Bile acids in glucose metabolism in health and disease

Shapiro, Hagit; Kolodziejczyk, Aleksandra A.; Halstuch, Daniel; Elinav, Eran

doi:10.1084/jem.20171965

Cited by 316 publications

(263 citation statements)

References 148 publications

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“…The increased secondary bile acid, deoxycholic acid, in the plasma of RS mice is likely due to increased bacterial action in the colon. Bile acid sequestrants have been shown to produce improvements in glycemic profile in subjects with type 2 diabetes (62). A marker of oxidative stress, glutathione (GSH), plays an important role in detoxifying oxygen radicals and therefore may prevent cellular damage from oxidative stress (63).…”

Section: Discussionmentioning

confidence: 99%

Ingestion of resistant starch by mice markedly increases microbiome‐derived metabolites

et al. 2019

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Recent research has shown significant health benefits deriving from high‐dietary fiber or microbiome‐accessible carbohydrate consumption. Compared with native starch (NS), dietary resistant starch (RS) is a high microbiome‐accessible carbohydrate that significantly alters the gut microbiome. The aim of this study was to determine the systemic metabolic effects of high microbiome‐accessible carbohydrate. Male C57BL/6 mice were divided into 2 groups and fed either NS or RS for 18 wk (n = 20/group). Metabolomic analyses revealed that plasma levels of numerous metabolites were significantly different between the RS‐fed and NS‐fed mice, many of which are microbiome‐derived. Most strikingly, we observed a 22‐fold increase in gut microbiome‐derived tryptophan metabolite indole‐3‐propionate (IPA), which was positively correlated with several gut microbiota, including Allobaculum, Bifidobacterium, and Lachnospiraceae, with Allobaculum having the most consistently increased abundance of all the IPA‐associated taxa across all RS‐fed mice. In addition, major changes were observed for metabolites solely or primarily metabolized in the gut (e.g., trimethylamine‐N‐oxide), metabolites that have a significant entero‐hepatic circulation (i.e., bile acids), lipid metabolites (e.g., cholesterol sulfate), metabolites indicating increased energy turnover (e.g., tricarboxylic acid cycle intermediates and ketone bodies), and increased antioxidants such as reduced glutathione. Our findings reveal potentially novel mediators of high microbiome‐accessible carbohydrate‐derived health benefits.—Koay,Y. C., Wali. J. A., Luk, A. W. S., Macia, L., Cogger, V. C., Pulpitel, T. J., Wahl, D., Solon‐Biet, S. M., Holmes, A., Simpson, S. J., O'Sullivan, J. F. Ingestion of resistant starch by mice markedly increases microbiome‐derived metabolites. FASEB J. 33, 8033–8042 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Ingestion of resistant starch by mice markedly increases microbiome‐derived metabolites

et al. 2019

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“…Recently, NKT cells were shown to be strongly activated, particularly by the primary BA tauro‐β‐muricholic acid . Moreover, FXR agonists have now been approved as therapeutic agents for NASH, and it is expected that signals from this nuclear transcription factor suppress lipogenic and fibrotic signals in the liver . Elucidation of the detailed molecular mechanisms linked to gut microbial metabolites by the gut–liver axis may lead to the development of promising preventive and therapeutic drugs using advanced techniques for liver diseases.…”

Section: Resultsmentioning

confidence: 99%

“…FXR activation reduces the excess BA pool in the hepatocyte, thereby preventing cholestasis and/or accumulation of toxic secondary BAs, such as DCA and LTA . FXR also stimulates the production of FGF15 (mice) or 19 (human) which, after binding to FGF receptor 4 in liver cells, represses BA synthesis and promotes hepatic glycogen storage and fatty acid oxidation . BAs also activate TGR5 in muscle and adipose tissues, increasing thermogenesis and energy expenditure.…”

