Gut microbiota-derived metabolites as central regulators in metabolic disorders

Alam, 2018, Role of gut microbiota in intestinal wound healing and barrier function, Tissue Barriers, 6, 1539595, 10.1080/21688370.2018.1539595

Cheng, 2019, Interactions between the gut microbiota and the host innate immune response against pathogens, Front Immunol, 10, 10.3389/fimmu.2019.00607

Sittipo, 2019, Microbial metabolites determine host health and the status of some diseases, Int J Mol Sci, 20, 10.3390/ijms20215296

Ni, 2017, Gut microbiota and IBD: causation or correlation?, Nat Rev Gastroenterol Hepatol, 14, 573, 10.1038/nrgastro.2017.88

Alhinai, 2019, The role of the gut microbiota in colorectal cancer causation, Int J Mol Sci, 20, 10.3390/ijms20215295

Ding, 2019, Revisit gut microbiota and its impact on human health and disease, J Food Drug Anal, 27, 623, 10.1016/j.jfda.2018.12.012

Diehl, 2017, Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis, N Engl J Med, 377, 2063, 10.1056/NEJMra1503519

Dabke, 2019, The gut microbiome and metabolic syndrome, J Clin Invest, 129, 4050, 10.1172/JCI129194

Lamichhane, 2018, Gut metabolome meets microbiome: a methodological perspective to understand the relationship between host and microbe, Methods, 149, 3, 10.1016/j.ymeth.2018.04.029

Tilg, 2020, The intestinal microbiota fuelling metabolic inflammation, Nat Rev Immunol, 20, 40, 10.1038/s41577-019-0198-4

Bäckhed, 2007, Mechanisms underlying the resistance to diet-induced obesity in germ-free mice, Proc Natl Acad Sci U S A, 104, 979, 10.1073/pnas.0605374104

Bäckhed, 2004, The gut microbiota as an environmental factor that regulates fat storage, Proc Natl Acad Sci U S A, 101, 15718, 10.1073/pnas.0407076101

Turnbaugh, 2006, An obesity-associated gut microbiome with increased capacity for energy harvest, Nature, 444, 1027, 10.1038/nature05414

Le Roy, 2013, Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice, Gut, 62, 1787, 10.1136/gutjnl-2012-303816

Ridaura, 2013, Gut microbiota from twins discordant for obesity modulate metabolism in mice, Science, 341, 10.1126/science.1241214

Kimura, 2020, Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice, Science, 367, 10.1126/science.aaw8429

Ley, 2006, Microbial ecology: human gut microbes associated with obesity, Nature, 444, 1022, 10.1038/4441022a

Cotillard, 2013, Dietary intervention impact on gut microbial gene richness, Nature, 500, 585, 10.1038/nature12480

Le Chatelier, 2013, Richness of human gut microbiome correlates with metabolic markers, Nature, 500, 541, 10.1038/nature12506

Aron-Wisnewsky, 2019, Major microbiota dysbiosis in severe obesity: fate after bariatric surgery, Gut, 68, 70, 10.1136/gutjnl-2018-316103

Chassaing, 2017, Colonic microbiota Encroachment correlates with dysglycemia in humans, Cell Mol Gastroenterol Hepatol, 4, 205, 10.1016/j.jcmgh.2017.04.001

de Groot, 2020, Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time, Gut, 69, 502, 10.1136/gutjnl-2019-318320

Kootte, 2017, Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition, Cell Metab, 26, 611, 10.1016/j.cmet.2017.09.008

Yu, 2020, Fecal microbiota transplantation for the improvement of metabolism in obesity: the FMT-TRIM double-blind placebo-controlled pilot trial, PLoS Med, 17, 10.1371/journal.pmed.1003051

Chen, 2019, Metabolome analysis for investigating host-gut microbiota interactions, J Formos Med Assoc, 118(Suppl 1), S10, 10.1016/j.jfma.2018.09.007

Monnerie, 2020, Metabolomic and lipidomic signatures of metabolic syndrome and its physiological components in adults: a systematic review, Sci Rep, 10, 10.1038/s41598-019-56909-7

Liu, 2017, Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention, Nat Med, 23, 859, 10.1038/nm.4358

Pedersen, 2016, Human gut microbes impact host serum metabolome and insulin sensitivity, Nature, 535, 376, 10.1038/nature18646

