Disease-Associated Changes in Bile Acid Profiles and Links to Altered Gut Microbiota

2017 ◽  
Vol 35 (3) ◽  
pp. 169-177 ◽  
Author(s):  
Susan A. Joyce ◽  
Cormac G.M. Gahan
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Bile Acids ◽  
Farnesoid X Receptor ◽  
Gastrointestinal Microbiota ◽  
Signalling Molecules ◽  
Disease States ◽  
Irritable Bowel ◽  
Bile Acid Profiles ◽  
Bile Acid Receptors

The gastrointestinal microbiota plays a central role in the host metabolism of bile acids through deconjugation and dehydroxylation reactions, which generate unconjugated free bile acids and secondary bile acids respectively. These microbially generated bile acids are particularly potent signalling molecules that interact with host bile acid receptors (including the farnesoid X receptor, vitamin D receptor and TGR5 receptor) to trigger cellular responses that play essential roles in host lipid metabolism, electrolyte transport and immune regulation. Perturbations of microbial populations in the gut can therefore profoundly alter bile acid profiles in the host to impact upon the digestive and signalling properties of bile acids in the human superorganism. A number of recent studies have clearly demonstrated the occurrence of microbial disturbances allied to alterations in host bile acid profiles that occur across a range of disease states. Intestinal diseases including irritable bowel syndrome, inflammatory bowel disease (IBD), short bowel syndrome and Clostridium difficile infection all exhibit concurrent alterations in the composition of the gut microbiota and changes to host bile acid profiles. Similarly, extraintestinal diseases and syndromes such as asthma and obesity may be linked to aberrant bile acid profiles in the host. Here, we focus upon recent studies that highlight the links between alterations to gut microbial communities and altered bile acid profiles across a range of diseases from asthma to IBD.

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 Role of Bile Acids in Dysbiosis and Treatment of Nonalcoholic Fatty Liver Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Caihua Wang ◽  
Chunpeng Zhu ◽  
Liming Shao ◽  
Jun Ye ◽  
Yimin Shen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Bile Acid Receptors

Nonalcoholic fatty liver disease (NAFLD) is a major health threat around the world and is characterized by dysbiosis. Primary bile acids are synthesized in the liver and converted into secondary bile acids by gut microbiota. Recent studies support the role of bile acids in modulating dysbiosis and NAFLD, while the mechanisms are not well elucidated. Dysbiosis may alter the size and the composition of the bile acid pool, resulting in reduced signaling of bile acid receptors such as farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). These receptors are essential in lipid and glucose metabolism, and impaired bile acid signaling may cause NAFLD. Bile acids also reciprocally regulate the gut microbiota directly via antibacterial activity and indirectly via FXR. Therefore, bile acid signaling is closely linked to dysbiosis and NAFLD. During the past decade, stimulation of bile acid receptors with their agonists has been extensively explored for the treatment of NAFLD in both animal models and clinical trials. Early evidence has suggested the potential of bile acid receptor agonists in NAFLD management, but their long-term safety and effectiveness need further clarification.

scholarly journals Microbiota-induced obesity requires farnesoid X receptor

Gut ◽  
2016 ◽  
Vol 66 (3) ◽  
pp. 429-437 ◽  
Author(s):  
Ava Parséus ◽  
Nina Sommer ◽  
Felix Sommer ◽  
Robert Caesar ◽  
Antonio Molinaro ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Bile Acid ◽  
Gut Microbiota ◽  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Farnesoid X Receptor ◽  
Wild Type ◽  
Bile Acid Profiles