Section: Gut Microbiota and Nashmentioning

confidence: 99%

“…BAs also activate TGR5 in muscle and adipose tissues, increasing thermogenesis and energy expenditure. Moreover, activation of TGR5 in the intestine promotes glucagon‐like peptide 1 release from L cells, promoting insulin release from pancreatic β cells . Signaling from another nuclear receptor, constitutive androstane receptor (CAR), was shown to activate ß‐catenin signaling, thereby promoting NASH‐associated liver cancer .…”

Section: Gut Microbiota and Nashmentioning

confidence: 99%

“…On the other hand, lipopolysaccharide (LPS), an outer membrane component of gram‐negative bacteria, and lipoteichoic acid (LTA), a cell wall component of gram‐positive bacteria, interact with toll‐like receptor (TLR) 4 and TLR2, respectively, and induce inflammation by innate immune responses, facilitating liver fibrosis and cancer depending on the physiological context . Moreover, bile acids (BAs) modulate metabolic pathways in hepatocytes or intestinal epithelial cells through nuclear receptor transcription factors by acting as their ligands to maintain the homeostasis of the liver . However, the excess amount of secondary BAs, such as deoxycholic acid (DCA) and lithocholic acid (LCA) produced by gut microbiota, provokes liver damage and induces stress response signaling, thereby possibly promoting liver cancer …”

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confidence: 99%

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Role of the Gut–Liver Axis in Liver Inflammation, Fibrosis, and Cancer: A Special Focus on the Gut Microbiota Relationship

2019

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The gut and the liver are anatomically and physiologically connected, and this “gut–liver axis” exerts various influences on liver pathology. The gut microbiota consists of various microorganisms that normally coexist in the human gut and have a role of maintaining the homeostasis of the host. However, once homeostasis is disturbed, metabolites and components derived from the gut microbiota translocate to the liver and induce pathologic effects in the liver. In this review, we introduce and discuss the mechanisms of liver inflammation, fibrosis, and cancer that are influenced by gut microbial components and metabolites; we include recent advances in molecular‐based therapeutics and novel mechanistic findings associated with the gut–liver axis and gut microbiota.

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Bile acid profiles in bile and feces of obese mice by a high‐performance liquid chromatography–tandem mass spectrometry

Zheng

Cheng²,

et al. 2020

Biotechnology and Applied Biochemistry

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Bile acids (BAs) play a pivotal role in manipulating the development of metabolic diseases. However, due to the compositional complexity and functional variation of BAs, it remains unclear about the changes in BA pool for individuals with obesity or metabolic syndrome. We established a high-performance liquid chromatography-mass spectrometer detection system for the simultaneous analysis of both unconjugated and conjugated BAs in the bile and feces of mice. Ten BAs were completely separated, identified, and quantified with low limit of detection (0.5 ng/mL) and inter/intraday precision (relative standard deviation < 12%). By using this method, these BAs in bile and feces of mice were quantified. The result showed that taurochenodeoxycholic acid, taurine-conjugated α-muricholic acids, and taurine-conjugated β-muricholic acids were the dominated BAs in bile, whereas deoxycholic acid and chenodeoxycholic acid predominated in feces. Further, most of the BA levels were significantly elevated in either bile or fecal samples of high-fat diet-fed mice as compared with those in normal chow diet-fed mice, indicating that excessive production of BAs was closely associated with the occurrence of lipid metabolism disorders. In summary, the present method is practicable for analysis of BAs in bile and fecal samples of patients with obesity.

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Bile acids in glucose metabolism in health and disease

Cited by 316 publications

References 148 publications

Ingestion of resistant starch by mice markedly increases microbiome‐derived metabolites

Ingestion of resistant starch by mice markedly increases microbiome‐derived metabolites

Role of the Gut–Liver Axis in Liver Inflammation, Fibrosis, and Cancer: A Special Focus on the Gut Microbiota Relationship

Bile acid profiles in bile and feces of obese mice by a high‐performance liquid chromatography–tandem mass spectrometry

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