Bile Acid-Activated Receptors, Intestinal Microbiota, and the Treatment of Metabolic Disorders

Structure, function and diversity of the healthy human microbiome

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A human gut microbial gene catalogue established by metagenomic sequencing

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Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences

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Human gut microbes associated with obesity

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Enterotypes of the human gut microbiome

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Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells

Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., et al. (2013) · Nature · doi:10.1038/nature12721 · Cited by 5,549 · see citing works

The Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic T _reg Cell Homeostasis

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Host-gut microbiota metabolic interactions

Nicholson, J. K., Holmes, E., Kinross, J., Burcelin, R., Gibson, G., Jia, W., & Pettersson, S. (2012) · Science · doi:10.1126/science.1223813 · Cited by 4,760 · see citing works

Richness of human gut microbiome correlates with metabolic markers

Le Chatelier, E., Nielsen, T., Qin, J., Prifti, E., Hildebrand, F., Falony, G., Almeida, M., Arumugam, M., Batto, J.-M., Kennedy, S., et al. (2013) · Nature · doi:10.1038/nature12506 · Cited by 4,662 · see citing works

The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

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Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice

Ridaura, V. K., Faith, J. J., Rey, F. E., Cheng, J., Duncan, A. E., Kau, A. L., Griffin, N. W., Lombard, V., Henrissat, B., Bain, J. R., et al. (2013) · Science · doi:10.1126/science.1241214 · Cited by 3,788 · see citing works

The impact of the gut microbiota on human health: an integrative view

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Bile salt biotransformations by human intestinal bacteria

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Identification of a nuclear receptor for bile acids

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Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist

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Bile Acids: Natural Ligands for an Orphan Nuclear Receptor

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Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): A multicentre, randomised, placebo-controlled trial

Neuschwander-Tetri, B. A., Loomba, R., Sanyal, A. J., Lavine, J. E., Van Natta, M. L., Abdelmalek, M. F., Chalasani, N., Dasarathy, S., Diehl, A. M., Hameed, B., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(14)61933-4 · Cited by 2,237 · see citing works

Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation

Watanabe, M., Houten, S. M., Mataki, C., Christoffolete, M. A., Kim, B. W., Sato, H., Messaddeq, N., Harney, J. W., Ezaki, O., Kodama, T., et al. (2006) · Nature · doi:10.1038/nature04330 · Cited by 2,220 · see citing works

Microbiota-Generated Metabolites Promote Metabolic Benefits via Gut-Brain Neural Circuits

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An integrated catalog of reference genes in the human gut microbiome

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A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis

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Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile

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Endogenous Bile Acids Are Ligands for the Nuclear Receptor FXR/BAR

Wang, H., Chen, J., Hollister, K., Sowers, L. C., & Forman, B. M. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80348-2 · Cited by 1,636 · see citing works

A G Protein-coupled Receptor Responsive to Bile Acids

Kawamata, Y., Fujii, R., Hosoya, M., Harada, M., Yoshida, H., Miwa, M., Fukusumi, S., Habata, Y., Itoh, T., Shintani, Y., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209706200 · Cited by 1,628 · see citing works

Bile acids: regulation of synthesis

Chiang, J. Y. L. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r900010-jlr200 · Cited by 1,567 · see citing works

The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity

Staudinger, J. L., Goodwin, B. J., Jones, S. A., Hawkins‐Brown, D., MacKenzie, K. I., Latour, A. M., Liu, Y., Klaassen, C. D., Brown, K. K., Reinhard, J. F., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051551698 · Cited by 1,378 · see citing works

Vitamin D Receptor As an Intestinal Bile Acid Sensor

Makishima, M., Lu, T. T., Xie, W., Whitfield, G. K., Domoto, H., Evans, R. M., Haussler, M. R., & Mangelsdorf, D. J. (2002) · Science · doi:10.1126/science.1070477 · Cited by 1,176 · see citing works

