The Gut Microbial Bile Acid Modulation and Its Relevance to Digestive Health and Diseases

The human gut microbiome has been linked to numerous digestive disorders, but its metabolic products have been much less well characterized, in part due to the expense of untargeted metabolomics and lack of ability to process the data. In this review, we focused on the rapidly expanding information about the bile acid repertoire produced by the gut microbiome, including the impacts of bile acids on a wide range of host physiological processes and diseases, and discussed the role of short-chain fatty acids and other important gut microbiome–derived metabolites. Of particular note is the action of gut microbiome–derived metabolites throughout the body, which impact processes ranging from obesity to aging to disorders traditionally thought of as diseases of the nervous system, but that are now recognized as being strongly influenced by the gut microbiome and the metabolites it produces. We also highlighted the emerging role for modifying the gut microbiome to improve health or to treat disease, including the “engineered native bacteria” approach that takes bacterial strains from a patient, modifies them to alter metabolism, and reintroduces them. Taken together, study of the metabolites derived from the gut microbiome provided insights into a wide range of physiological and pathophysiological processes, and has substantial potential for new approaches to diagnostics and therapeutics of disease of, or involving, the gastrointestinal tract.

[1]  J. Crawford,et al.  Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites , 2022, Science.

[2]  Karam R. Motawea,et al.  Efficacy and safety of fecal microbiota transplant in irritable bowel syndrome: An update based on meta‐analysis of randomized control trials , 2022, Health science reports.

[3]  Yousong Ding,et al.  Methods of DNA Introduction for the Engineering of Commensal Microbes , 2022, Engineering Microbiology.

[4]  A. Saghatelian,et al.  Diet and feeding pattern modulate diurnal dynamics of the ileal microbiome and transcriptome , 2022, Cell reports.

[5]  Ming-Shiang Wu,et al.  Alteration of Gut Microbial Metabolites in the Systemic Circulation of Patients with Parkinson's Disease. , 2022, Journal of Parkinson's disease.

[6]  K. Nie,et al.  TGR5 Agonist INT-777 Alleviates Inflammatory Neurodegeneration in Parkinson’s Disease Mouse Model by Modulating Mitochondrial Dynamics in Microglia , 2022, Neuroscience.

[7]  E. Pamer,et al.  Microbiome-based therapeutics , 2022, Nature Reviews Microbiology.

[8]  J. Hasty,et al.  Intestinal transgene delivery with native E. coli chassis allows persistent physiological changes , 2021, Cell.

[9]  D. O’Malley,et al.  Aberrant Gut-To-Brain Signaling in Irritable Bowel Syndrome - The Role of Bile Acids , 2021, Frontiers in Endocrinology.

[10]  Bangmao Wang,et al.  Gut microbiota-derived short-chain fatty acids and colorectal cancer: Ready for clinical translation? , 2021, Cancer letters.

[11]  Emily C. Gentry,et al.  High-confidence structural annotation of metabolites absent from spectral libraries , 2021, Nature Biotechnology.

[12]  Qin Liu,et al.  Gut Microbiota-Derived Metabolites in Irritable Bowel Syndrome , 2021, Frontiers in Cellular and Infection Microbiology.

[13]  P. Dorrestein,et al.  Mass spectrometry-based metabolomics in microbiome investigations , 2021, Nature Reviews Microbiology.

[14]  J. Keenan,et al.  Concentrations of Fecal Bile Acids in Participants with Functional Gut Disorders and Healthy Controls , 2021, Metabolites.

[15]  Emily C. Gentry,et al.  A Synthesis-Based Reverse Metabolomics Approach for the Discovery of Chemical Structures from Humans and Animals. , 2021 .

[16]  A. Sutton,et al.  Nutritional supplementation for nonalcohol-related fatty liver disease: a network meta-analysis. , 2021, The Cochrane database of systematic reviews.

[17]  Haojun Yang,et al.  TGR5 protects against cholestatic liver disease via suppressing the NF-κB pathway and activating the Nrf2/HO-1 pathway , 2021, Annals of translational medicine.

[18]  J. Wilkinson,et al.  Irritable Bowel Syndrome: Questions and Answers for Effective Care. , 2021, American family physician.

[19]  K. McVey Neufeld,et al.  Animal models of visceral pain and the role of the microbiome , 2021, Neurobiology of pain.

[20]  E. Chang,et al.  Gut microbiota as a transducer of dietary cues to regulate host circadian rhythms and metabolism , 2021, Nature Reviews Gastroenterology & Hepatology.

