA gene sequencing method was used to analyze the changes in the intestinal flora, and PBAs in the colon contents were detected. Finally, the expression of farnesoid X receptor (FXR), G protein-coupled membrane receptor 5 (TGR5), and glucagon-like peptide-1 (GLP-1) was assessed. Following GGJTW treatment, we observed a decrease in blood glucose levels and improvements in glucose tolerance and serum lipid levels. Furthermore, we found that GGJTW could regulate the composition of the gut microbiota and upregulate the diabetic beneficial phylum Firmicutes and bile-acid-related genus Lactobacillus. PBAs in the colon contents were increased in the GGJTW-treated group, accompanied by upregulated expression of the bile acid receptors FXR and TGR5 and increased concentrations of GLP-1. These results indicated that GGJTW could alleviate symptoms of type 2 diabetic rats by regulating the gut microbiota, promoting the production of PBAs, and upregulating the PBA-FXR/TGR5-GLP-1 pathway.

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