Fiamoncini, 2018, Plasma metabolome analysis identifies distinct human metabotypes in the postprandial state with different susceptibility to weight loss-mediated metabolic improvements, Faseb J, 32, 5447, 10.1096/fj.201800330R

Surowiec, 2019, Metabolomic and lipidomic assessment of the metabolic syndrome in Dutch middle-aged individuals reveals novel biological signatures separating health and disease, Metabolomics, 15, 23, 10.1007/s11306-019-1484-7

Org, 2017, Relationships between gut microbiota, plasma metabolites, and metabolic syndrome traits in the METSIM cohort, Genome Biol, 18, 10.1186/s13059-017-1194-2

Zhang, 2015, Dietary modulation of gut microbiota contributes to alleviation of both genetic and simple obesity in children, EBioMedicine, 2, 968, 10.1016/j.ebiom.2015.07.007

Koh, 2018, Microbially produced imidazole propionate impairs insulin signaling through mTORC1, Cell, 175, 947, 10.1016/j.cell.2018.09.055

Hoyles, 2018, Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women, Nat Med, 24, 1070, 10.1038/s41591-018-0061-3

Ratajczak, 2019, Immunomodulatory potential of gut microbiome-derived short-chain fatty acids (SCFAs), Acta Biochim Pol, 66, 1

McGlone, 2019, Bile acids and the metabolic syndrome, Ann Clin Biochem, 56, 326, 10.1177/0004563218817798

Thomas, 2008, Targeting bile-acid signalling for metabolic diseases, Nat Rev Drug Discov, 7, 678, 10.1038/nrd2619

Ma, 2014, Bile acids, obesity, and the metabolic syndrome, Best Pract Res Clin Gastroenterol, 28, 573, 10.1016/j.bpg.2014.07.004

Ðanić, 2018, Pharmacological applications of bile acids and their derivatives in the treatment of metabolic syndrome, Front Pharmacol, 9, 10.3389/fphar.2018.01382

Kuno, 2018, Reduction in hepatic secondary bile acids caused by short-term antibiotic-induced dysbiosis decreases mouse serum glucose and triglyceride levels, Sci Rep, 8, 10.1038/s41598-018-19545-1

Duboc, 2013, Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases, Gut, 62, 531, 10.1136/gutjnl-2012-302578

Parséus, 2017, Microbiota-induced obesity requires farnesoid X receptor, Gut, 66, 429, 10.1136/gutjnl-2015-310283

Lambert, 2003, The farnesoid X-receptor is an essential regulator of cholesterol homeostasis, J Biol Chem, 278, 2563, 10.1074/jbc.M209525200

Prawitt, 2011, Farnesoid X receptor deficiency improves glucose homeostasis in mouse models of obesity, Diabetes, 60, 1861, 10.2337/db11-0030

Schmitt, 2015, Protective effects of farnesoid X receptor (FXR) on hepatic lipid accumulation are mediated by hepatic FXR and independent of intestinal FGF15 signal, Liver Int, 35, 1133, 10.1111/liv.12456

Jiang, 2015, Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction, Nat Commun, 6, 10.1038/ncomms10166

Tomlinson, 2002, Transgenic mice expressing human fibroblast growth factor-19 display increased metabolic rate and decreased adiposity, Endocrinology, 143, 1741, 10.1210/endo.143.5.8850

Molinaro, 2018, Role of bile acids in metabolic control, Trends Endocrinol Metab, 29, 31, 10.1016/j.tem.2017.11.002

van Nierop, 2017, Clinical relevance of the bile acid receptor TGR5 in metabolism, Lancet Diabetes Endocrinol, 5, 224, 10.1016/S2213-8587(16)30155-3

Velazquez-Villegas, 2018, TGR5 signalling promotes mitochondrial fission and beige remodelling of white adipose tissue, Nat Commun, 9, 10.1038/s41467-017-02068-0

Raimondi, 2008, Bile acids modulate tight junction structure and barrier function of Caco-2 monolayers via EGFR activation, Am J Physiol Gastrointest Liver Physiol, 294, G906, 10.1152/ajpgi.00043.2007

Suzuki, 2010, Dietary fat and bile juice, but not obesity, are responsible for the increase in small intestinal permeability induced through the suppression of tight junction protein expression in LETO and OLETF rats, Nutr Metab, 7, 19, 10.1186/1743-7075-7-19

Stenman, 2012, High-fat-induced intestinal permeability dysfunction associated with altered fecal bile acids, World J Gastroenterol, 18, 923, 10.3748/wjg.v18.i9.923