[21]  Kaichun Wu,et al.  Fecal Microbiota Transplantation as Therapy for Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis , 2021, Gastroenterology research and practice.

[22]  Yongheng Chen,et al.  Farnesoid X receptor (FXR): Structures and ligands , 2021, Computational and structural biotechnology journal.

[23]  Mingxun Wang,et al.  Chemical Proportionality within Molecular Networks. , 2021, Analytical chemistry.

[24]  John C. Earls,et al.  Gut microbiome pattern reflects healthy ageing and predicts survival in humans , 2021, Nature Metabolism.

[25]  Guowang Xu,et al.  Comprehensive metabolic profiling of Parkinson’s disease by liquid chromatography-mass spectrometry , 2021, Molecular neurodegeneration.

[26]  Irving E. Vega,et al.  Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson’s Disease , 2021, Metabolites.

[27]  C. López-Otín,et al.  Hallmarks of Health , 2020, Cell.

[28]  Michele Biagioli,et al.  Bile Acid Signaling in Inflammatory Bowel Diseases , 2020, Digestive Diseases and Sciences.

[29]  Wei Wei,et al.  Altered metabolism of bile acids correlates with clinical parameters and the gut microbiota in patients with diarrhea-predominant irritable bowel syndrome , 2020, World journal of gastroenterology.

[30]  J. Griffin,et al.  Metabolomic Analysis in Inflammatory Bowel Disease: A Systematic Review. , 2020, Journal of Crohn's & colitis.

[31]  S. Ishihara,et al.  Molecular Mechanisms of Microbiota-Mediated Pathology in Irritable Bowel Syndrome , 2020, International journal of molecular sciences.

[32]  F. Bishehsari,et al.  Circadian rhythms and the gut microbiota: from the metabolic syndrome to cancer , 2020, Nature Reviews Endocrinology.

[33]  C. Quince,et al.  The pathophysiology of bile acid diarrhoea: differences in the colonic microbiome, metabolome and bile acids , 2020, Scientific Reports.

[34]  Haiyang Xie,et al.  A novel role for farnesoid X receptor in the bile acid‐mediated intestinal glucose homeostasis , 2020, Journal of cellular and molecular medicine.

[35]  Krishna R. Kalari,et al.  Longitudinal Multi-omics Reveals Subset-Specific Mechanisms Underlying Irritable Bowel Syndrome , 2020, Cell.

[36]  M. Heitkemper,et al.  Bile Acids and Microbiome Among Individuals With Irritable Bowel Syndrome and Healthy Volunteers , 2020, Biological research for nursing.

[37]  Emmanuel O. Elijah,et al.  Paroxetine Administration Affects Microbiota and Bile Acid Levels in Mice , 2020, Frontiers in Psychiatry.

[38]  Ashley M Sidebottom,et al.  IBD Microbial Metabolome: The Good, Bad, and Unknown , 2020, Trends in Endocrinology & Metabolism.

[39]  M. Charbonneau,et al.  Developing a new class of engineered live bacterial therapeutics to treat human diseases , 2020, Nature Communications.

[40]  K. Clément,et al.  Gut microbiota and human NAFLD: disentangling microbial signatures from metabolic disorders , 2020, Nature Reviews Gastroenterology & Hepatology.

[41]  Julie C. Lumeng,et al.  Global chemical effects of the microbiome include new bile-acid conjugations , 2020, Nature.

[42]  H. Sokol,et al.  Gut microbiota-derived metabolites as key actors in inflammatory bowel disease , 2020, Nature Reviews Gastroenterology & Hepatology.

[43]  Laxmi Parida,et al.  Human Skin, Oral, and Gut Microbiomes Predict Chronological Age , 2020, mSystems.

[44]  Justin J. J. van der Hooft,et al.  Mass spectrometry searches using MASST , 2020, Nature Biotechnology.

[45]  E. Chang,et al.  Intersection of the Gut Microbiome and Circadian Rhythms in Metabolism , 2020, Trends in Endocrinology & Metabolism.

[46]  Christine M. Aceves,et al.  Reproducible molecular networking of untargeted mass spectrometry data using GNPS , 2019, Nature Protocols.

[47]  F. Shanahan,et al.  Differences in Fecal Microbiomes and Metabolomes of People With vs Without Irritable Bowel Syndrome and Bile Acid Malabsorption. , 2019, Gastroenterology.