ObjectiveThe gut microbiota has been implicated as an environmental factor that modulates obesity, and recent evidence suggests that microbiota-mediated changes in bile acid profiles and signalling through the bile acid nuclear receptor farnesoid X receptor (FXR) contribute to impaired host metabolism. Here we investigated if the gut microbiota modulates obesity and associated phenotypes through FXR.DesignWe fed germ-free (GF) and conventionally raised (CONV-R) wild-type andFxr−/−mice a high-fat diet (HFD) for 10 weeks. We monitored weight gain and glucose metabolism and analysed the gut microbiota and bile acid composition, beta-cell mass, accumulation of macrophages in adipose tissue, liver steatosis, and expression of target genes in adipose tissue and liver. We also transferred the microbiota of wild-type andFxr-deficient mice to GF wild-type mice.ResultsThe gut microbiota promoted weight gain and hepatic steatosis in an FXR-dependent manner, and the bile acid profiles and composition of faecal microbiota differed betweenFxr−/−and wild-type mice. The obese phenotype in colonised wild-type mice was associated with increased beta-cell mass, increased adipose inflammation, increased steatosis and expression of genes involved in lipid uptake. By transferring the caecal microbiota from HFD-fedFxr−/−and wild-type mice into GF mice, we showed that the obesity phenotype was transferable.ConclusionsOur results indicate that the gut microbiota promotes diet-induced obesity and associated phenotypes through FXR, and that FXR may contribute to increased adiposity by altering the microbiota composition.

scholarly journals Intestinal bile acid receptors are key regulators of glucose homeostasis

2017 ◽  
Vol 76 (3) ◽  
pp. 192-202 ◽  
Author(s):  
Mohamed-Sami Trabelsi ◽  
Sophie Lestavel ◽  
Bart Staels ◽  
Xavier Collet
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Glucose Homeostasis ◽  
Energy Homeostasis ◽  
Acid Metabolism ◽  
Dietary Lipid ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Metabolism Regulation ◽  
Bile Acid Receptors

In addition to their well-known function as dietary lipid detergents, bile acids have emerged as important signalling molecules that regulate energy homeostasis. Recent studies have highlighted that disrupted bile acid metabolism is associated with metabolism disorders such as dyslipidaemia, intestinal chronic inflammatory diseases and obesity. In particular, type 2 diabetes (T2D) is associated with quantitative and qualitative modifications in bile acid metabolism. Bile acids bind and modulate the activity of transmembrane and nuclear receptors (NR). Among these receptors, the G-protein-coupled bile acid receptor 1 (TGR5) and the NR farnesoid X receptor (FXR) are implicated in the regulation of bile acid, lipid, glucose and energy homeostasis. The role of these receptors in the intestine in energy metabolism regulation has been recently highlighted. More precisely, recent studies have shown that FXR is important for glucose homeostasis in particular in metabolic disorders such as T2D and obesity. This review highlights the growing importance of the bile acid receptors TGR5 and FXR in the intestine as key regulators of glucose metabolism and their potential as therapeutic targets.

Fucose Ameliorate Intestinal Inflammation Through Modulating the Crosstalk Between Bile Acids and Gut Microbiota in a Chronic Colitis Murine Model

2020 ◽  
Vol 26 (6) ◽  
pp. 863-873 ◽  
Author(s):  
Jun Ke ◽  
Ying Li ◽  
Chaoqun Han ◽  
Ruohang He ◽  
Rong Lin ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Bile Acids ◽  
Murine Model ◽  
Intestinal Inflammation ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Chronic Colitis ◽  
16S Rna ◽  
Bile Acid Profiles

Abstract Background Recurrent intestinal inflammation is frequently associated with aberrant bile acid profiles and microbial community. Fucose exerts a protective effect on commensal bacteria in the case of intestinal pathogen infection. We speculated that fucose might also have certain impact on the microbial ecosystem under the chronic colitis setting. Methods To validate our hypothesis, multi-omics examination was performed in combination with microbiomics and metabonomics in a chronic dextran sulfate sodium (DSS) murine model in the presence or absence of fucose. The 16S RNA sequencing was carried out to determine the ileum and colon microbiota. Primary and secondary bile acids, together with the respective taurine and glycine conjugates, were quantified through ultraperformance liquid chromatography coupled with mass spectrometry (UPLC-MS). Moreover, enzymes involved in regulating bile acid synthesis were also detected. Finally, an experiment was carried out on the antibiotic-treated mice to examine the role of gut microbiota. Results Administration of exogenous-free fucose markedly alleviated the inflammatory response in colitis mice. In addition, excessive intestinal bile acid accumulated in DSS mice was decreased in the presence of fucose, along with the restoration of the compromised regulation on hepatic bile acid synthesis. Moreover, the shifts in bile acid profiles were linked with the improved gut microbiome dysbiosis. However, the protective effects of fucose were abolished in mice treated with antibiotic cocktail, indicating that microbiota played a pivotal role. Conclusions Findings in this study suggest that fucose ameliorates colitis through restoring the crosstalk between bile acid and gut microbiota.