Differential Adaptation of Human Gut Microbiota to Bariatric Surgery–Induced Weight Loss

Furet, J.-P., Kong, L.-C., Tap, J., Poitou, C., Basdevant, A., Bouillot, J.-L., Mariat, D., Corthier, G., Doré, J., Henegar, C., et al. (2010) · Diabetes · doi:10.2337/db10-0253 · Cited by 1,173 · see citing works

Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor

Inagaki, T., Moschetta, A., Lee, Y.-K., Peng, L., Zhao, G., Downes, M., Yu, R. T., Shelton, J. M., Richardson, J. A., Repa, J. J., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509592103 · Cited by 1,164 · see citing works

FXR is a molecular target for the effects of vertical sleeve gastrectomy

Ryan, K. K., Tremaroli, V., Clemmensen, C., Kovatcheva-Datchary, P., Myronovych, A., Karns, R., Wilson-Pérez, H. E., Sandoval, D. A., Kohli, R., Bäckhed, F., et al. (2014) · Nature · doi:10.1038/nature13135 · Cited by 931 · see citing works

Bile Acid Is a Host Factor That Regulates the Composition of the Cecal Microbiota in Rats

Islam, K. B. M. S., Fukiya, S., Hagio, M., Fujii, N., Ishizuka, S., Ooka, T., Ogura, Y., Hayashi, T., & Yokota, A. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.07.046 · Cited by 918 · see citing works

Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1

Katsuma, S., Hirasawa, A., & Tsujimoto, G. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.01.139 · Cited by 789 · see citing works

Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance

Fang, S., Suh, J. M., Reilly, S. M., Yu, E., Osborn, O., Lackey, D., Yoshihara, E., Perino, A., Jacinto, S., Lukasheva, Y., et al. (2015) · Nature Medicine · doi:10.1038/nm.3760 · Cited by 738 · see citing works

Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity

Li, F., Jiang, C., Krausz, K. W., Li, Y., Albert, I., Hao, H., Fabre, K. M., Mitchell, J. B., Patterson, A. D., & Gonzalez, F. J. (2013) · Nature Communications · doi:10.1038/ncomms3384 · Cited by 705 · see citing works

Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease

Jiang, C., Xie, C., Li, F., Zhang, L., Nichols, R. G., Krausz, K. W., Cai, J., Qi, Y., Fang, Z.-Z., Takahashi, S., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci76738 · Cited by 693 · see citing works

The bile acid receptor FXR is a modulator of intestinal innate immunity

Vavassori, P., Mencarelli, A., Renga, B., Distrutti, E., & Fiorucci, S. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803978 · Cited by 655 · see citing works

Enterohepatic bile salt transporters in normal physiology and liver disease

Kullak-Ublick, G. A., Stieger, B., & Meier, P. J. (2003) · Gastroenterology · doi:10.1053/j.gastro.2003.06.005 · Cited by 651 · see citing works

Bacterial colonization factors control specificity and stability of the gut microbiota

Lee, S. M., Donaldson, G. P., Mikulski, Z., Boyajian, S., Ley, K. F., & Mazmanian, S. K. (2013) · Nature · doi:10.1038/nature12447 · Cited by 629 · see citing works

Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid

Hirschfield, G. M., Mason, A., Luketic, V., Lindor, K., Gordon, S. C., Mayo, M., Kowdley, K. V., Vincent, C., Bodhenheimer, H. C., Parés, A., et al. (2015) · Gastroenterology · doi:10.1053/j.gastro.2014.12.005 · Cited by 576 · see citing works

Burden of Clostridium difficile on the Healthcare System

Dubberke, E. R., & Olsen, M. A. A. (2012) · Clinical Infectious Diseases · doi:10.1093/cid/cis335 · Cited by 558 · see citing works