[48]  A. Farmer,et al.  Critical evaluation of animal models of visceral pain for therapeutics development: A focus on irritable bowel syndrome , 2019, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[49]  X. Fang,et al.  A Clostridia-rich microbiota enhances bile acid excretion in diarrhea-predominant irritable bowel syndrome , 2019, The Journal of clinical investigation.

[50]  Manfred von der Ohe,et al.  Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial , 2019, The Lancet.

[51]  J. Vendrell,et al.  Gut microbiota-derived succinate: Friend or foe in human metabolic diseases? , 2019, Reviews in Endocrine and Metabolic Disorders.

[52]  R. Haeusler,et al.  Bile acids in glucose metabolism and insulin signalling — mechanisms and research needs , 2019, Nature Reviews Endocrinology.

[53]  C. Beaudoin,et al.  Farnesoid X receptor alpha (FXRα) is a critical actor of the development and pathologies of the male reproductive system , 2019, Cellular and Molecular Life Sciences.

[54]  M. Schmulson,et al.  Fecal microbiota transplantation in irritable bowel syndrome: A systematic review and meta-analysis , 2019, United European gastroenterology journal.

[55]  M. Surette,et al.  Gut Microbiota in Patients With Irritable Bowel Syndrome-A Systematic Review. , 2019, Gastroenterology.

[56]  N. Bray The microbiota–gut–brain axis , 2019 .

[57]  M. Linterman,et al.  Heterochronic faecal transplantation boosts gut germinal centres in aged mice , 2019, Nature Communications.

[58]  R. Loomba,et al.  Review article: emerging role of the gut microbiome in the progression of nonalcoholic fatty liver disease and potential therapeutic implications , 2019, Alimentary pharmacology & therapeutics.

[59]  Liang Yao,et al.  The Clinical and Steroid-Free Remission of Fecal Microbiota Transplantation to Patients with Ulcerative Colitis: A Meta-Analysis , 2019, Gastroenterology research and practice.

[60]  A. Zorzano,et al.  SUCNR1 controls an anti-inflammatory program in macrophages to regulate the metabolic response to obesity , 2019, Nature Immunology.

[61]  M. Camilleri,et al.  Analysis of Fecal Primary Bile Acids Detects Increased Stool Weight and Colonic Transit in Patients With Chronic Functional Diarrhea , 2019, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[62]  R. Knight,et al.  A gut microbiome signature for cirrhosis due to nonalcoholic fatty liver disease , 2019, Nature Communications.

[63]  G. Farrugia,et al.  Serine proteases as luminal mediators of intestinal barrier dysfunction and symptom severity in IBS , 2019, Gut.

[64]  P. Higgins,et al.  Efficacy of Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis. , 2019, The American journal of gastroenterology.

[65]  Jaw-Yuan Wang,et al.  Fecal microbiota transplantation: Review and update. , 2019, Journal of the Formosan Medical Association = Taiwan yi zhi.

[66]  R. Evans,et al.  FXR Regulates Intestinal Cancer Stem Cell Proliferation , 2019, Cell.

[67]  Austin D. Swafford,et al.  Age- and Sex-Dependent Patterns of Gut Microbial Diversity in Human Adults , 2019, mSystems.

[68]  L. Duan,et al.  Alterations of Gut Microbiota in Patients With Irritable Bowel Syndrome Based on 16S rRNA-Targeted Sequencing: A Systematic Review , 2019, Clinical and translational gastroenterology.

[69]  D. Brenner,et al.  Serum bile acid patterns are associated with the presence of NAFLD in twins, and dose‐dependent changes with increase in fibrosis stage in patients with biopsy‐proven NAFLD , 2018, Alimentary pharmacology & therapeutics.

[70]  Wen-Ting Li,et al.  Bile acids induce visceral hypersensitivity via mucosal mast cell–to–nociceptor signaling that involves the farnesoid X receptor/nerve growth factor/transient receptor potential vanilloid 1 axis , 2018, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[71]  Eric A. Franzosa,et al.  Gut microbiome structure and metabolic activity in inflammatory bowel disease , 2018, Nature Microbiology.

[72]  P. Moayyedi,et al.  Systematic review with meta‐analysis: the efficacy of prebiotics, probiotics, synbiotics and antibiotics in irritable bowel syndrome , 2018, Alimentary pharmacology & therapeutics.

[73]  P. de Vos,et al.  Sex differences in lipid metabolism are affected by presence of the gut microbiota , 2018, Scientific Reports.

[74]  S. Aquila,et al.  Activated-farnesoid X receptor (FXR) expressed in human sperm alters its fertilising ability. , 2018, Reproduction.