scholarly journals Gut Microbiota-Bile Acid Crosstalk in Diarrhea-Irritable Bowel Syndrome

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Kai Zhan ◽  
Huan Zheng ◽  
Jianqing Li ◽  
Haomeng Wu ◽  
Shumin Qin ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Bile Acid ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Gastrointestinal Diseases ◽  
Fecal Microbiota ◽  
Farnesoid X Receptor ◽  
Research Progress ◽  
Functional Connections ◽  
Irritable Bowel

The occurrence of diarrhea-predominant irritable bowel syndrome (IBS-D) is the result of multiple factors, and its pathogenesis has not yet been clarified. Emerging evidence indicates abnormal changes in gut microbiota and bile acid (BA) metabolism have a close relationship with IBS-D. Gut microbiota is involved in the secondary BA production via deconjugation, 7α-dehydroxylation, oxidation, epimerization, desulfation, and esterification reactions respectively. Changes in the composition and quantity of gut microbiota have an important impact on the metabolism of BAs, which can lead to the occurrence of gastrointestinal diseases. BAs, synthesized in the hepatocytes, play an important role in maintaining the homeostasis of gut microbiota and the balance of glucose and lipid metabolism. In consideration of the complex biological functional connections among gut microbiota, BAs, and IBS-D, it is urgent to review the latest research progress in this field. In this review, we summarized the alterations of gut microbiota in IBS-D and discussed the mechanistic connections between gut microbiota and BA metabolism in IBS-D, which may be involved in activating two important bile acid receptors, G-protein coupled bile acid receptor 1 (TGR5) and farnesoid X receptor (FXR). We also highlight the strategies of prevention and treatment of IBS-D via regulating gut microbiota-bile acid axis, including probiotics, fecal microbiota transplantation (FMT), cholestyramine, and the cutting-edge technology about bacteria genetic engineering.

scholarly journals Bile Acid Signaling in Neurodegenerative and Neurological Disorders

2020 ◽  
Vol 21 (17) ◽  
pp. 5982
Author(s):  
Stephanie M. Grant ◽  
Sharon DeMorrow
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Neurological Diseases ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Sphingosine 1 Phosphate ◽  
The Central Nervous System ◽  
Membrane Bound ◽  
Bile Acid Receptors ◽  
Cholestatic Diseases

Bile acids are commonly known as digestive agents for lipids. The mechanisms of bile acids in the gastrointestinal track during normal physiological conditions as well as hepatic and cholestatic diseases have been well studied. Bile acids additionally serve as ligands for signaling molecules such as nuclear receptor Farnesoid X receptor and membrane-bound receptors, Takeda G-protein-coupled bile acid receptor and sphingosine-1-phosphate receptor 2. Recent studies have shown that bile acid signaling may also have a prevalent role in the central nervous system. Some bile acids, such as tauroursodeoxycholic acid and ursodeoxycholic acid, have shown neuroprotective potential in experimental animal models and clinical studies of many neurological conditions. Alterations in bile acid metabolism have been discovered as potential biomarkers for prognosis tools as well as the expression of various bile acid receptors in multiple neurological ailments. This review explores the findings of recent studies highlighting bile acid-mediated therapies and bile acid-mediated signaling and the roles they play in neurodegenerative and neurological diseases.