Nutrient-sensing nuclear receptors coordinate autophagy

Lee, J. M., Wagner, M., Xiao, R., Kim, K. H., Feng, D., Lazar, M. A., & Moore, D. D. (2014) · Nature · doi:10.1038/nature13961 · Cited by 514 · see citing works

Redundant Pathways for Negative Feedback Regulation of Bile Acid Production

Wang, L., Lee, Y., Bundman, D. S., Han, Y., Thevananther, S., Kim, C.-S., Chua, S. S., Wei, P. Y., Heyman, R. A., Karin, M., et al. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00187-9 · Cited by 475 · see citing works

Metagenomic sequencing of the human gut microbiome before and after bariatric surgery in obese patients with type 2 diabetes: correlation with inflammatory and metabolic parameters

Graessler, J., Qin, Y., Zhong, H., Zhang, J., Licinio, J., Wong, M.-L., Xu, A., Chavakis, T., Bornstein, A. B., Ehrhart-Bornstein, M., et al. (2013) · The Pharmacogenomics Journal · doi:10.1038/tpj.2012.43 · Cited by 428 · see citing works

Transcriptional regulation of autophagy by an FXR–CREB axis

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The bile acid receptor GPBAR-1 (TGR5) modulates integrity of intestinal barrier and immune response to experimental colitis

Cipriani, S., Mencarelli, A., Chini, M. G., Distrutti, E., Renga, B., Bifulco, G., Baldelli, F., Donini, A., & Fiorucci, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025637 · Cited by 382 · see citing works

Microbiota Modification with Probiotics Induces Hepatic Bile Acid Synthesis via Downregulation of the Fxr-Fgf15 Axis in Mice

Degirolamo, C., Rainaldi, S., Bovenga, F., Murzilli, S., & Moschetta, A. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.02.032 · Cited by 356 · see citing works

Identification of a Bile Acid-responsive Element in the Human Ileal Bile Acid-binding Protein Gene

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Cirrhosis, bile acids and gut microbiota: Unraveling a complex relationship

Ridlon, J. M., Alves, J. M., Hylemon, P. B., & Bajaj, J. S. (2013) · Gut Microbes · doi:10.4161/gmic.25723 · Cited by 336 · see citing works

Gastric Bypass Surgery Enhances Glucagon-Like Peptide 1–Stimulated Postprandial Insulin Secretion in Humans

Salehi, M., Prigeon, R. L., & D’Alessio, D. A. (2011) · Diabetes · doi:10.2337/db11-0203 · Cited by 323 · see citing works

Conjugated Bile Acids Activate the Sphingosine–1–Phosphate Receptor 2 in Primary Rodent Hepatocytes

Studer, E. J., Zhou, X., Zhao, R., Wang, Y., Takabe, K., Nagahashi, M., Pandak, W. M., Dent, P., Spiegel, S., Shi, R., et al. (2011) · Hepatology · doi:10.1002/hep.24681 · Cited by 319 · see citing works

Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity

Mueller, M., Thorell, A., Claudel, T., Jha, P., Köfeler, H. C., Lackner, C., Hoesel, B., Fauler, G., Stojaković, T., Einarsson, C., et al. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2014.12.034 · Cited by 314 · see citing works

A Novel Constitutive Androstane Receptor-Mediated and CYP3A-Independent Pathway of Bile Acid Detoxification

Saini, S. P. S., Sonoda, J., Xu, L., Toma, D., Uppal, H., Mu, Y., Ren, S., Moore, D. D., Evans, R. M., & Xie, W. (2004) · Molecular Pharmacology · doi:10.1124/mol.65.2.292 · Cited by 250 · see citing works

Analyses of the Stability and Core Taxonomic Memberships of the Human Microbiome

Li, K., Bihan, M., & Methé, B. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0063139 · Cited by 235 · see citing works

Five-Year Outcomes After Laparoscopic Gastric Bypass and Laparoscopic Duodenal Switch in Patients With Body Mass Index of 50 to 60