[75]  Lingyan Ye,et al.  Niacin fine-tunes energy homeostasis through canonical GPR109A signaling , 2018, bioRxiv.

[76]  R. Knight,et al.  Antibiotic-induced microbiome depletion alters metabolic homeostasis by affecting gut signaling and colonic metabolism , 2018, Nature Communications.

[77]  Luke R. Thompson,et al.  Best practices for analysing microbiomes , 2018, Nature Reviews Microbiology.

[78]  Weston R. Whitaker,et al.  Gut Microbiota-Produced Tryptamine Activates an Epithelial G-Protein-Coupled Receptor to Increase Colonic Secretion. , 2018, Cell host & microbe.

[79]  Kathleen A Cronin,et al.  Annual Report to the Nation on the Status of Cancer, part I: National cancer statistics , 2018, Cancer.

[80]  Justine W. Debelius,et al.  The gut–liver axis and the intersection with the microbiome , 2018, Nature Reviews Gastroenterology & Hepatology.

[81]  V. Sepe,et al.  Farnesoid X receptor modulators 2014-present: a patent review , 2018, Expert opinion on therapeutic patents.

[82]  A. Rosa,et al.  Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson’s Disease , 2018, Molecular Neurobiology.

[83]  Rob Knight,et al.  Current understanding of the human microbiome , 2018, Nature Medicine.

[84]  S. Pluchino,et al.  Macrophage-Derived Extracellular Succinate Licenses Neural Stem Cells to Suppress Chronic Neuroinflammation , 2018, Cell stem cell.

[85]  D. Chinnapen,et al.  Targeting friend and foe: Emerging therapeutics in the age of gut microbiome and disease , 2018, Journal of Microbiology.

[86]  K. Katsanos,et al.  Role of bile acids in inflammatory bowel disease , 2018, Annals of gastroenterology.

[87]  H. Flint,et al.  Specific substrate-driven changes in human faecal microbiota composition contrast with functional redundancy in short-chain fatty acid production , 2017, The ISME Journal.

[88]  Jeffrey J. Tabor,et al.  Engineering Diagnostic and Therapeutic Gut Bacteria , 2017, Microbiology spectrum.

[89]  T. Dinan,et al.  Microbiota-related Changes in Bile Acid & Tryptophan Metabolism are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism , 2017, EBioMedicine.

[90]  S. Zeisel,et al.  Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease. , 2017, Annual review of nutrition.

[91]  E. Hsiao,et al.  The Microbiome and Host Behavior. , 2017, Annual review of neuroscience.

[92]  M. Nieto‐Sampedro,et al.  TUDCA: An Agonist of the Bile Acid Receptor GPBAR1/TGR5 With Anti‐Inflammatory Effects in Microglial Cells , 2017, Journal of cellular physiology.

[93]  P. Saha,et al.  Hepatic FXR/SHP axis modulates systemic glucose and fatty acid homeostasis in aged mice , 2017, Hepatology.

[94]  D. Francisci,et al.  The Bile Acid Receptor GPBAR1 Regulates the M1/M2 Phenotype of Intestinal Macrophages and Activation of GPBAR1 Rescues Mice from Murine Colitis , 2017, The Journal of Immunology.

[95]  R. Knight,et al.  Global chemical analysis of biology by mass spectrometry , 2017 .

[96]  A. Petrescu,et al.  Bile Acid-Mediated Sphingosine-1-Phosphate Receptor 2 Signaling Promotes Neuroinflammation during Hepatic Encephalopathy in Mice , 2017, Front. Cell. Neurosci..

[97]  B. Staels,et al.  Bile acid control of metabolism and inflammation in obesity, type 2 diabetes, dyslipidemia and NAFLD. , 2017 .

[98]  M. Surette,et al.  Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction , 2017, Cell host & microbe.

[99]  G. Farrugia,et al.  Human-derived gut microbiota modulates colonic secretion in mice by regulating 5-HT3 receptor expression via acetate production. , 2017, American journal of physiology. Gastrointestinal and liver physiology.

[100]  J. Chiang,et al.  G‐protein‐coupled bile acid receptor plays a key role in bile acid metabolism and fasting‐induced hepatic steatosis in mice , 2017, Hepatology.

[101]  C. Gahan,et al.  Disease-Associated Changes in Bile Acid Profiles and Links to Altered Gut Microbiota , 2017, Digestive Diseases.