Devkota, 2012, Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in IL10-/- mice, Nature, 487, 104, 10.1038/nature11225

Natividad, 2018, Bilophila wadsworthia aggravates high fat diet induced metabolic dysfunctions in mice, Nat Commun, 9, 10.1038/s41467-018-05249-7

Joyce, 2014, Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut, Proc Natl Acad Sci U S A, 111, 7421, 10.1073/pnas.1323599111

Morrison, 2016, Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism, Gut Microbes, 7, 189, 10.1080/19490976.2015.1134082

Kim, 2018, Microbiota or short-chain fatty acids: which regulates diabetes?, Cell Mol Immunol, 15, 88, 10.1038/cmi.2017.57

Chambers, 2015, Control of appetite and energy intake by SCFA: what are the potential underlying mechanisms?, Proc Nutr Soc, 74, 328, 10.1017/S0029665114001657

Hu, 2018, Short-chain fatty acids in control of energy metabolism, Crit Rev Food Sci Nutr, 58, 1243, 10.1080/10408398.2016.1245650

Priyadarshini, 2018, Role of short chain fatty acid receptors in intestinal physiology and pathophysiology, Compr Physiol, 8, 1091, 10.1002/cphy.c170050

Zhao, 2018, Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes, Science, 359, 1151, 10.1126/science.aao5774

Makki, 2018, The impact of dietary fiber on gut microbiota in host health and disease, Cell Host Microbe, 23, 705, 10.1016/j.chom.2018.05.012

De Vadder, 2014, Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits, Cell, 156, 84, 10.1016/j.cell.2013.12.016

Zou, 2018, Fiber-Mediated Nourishment of gut microbiota protects against diet-induced obesity by restoring IL-22-mediated colonic health, Cell Host Microbe, 23, 41, 10.1016/j.chom.2017.11.003

Freeland, 2010, Acute effects of intravenous and rectal acetate on glucagon-like peptide-1, peptide YY, ghrelin, adiponectin and tumour necrosis factor-alpha, Br J Nutr, 103, 460, 10.1017/S0007114509991863

Tajiri, 2018, Branched-chain amino acids in liver diseases, Transl Gastroenterol Hepatol, 3, 47, 10.21037/tgh.2018.07.06

Yoneshiro, 2019, BCAA catabolism in brown fat controls energy homeostasis through SLC25A44, Nature, 572, 614, 10.1038/s41586-019-1503-x

Yang, 2016, Metabolic shifts and structural changes in the gut microbiota upon branched-chain amino acid supplementation in middle-aged mice, Amino Acids, 48, 2731, 10.1007/s00726-016-2308-y

Arany, 2018, Branched chain amino acids in metabolic disease, Curr Diab Rep, 18, 10.1007/s11892-018-1048-7

Zhou, 2019, Targeting BCAA catabolism to treat obesity-associated insulin resistance, Diabetes, 68, 1730, 10.2337/db18-0927

Dehghan, 2020, Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) potentially increases the risk of obesity in adults: an exploratory systematic review and dose-response meta- analysis, Obes Rev, 21, 10.1111/obr.12993

Shan, 2017, Association between microbiota-dependent metabolite trimethylamine-N-oxide and type 2 diabetes, Am J Clin Nutr, 106, 888, 10.3945/ajcn.117.157107

Zhuang, 2019, Gut microbe-generated metabolite trimethylamine N-oxide and the risk of diabetes: a systematic review and dose-response meta-analysis, Obes Rev, 20, 883, 10.1111/obr.12843

Koeth, 2013, Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis, Nat Med, 19, 576, 10.1038/nm.3145

Gregory, 2015, Transmission of atherosclerosis susceptibility with gut microbial transplantation, J Biol Chem, 290, 5647, 10.1074/jbc.M114.618249

Tang, 2013, Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk, N Engl J Med, 368, 1575, 10.1056/NEJMoa1109400

Badawy, 2020, Kynurenine pathway and human systems, Exp Gerontol, 129, 10.1016/j.exger.2019.110770

Comai, 2020, Tryptophan in health and disease, Adv Clin Chem, 95, 165, 10.1016/bs.acc.2019.08.005

Yano, 2015, Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis, Cell, 161, 264, 10.1016/j.cell.2015.02.047

Lavelle, 2020, Gut microbiota-derived metabolites as key actors in inflammatory bowel disease, Nat Rev Gastroenterol Hepatol, 17, 223, 10.1038/s41575-019-0258-z