Risstad, H., Søvik, T. T., Engström, M., Aasheim, E. T., Fagerland, M. W., Olsén, M. F., Kristinsson, J. A., le Roux, C. W., Bøhmer, T., Birkeland, K. I., et al. (2015) · JAMA Surgery · doi:10.1001/jamasurg.2014.3579 · Cited by 229 · see citing works

Modulation of Intestinal Microbiota by the Probiotic VSL#3 Resets Brain Gene Expression and Ameliorates the Age-Related Deficit in LTP

Distrutti, E., O’Reilly, J.-A., McDonald, C., Cipriani, S., Renga, B., Lynch, M. A., & Fiorucci, S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106503 · Cited by 207 · see citing works

Enteric Microbiome Metabolites Correlate with Response to Simvastatin Treatment

Kaddurah-Daouk, R., Baillie, R. A., Zhu, H., Zeng, Z.-B., Wiest, M. M., Nguyen, U. T., Wojnoonski, K., Watkins, S. M., Trupp, M., & Krauss, R. M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025482 · Cited by 193 · see citing works

Bile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery

Flynn, C. R., Albaugh, V. L., Cai, S. B., Cheung‐Flynn, J., Williams, P. E., Brucker, R. M., Bordenstein, S. R., Guo, Y. P., Wasserman, D. H., & Abumrad, N. N. (2015) · Nature Communications · doi:10.1038/ncomms8715 · Cited by 177 · see citing works

PPARα-UGT axis activation represses intestinal FXR-FGF15 feedback signalling and exacerbates experimental colitis

Zhou, X., Cao, L., Jiang, C., Xie, Y., Cheng, X., Krausz, K. W., Qi, Y., Sun, L., Shah, Y. M., Gonzalez, F. J., et al. (2014) · Nature Communications · doi:10.1038/ncomms5573 · Cited by 163 · see citing works

On the Evolutionary Origins of Obesity: A New Hypothesis

Sellayah, D., Cagampang, F. R. A., & Cox, R. (2014) · Endocrinology · doi:10.1210/en.2013-2103 · Cited by 141 · see citing works

Selective activation of liver X receptor alpha by 6α-hydroxy bile acids and analogs

Song, C. (2000) · Steroids · doi:10.1016/s0039-128x(00)00127-6 · Cited by 126 · see citing works

VSL#3 Resets Insulin Signaling and Protects against NASH and Atherosclerosis in a Model of Genetic Dyslipidemia and Intestinal Inflammation

Mencarelli, A., Cipriani, S., Renga, B., Bruno, A. M., D’Amore, C., Distrutti, E., & Fiorucci, S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045425 · Cited by 115 · see citing works

Probiotics Modulate Intestinal Expression of Nuclear Receptor and Provide Counter-Regulatory Signals to Inflammation-Driven Adipose Tissue Activation

Mencarelli, A., Distrutti, E., Renga, B., D’Amore, C., Cipriani, S., Palladino, G., Donini, A., Ricci, P., & Fiorucci, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022978 · Cited by 97 · see citing works

Modification on Ursodeoxycholic Acid (UDCA) Scaffold. Discovery of Bile Acid Derivatives As Selective Agonists of Cell-Surface G-Protein Coupled Bile Acid Receptor 1 (GP-BAR1)

Sepe, V., Renga, B., Festa, C., D’Amore, C., Masullo, D., Cipriani, S., Leva, F. S. D., Monti, M. C., Novellino, E., Limongelli, V., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500889f · Cited by 88 · see citing works

Exploitation of Cholane Scaffold for the Discovery of Potent and Selective Farnesoid X Receptor (FXR) and G‑Protein Coupled Bile Acid Receptor 1 (GP-BAR1) Ligands

Festa, C., Renga, B., D’Amore, C., Sepe, V., Finamore, C., Marino, S. D., Carino, A., Cipriani, S., Monti, M. C., Zampella, A., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm501273r · Cited by 84 · see citing works