[102]  M. Surette,et al.  Transplantation of fecal microbiota from patients with irritable bowel syndrome alters gut function and behavior in recipient mice , 2017, Science Translational Medicine.

[103]  J. Chiang,et al.  Intestinal Farnesoid X Receptor and Takeda G Protein Couple Receptor 5 Signaling in Metabolic Regulation , 2017, Digestive Diseases.

[104]  D. Antonopoulos,et al.  Mutual reinforcement of pathophysiological host‐microbe interactions in intestinal stasis models , 2017, Physiological reports.

[105]  G. Guo,et al.  Role of FXR in Liver Inflammation During Nonalcoholic Steatohepatitis , 2017, Current Pharmacology Reports.

[106]  P. Kashyap,et al.  Irritable bowel syndrome: a gut microbiota-related disorder? , 2017, American journal of physiology. Gastrointestinal and liver physiology.

[107]  M. Nieto‐Sampedro,et al.  TGFβ Contributes to the Anti-inflammatory Effects of Tauroursodeoxycholic Acid on an Animal Model of Acute Neuroinflammation , 2017, Molecular Neurobiology.

[108]  S. Lynch,et al.  The Human Intestinal Microbiome in Health and Disease. , 2016, The New England journal of medicine.

[109]  F. Shanahan,et al.  Unconjugated Bile Acids Influence Expression of Circadian Genes: A Potential Mechanism for Microbe-Host Crosstalk , 2016, PloS one.

[110]  Rob Knight,et al.  Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease , 2016, Cell.

[111]  Timothy K Lu,et al.  Microbiome therapeutics - Advances and challenges. , 2016, Advanced drug delivery reviews.

[112]  Hanns-Ulrich Marschall,et al.  Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism. , 2016, Cell metabolism.

[113]  F. Bäckhed,et al.  From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites , 2016, Cell.

[114]  E. Comelli,et al.  Bile Acids and Dysbiosis in Non-Alcoholic Fatty Liver Disease , 2016, PloS one.

[115]  Oluf Pedersen,et al.  Alterations in fecal microbiota composition by probiotic supplementation in healthy adults: a systematic review of randomized controlled trials , 2016, Genome Medicine.

[116]  P. Bork,et al.  Durable coexistence of donor and recipient strains after fecal microbiota transplantation , 2016, Science.

[117]  S. Kulling,et al.  Age-Related Changes of Plasma Bile Acid Concentrations in Healthy Adults—Results from the Cross-Sectional KarMeN Study , 2016, PloS one.

[118]  H. Gaskins,et al.  Taurocholic acid metabolism by gut microbes and colon cancer , 2016, Gut microbes.

[119]  F. Pattou,et al.  Bile Diversion in Roux-en-Y Gastric Bypass Modulates Sodium-Dependent Glucose Intestinal Uptake. , 2016, Cell metabolism.

[120]  C. Gahan,et al.  Bile Acid Modifications at the Microbe-Host Interface: Potential for Nutraceutical and Pharmaceutical Interventions in Host Health. , 2016, Annual review of food science and technology.

[121]  A. Margolles,et al.  Intestinal Short Chain Fatty Acids and their Link with Diet and Human Health , 2016, Front. Microbiol..

[122]  K. Schoonjans,et al.  Bile acid-FXRα pathways regulate male sexual maturation in mice , 2016, Oncotarget.

[123]  Matthew McMillin,et al.  Bile Acid Signaling Is Involved in the Neurological Decline in a Murine Model of Acute Liver Failure. , 2016, The American journal of pathology.

[124]  Dong-Hyun Kim,et al.  Gut microbiota lipopolysaccharide accelerates inflamm-aging in mice , 2016, BMC Microbiology.

[125]  F. Bäckhed,et al.  Microbiota-induced obesity requires farnesoid X receptor , 2016, Gut.

[126]  P. Hylemon,et al.  Consequences of bile salt biotransformations by intestinal bacteria , 2016, Gut microbes.

[127]  William H. Bisson,et al.  Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction , 2015, Nature Communications.

[128]  Matthew McMillin,et al.  TGR5 signaling reduces neuroinflammation during hepatic encephalopathy , 2015, Journal of neurochemistry.

[129]  B. Hayee,et al.  Systematic review: bile acids and intestinal inflammation‐luminal aggressors or regulators of mucosal defence? , 2015, Alimentary pharmacology & therapeutics.

[130]  Rohit Loomba,et al.  Recommendations for Diagnosis, Referral for Liver Biopsy, and Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. , 2015, Mayo Clinic proceedings.