Bile acid treatment and FXR agonism lower postprandial lipemia in mice

2020 ◽  
Vol 318 (4) ◽  
pp. G682-G693 ◽  
Author(s):  
Sarah Farr ◽  
Bogdan Stankovic ◽  
Simon Hoffman ◽  
Hassan Masoudpoor ◽  
Chris Baker ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Postprandial Lipemia ◽  
Dietary Lipid ◽  
Farnesoid X Receptor ◽  
Postprandial Lipid Metabolism ◽  
Glucagon Like Peptide 1 ◽  
Postprandial Lipid ◽  
Bile Acid Receptors ◽  
G Protein Coupled

Postprandial dyslipidemia is a common feature of insulin-resistant states and contributes to increased cardiovascular disease risk. Recently, bile acids have been recognized beyond their emulsification properties as important signaling molecules that promote energy expenditure, improve insulin sensitivity, and lower fasting lipemia. Although bile acid receptors have become novel pharmaceutical targets, their effects on postprandial lipid metabolism remain unclear. Here, we investigated the potential role of bile acids in regulation of postprandial chylomicron production and triglyceride excursion. Healthy C57BL/6 mice were given an intraduodenal infusion of taurocholic acid (TA) under fat-loaded conditions, and circulating lipids were measured. Targeting of bile acid receptors was achieved with GW4064, a synthetic agonist to the farnesoid X receptor (FXR), and deoxycholic acid (DCA), an activator of the Takeda G-protein-coupled receptor 5. TA, GW4064, and DCA treatments all lowered postprandial lipemia. FXR agonism also reduced intestinal triglyceride content and activity of microsomal triglyceride transfer protein, involved in chylomicron assembly. Importantly, TA (but not DCA) effects were largely lost in FXR knockout mice. These bile acid effects are reminiscent of the antidiabetic hormone glucagon-like peptide-1 (GLP-1). Although the GLP-1 receptor agonist exendin-4 retained its ability to acutely lower postprandial lipemia during bile acid sequestration and FXR deficiency, it did raise hepatic expression of the rate-limiting enzyme for bile acid synthesis. Bile acid signaling may be an important mechanism of controlling dietary lipid absorption, and bile acid receptors may constitute novel targets for the treatment of postprandial dyslipidemia. NEW & NOTEWORTHY We present new data suggesting potentially important roles for bile acids in regulation of postprandial lipid metabolism. Specific bile acid species, particularly secondary bile acids, were found to markedly inhibit absorption of dietary lipid and reduce postprandial triglyceride excursion. These effects appear to be mediated via bile acid receptors, farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). Importantly, bile acid signaling may trigger glucagon-like peptide-1 (GLP-1) secretion, which may in turn mediate the marked inhibitory effects on dietary fat absorption.

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.

Crosstalk between Bile Acids and Gut Microbiota and Its Impact on Farnesoid X Receptor Signalling

2017 ◽  
Vol 35 (3) ◽  
pp. 246-250 ◽  
Author(s):  
Annika Wahlström ◽  
Petia Kovatcheva-Datchary ◽  
Marcus Ståhlman ◽  
Fredrik Bäckhed ◽  
Hanns-Ulrich Marschall
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Bile Acids ◽  
Mouse Models ◽  
Acid Composition ◽  
Farnesoid X Receptor ◽  
Special Importance ◽  
Human Gut ◽  
Substantial Impact ◽  
Human Gut Microbiota

Background: The gut microbiota has a substantial impact on health and disease. The human gut microbiota influences the development and progression of metabolic diseases; however, the underlying mechanisms are not fully understood. The nuclear farnesoid X receptor (FXR), which regulates bile acid homeostasis and glucose and lipid metabolism, is activated by primary human and murine bile acids, chenodeoxycholic acid and cholic acid, while rodent specific primary bile acids tauromuricholic acids antagonise FXR activation. The gut microbiota deconjugates and subsequently metabolises primary bile acids into secondary bile acids in the gut and thereby changes FXR activation and signalling. Key Message: Mouse models have been used to study the crosstalk between bile acids and the gut microbiota, but the substantial differences in bile acid composition between humans and mice need to be considered when interpreting data from such studies and for the development of so-called humanised mouse models. Conclusion: It is of special importance to elucidate how a human gut microbiota influences bile acid composition and FXR signalling in colonised mice.

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