Farnesoid X Receptor Agonist for the Treatment of Liver and Metabolic Disorders: Focus on 6-ethyl-CDCA

Fiorucci, S., Cipriani, S., Mencarelli, A., Baldelli, F., Bifulco, G., & Zampella, A. (2011) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/138955711796355258 · Cited by 76 · see citing works

Administration of Ampicillin Elevates Hepatic Primary Bile Acid Synthesis through Suppression of Ileal Fibroblast Growth Factor 15 Expression

Miyata, M., Takamatsu, Y., Kuribayashi, H., & Yamazoe, Y. (2009) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.160093 · Cited by 72 · see citing works

Dissociation of Intestinal and Hepatic Activities of FXR and LXRα Supports Metabolic Effects of Terminal Ileum Interposition in Rodents

Mencarelli, A., Renga, B., D’Amore, C., Santorelli, C., Graziosi, L., Bruno, A. M., Monti, M. C., Distrutti, E., Cipriani, S., Donini, A., et al. (2013) · Diabetes · doi:10.2337/db13-0299 · Cited by 63 · see citing works

Impaired Itching Perception in Murine Models of Cholestasis Is Supported by Dysregulation of GPBAR1 Signaling

Cipriani, S., Renga, B., D’Amore, C., Simonetti, M., Tursi, A. A. D., Carino, A., Monti, M. C., Sepe, V., Zampella, A., & Fiorucci, S. (2015) · PLoS ONE · doi:10.1371/journal.pone.0129866 · Cited by 54 · see citing works

Targeting FXR in cholestasis: hype or hope

Fiorucci, S., Distrutti, E., Ricci, P., Giuliano, V., Donini, A., & Baldelli, F. (2014) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2014.956087 · Cited by 53 · see citing works

Deoxycholic Acid Conjugates Are Muscarinic Cholinergic Receptor Antagonists

Raufman, J.-P., Chen, Y., Zimniak, P., & Cheng, K. (2002) · Pharmacology · doi:10.1159/000064347 · Cited by 47 · see citing works

Steroidal Scaffolds as FXR and GPBAR1 Ligands: From Chemistry to Therapeutical Application

Sepe, V., Distrutti, E., Limongelli, V., Fiorucci, S., & Zampella, A. (2015) · Future Medicinal Chemistry · doi:10.4155/fmc.15.54 · Cited by 37 · see citing works

Relationship of symptom duration and fecal bacteriotherapy inClostridium difficileinfection-pooled data analysis and a systematic review

Sofi, A. A., Silverman, A. L., Khuder, S., Garborg, K. K., Westerink, J. M. A., & Nawras, A. T. (2012) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365521.2012.743585 · Cited by 31 · see citing works

Gut-specific FXR agonism

Osório, J. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.4 · Cited by 3 · see citing works

Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis

Song, X., Sun, X., Oh, S. F., Wu, M., Zhang, Y., Zheng, W., Geva-Zatorsky, N., Jupp, R., Mathis, D., Benoist, C., et al. (2020) · Nature · doi:10.1038/s41586-019-1865-0 · Cited by 1,024 · see citing works

The role of short-chain fatty acids in the interplay between gut microbiota and diet in cardio-metabolic health

Nogal, A., Valdes, A. M., & Menni, C. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1897212 · Cited by 917 · see citing works

Bile Acids Control Inflammation and Metabolic Disorder through Inhibition of NLRP3 Inflammasome

Guo, C., Xie, S., Chi, Z., Zhang, J., Liu, Y., Zhang, L., Zheng, M., Zhang, X., Xia, D., Ke, Y., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.09.008 · Cited by 838 · see citing works

Mechanisms and consequences of intestinal dysbiosis

Weiss, G. A., & Hennet, T. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2509-x · Cited by 775 · see citing works

Human gut bacteria produce ΤΗ17-modulating bile acid metabolites

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