[131]  R. Carroll,et al.  In Vivo Regulation of Colonic Cell Proliferation, Differentiation, Apoptosis, and P27Kip1 by Dietary Fish Oil and Butyrate in Rats , 2015, Cancer Prevention Research.

[132]  I. Amit,et al.  Host microbiota constantly control maturation and function of microglia in the CNS , 2015, Nature Neuroscience.

[133]  J. Sonnenburg,et al.  Gut microbes promote colonic serotonin production through an effect of short‐chain fatty acids on enterochromaffin cells , 2015, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[134]  J. Murabito,et al.  Distinct Metabolomic Signatures Are Associated with Longevity in Humans , 2015, Nature Communications.

[135]  C. Lozupone,et al.  Gut bacteria in children with autism spectrum disorders: challenges and promise of studying how a complex community influences a complex disease , 2015, Microbial ecology in health and disease.

[136]  Leo Lahti,et al.  Fat, Fiber and Cancer Risk in African Americans and Rural Africans , 2015, Nature Communications.

[137]  D. Brenner,et al.  Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance , 2015, Nature Medicine.

[138]  J. Koenig,et al.  Microbial shifts in the aging mouse gut , 2014, Microbiome.

[139]  J. Chiang,et al.  Bile Acid Signaling in Metabolic Disease and Drug Therapy , 2014, Pharmacological Reviews.

[140]  R. Pellicciari,et al.  Beyond bile acids: targeting Farnesoid X Receptor (FXR) with natural and synthetic ligands. , 2014, Current topics in medicinal chemistry.

[141]  C. Hill,et al.  Bacterial bile salt hydrolase in host metabolism: Potential for influencing gastrointestinal microbe-host crosstalk , 2014, Gut microbes.

[142]  G. Marceau,et al.  Bile acids alter male fertility through G‐protein‐coupled bile acid receptor 1 signaling pathways in mice , 2014, Hepatology.

[143]  Matthew McMillin,et al.  Bile acids permeabilize the blood brain barrier after bile duct ligation in rats via Rac1-dependent mechanisms. , 2014, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[144]  D. Mukherji,et al.  Secondary bile acids: an underrecognized cause of colon cancer , 2014, World Journal of Surgical Oncology.

[145]  C. Hill,et al.  Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut , 2014, Proceedings of the National Academy of Sciences.

[146]  J. Tiedje,et al.  Revealing the Bacterial Butyrate Synthesis Pathways by Analyzing (Meta)genomic Data , 2014, mBio.

[147]  A. Rudensky,et al.  Microbial metabolites control gut inflammatory responses , 2014, Proceedings of the National Academy of Sciences.

[148]  F. Bäckhed,et al.  Microbiota-Generated Metabolites Promote Metabolic Benefits via Gut-Brain Neural Circuits , 2014, Cell.

[149]  M. Camilleri Advances in understanding of bile acid diarrhea , 2014, Expert review of gastroenterology & hepatology.

[150]  C. Mackay,et al.  The role of short-chain fatty acids in health and disease. , 2014, Advances in immunology.

[151]  J. Petrosino,et al.  Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders , 2013, Cell.

[152]  S. Rampelli,et al.  Functional metagenomic profiling of intestinal microbiome in extreme ageing , 2013, Aging.

[153]  F. Bäckhed,et al.  Microbial modulation of energy availability in the colon regulates intestinal transit. , 2013, Cell host & microbe.

[154]  Hong Liang,et al.  Bile Acids Modulate Signaling by Functional Perturbation of Plasma Membrane Domains* , 2013, The Journal of Biological Chemistry.

[155]  L. Brandt,et al.  An overview of fecal microbiota transplantation: techniques, indications, and outcomes. , 2013, Gastrointestinal endoscopy.

[156]  J. Chiang Bile acid metabolism and signaling. , 2013, Comprehensive Physiology.

[157]  Manuel Serrano,et al.  The Hallmarks of Aging , 2013, Cell.

[158]  Fredrik H. Karlsson,et al.  Gut metagenome in European women with normal, impaired and diabetic glucose control , 2013, Nature.

[159]  M. Bohlooly-y,et al.  Ageing Fxr Deficient Mice Develop Increased Energy Expenditure, Improved Glucose Control and Liver Damage Resembling NASH , 2013, PloS one.

[160]  P. Edwards,et al.  Pleiotropic roles of bile acids in metabolism. , 2013, Cell metabolism.

[161]  G. Tsujimoto,et al.  The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43 , 2013, Nature Communications.

[162]  Fei Li,et al.  FXR signaling in the enterohepatic system , 2013, Molecular and Cellular Endocrinology.

[163]  M. Dapoigny,et al.  The hypersensitivity to colonic distension of IBS patients can be transferred to rats through their fecal microbiota , 2013, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[164]  F. Bäckhed,et al.  Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. , 2013, Cell metabolism.

[165]  Wei Sun,et al.  The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. , 2012, Molecular cell.

[166]  H. Flint,et al.  Role of the gut microbiota in nutrition and health , 2018, British Medical Journal.

[167]  Qiang Feng,et al.  A metagenome-wide association study of gut microbiota in type 2 diabetes , 2012, Nature.

[168]  D. Sinderen,et al.  Gut microbiota composition correlates with diet and health in the elderly , 2012, Nature.

[169]  T. Hibi,et al.  Bile acids induce monocyte differentiation toward interleukin‐12 hypo‐producing dendritic cells via a TGR5‐dependent pathway , 2012, Immunology.

[170]  Rui F. M. Silva,et al.  Neuritic growth impairment and cell death by unconjugated bilirubin is mediated by NO and glutamate, modulated by microglia, and prevented by glycoursodeoxycholic acid and interleukin-10 , 2012, Neuropharmacology.

[171]  R. D'Hooge,et al.  TUDCA, a Bile Acid, Attenuates Amyloid Precursor Protein Processing and Amyloid-β Deposition in APP/PS1 Mice , 2012, Molecular Neurobiology.

[172]  P. Neuvonen,et al.  Gender, but not CYP7A1 or SLCO1B1 polymorphism, affects the fasting plasma concentrations of bile acids in human beings. , 2012, Basic & clinical pharmacology & toxicology.

[173]  P. Deen,et al.  The Succinate Receptor as a Novel Therapeutic Target for Oxidative and Metabolic Stress-Related Conditions , 2012, Front. Endocrin..

[174]  G. Bifulco,et al.  The Bile Acid Receptor GPBAR-1 (TGR5) Modulates Integrity of Intestinal Barrier and Immune Response to Experimental Colitis , 2011, PloS one.

[175]  A. Moschetta,et al.  Bile acids and colon cancer: Solving the puzzle with nuclear receptors. , 2011, Trends in molecular medicine.

[176]  M. Orešič,et al.  Farnesoid X Receptor Deficiency Improves Glucose Homeostasis in Mouse Models of Obesity , 2011, Diabetes.

[177]  S. Kliewer,et al.  FGF15/19 regulates hepatic glucose metabolism by inhibiting the CREB-PGC-1α pathway. , 2011, Cell metabolism.

[178]  J. Auwerx,et al.  The bile acid membrane receptor TGR5 as an emerging target in metabolism and inflammation. , 2011, Journal of hepatology.

[179]  D. Hanahan,et al.  Hallmarks of Cancer: The Next Generation , 2011, Cell.

[180]  P. Siersema,et al.  Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease , 2011, Gut.

[181]  M. Messaoudi,et al.  Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects , 2010, British Journal of Nutrition.

[182]  Marcus J. Claesson,et al.  Composition, variability, and temporal stability of the intestinal microbiota of the elderly , 2010, Proceedings of the National Academy of Sciences.

[183]  M. Cawthorne,et al.  Roles of GPR41 and GPR43 in leptin secretory responses of murine adipocytes to short chain fatty acids , 2010, FEBS letters.

[184]  S. Fiorucci,et al.  Bile-acid-activated receptors: targeting TGR5 and farnesoid-X-receptor in lipid and glucose disorders. , 2009, Trends in pharmacological sciences.

[185]  J. Auwerx,et al.  TGR5-mediated bile acid sensing controls glucose homeostasis. , 2009, Cell metabolism.

[186]  W. R. Wikoff,et al.  Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites , 2009, Proceedings of the National Academy of Sciences.

[187]  Ann M. Thomas,et al.  Farnesoid X Receptor Deficiency in Mice Leads to Increased Intestinal Epithelial Cell Proliferation and Tumor Development , 2009, Journal of Pharmacology and Experimental Therapeutics.

[188]  T. Wiele,et al.  Arabinoxylan‐oligosaccharides (AXOS) affect the protein/carbohydrate fermentation balance and microbial population dynamics of the Simulator of Human Intestinal Microbial Ecosystem , 2008, Microbial biotechnology.

[189]  B. Roe,et al.  A core gut microbiome in obese and lean twins , 2008, Nature.

[190]  A. Moschetta,et al.  Nuclear bile acid receptor FXR protects against intestinal tumorigenesis. , 2008, Cancer research.

[191]  Masashi Yanagisawa,et al.  Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41 , 2008, Proceedings of the National Academy of Sciences.

[192]  Yang Li,et al.  Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids. , 2008, Endocrinology.

[193]  N. Mitro,et al.  The pharmacological exploitation of cholesterol 7alpha-hydroxylase, the key enzyme in bile acid synthesis: from binding resins to chromatin remodelling to reduce plasma cholesterol. , 2007, Pharmacology & therapeutics.

[194]  N. Mitro,et al.  Age‐related changes in bile acid synthesis and hepatic nuclear receptor expression , 2007, European journal of clinical investigation.

[195]  F. Moy,et al.  The nuclear hormone receptor farnesoid X receptor (FXR) is activated by androsterone. , 2006, Endocrinology.

[196]  Folkert Kuipers,et al.  The Farnesoid X Receptor Modulates Adiposity and Peripheral Insulin Sensitivity in Mice* , 2006, Journal of Biological Chemistry.

[197]  Ke Ma,et al.  Farnesoid X receptor is essential for normal glucose homeostasis. , 2006, The Journal of clinical investigation.

[198]  J. Auwerx,et al.  Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation , 2006, Nature.

[199]  Timothy M Willson,et al.  Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[200]  Ki-Choon Choi,et al.  Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. , 2005, Endocrinology.

[201]  Folkert Kuipers,et al.  The Farnesoid X Receptor Modulates Hepatic Carbohydrate Metabolism during the Fasting-Refeeding Transition* , 2005, Journal of Biological Chemistry.

[202]  G. Tsujimoto,et al.  Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. , 2005, Biochemical and biophysical research communications.

[203]  R. Sinha,et al.  Meat consumption and risk of colorectal cancer. , 2005, JAMA.

[204]  S. Joo,et al.  Ursodeoxycholic acid inhibits pro-inflammatory repertoires, IL-1β and nitric oxide in rat microglia , 2003, Archives of pharmacal research.

[205]  Giovanni Galli,et al.  Coordinated Control of Cholesterol Catabolism to Bile Acids and of Gluconeogenesis via a Novel Mechanism of Transcription Regulation Linked to the Fasted-to-fed Cycle* , 2003, Journal of Biological Chemistry.

[206]  Grace Guo,et al.  The Farnesoid X-receptor Is an Essential Regulator of Cholesterol Homeostasis* , 2003, The Journal of Biological Chemistry.

[207]  Ricky W. Johnstone,et al.  Histone-deacetylase inhibitors: novel drugs for the treatment of cancer , 2002, Nature Reviews Drug Discovery.

[208]  H. Clevers,et al.  APC, Signal transduction and genetic instability in colorectal cancer , 2001, Nature Reviews Cancer.

[209]  M. Camilleri Pathophysiology in irritable bowel syndrome. , 2001, Drug news & perspectives.

[210]  J. Dietschy,et al.  Gender‐related differences in bile acid and sterol metabolism in outbred CD‐1 mice fed low‐ and high‐cholesterol diets , 1998, Hepatology.

[211]  Valentino Bontempo,et al.  Branched-chain amino acids. , 2015, Methods in enzymology.

[212]  G. Belforte,et al.  Simulation of the metabolism and enterohepatic circulation of endogenous deoxycholic acid in humans using a physiologic pharmacokinetic model for bile acid metabolism. , 1987, Gastroenterology.

[213]  G. Macfarlane,et al.  Short chain fatty acids in human large intestine, portal, hepatic and venous blood. , 1987, Gut.

[214]  M. M. Fisher,et al.  Sex differences in the bile acid composition of human bile: studies in patients with and without gallstones. , 1973, Canadian Medical Association journal.

[215]  T. Midtvedt,et al.  Metabolism of cholic acid in germfree animals after the establishment in the intestinal tract of deconjugating and 7 alpha-dehydroxylating bacteria. , 2009, Acta pathologica et microbiologica Scandinavica.

[216]  T. Midtvedt,et al.  Bile acid transformations by microbial strains belonging to genera found in intestinal contents. , 1967, Acta pathologica et microbiologica Scandinavica.

[217]  T. Midtvedt,et al.  ISOLATED FECAL MICROORGANISMS CAPABLE OF 7 α-DEHYDROXYLATING BILE ACIDS , 1966, The Journal of experimental medicine.