Agus, 2018, Gut microbiota regulation of tryptophan metabolism in health and disease, Cell Host Microbe, 23, 716, 10.1016/j.chom.2018.05.003

Natividad, 2018, Impaired aryl hydrocarbon receptor ligand production by the gut microbiota is a key factor in metabolic syndrome, Cell Metab, 28, 737, 10.1016/j.cmet.2018.07.001

Taleb, 2019, Tryptophan dietary impacts gut barrier and metabolic diseases, Front Immunol, 10, 10.3389/fimmu.2019.02113

Beaumont, 2018, The gut microbiota metabolite indole alleviates liver inflammation in mice, Faseb J, 6681, 10.1096/fj.201800544

Postal, 2020, AhR activation defends gut barrier integrity against damage occurring in obesity, Mol Metab, 39, 101007, 10.1016/j.molmet.2020.101007

Mallmann, 2018, Dysregulation of tryptophan catabolism in metabolic syndrome, Metab Syndr Relat Disord, 16, 135, 10.1089/met.2017.0097

Moyer, 2016, Inhibition of the aryl hydrocarbon receptor prevents Western diet-induced obesity. model for AhR activation by kynurenine via oxidized-LDL, TLR2/4, TGFβ, and IDO1, Toxicol Appl Pharmacol, 300, 13, 10.1016/j.taap.2016.03.011

Laurans, 2018, Genetic deficiency of indoleamine 2,3-dioxygenase promotes gut microbiota-mediated metabolic health, Nat Med, 24, 1113, 10.1038/s41591-018-0060-4

Liu, 2019, Emerging role for kynurenines in metabolic pathologies, Curr Opin Clin Nutr Metab Care, 22, 82, 10.1097/MCO.0000000000000529

Galligan, 2018, Beneficial actions of microbiota-derived tryptophan metabolites, Neurogastroenterol Motil, 30, e13283, 10.1111/nmo.13283

Young, 2015, Gut serotonin is a regulator of obesity and metabolism, Gastroenterology, 149, 253, 10.1053/j.gastro.2015.05.020

Crane, 2015, Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis, Nat Med, 21, 166, 10.1038/nm.3766

Fukui, 2012, High plasma 5-hydroxyindole-3-acetic acid concentrations in subjects with metabolic syndrome, Diabetes Care, 35, 163, 10.2337/dc11-1619

Molinaro, 2020, Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology, Nat Commun, 11, 10.1038/s41467-020-19589-w

Allegretti, 2020, Effects of fecal microbiota transplantation with oral capsules in obese patients, Clin Gastroenterol Hepatol, 18, 855, 10.1016/j.cgh.2019.07.006

Dao, 2016, Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology, Gut, 65, 426, 10.1136/gutjnl-2014-308778

Zhang, 2019, Akkermansia muciniphila is a promising probiotic, Microb Biotechnol, 12, 1109, 10.1111/1751-7915.13410

Depommier, 2019, Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study, Nat Med, 25, 1096, 10.1038/s41591-019-0495-2

Bian, 2019, Administration of Akkermansia muciniphila ameliorates dextran sulfate sodium-induced ulcerative colitis in mice, Front Microbiol, 10, 10.3389/fmicb.2019.02259

Wu, 2020, An Akkermansia muciniphila subtype alleviates high-fat diet-induced metabolic disorders and inhibits the neurodegenerative process in mice, Anaerobe, 61, 10.1016/j.anaerobe.2019.102138

Lazarević, 2019, Semisynthetic bile acids: a new therapeutic option for metabolic syndrome, Pharmacol Res, 146, 104333, 10.1016/j.phrs.2019.104333

Ratziu, 2019, Regenerate: design of a pivotal, randomised, phase 3 study evaluating the safety and efficacy of obeticholic acid in patients with fibrosis due to nonalcoholic steatohepatitis, Contemp Clin Trials, 84, 10.1016/j.cct.2019.06.017

Zhang, 2006, Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice, Proc Natl Acad Sci U S A, 103, 1006, 10.1073/pnas.0506982103

Cao, 2019, FXR agonist GW4064 improves liver and intestinal pathology and alters bile acid metabolism in rats undergoing small intestinal resection, Am J Physiol Gastrointest Liver Physiol, 317, G108, 10.1152/ajpgi.00356.2017

Pathak, 2018, Intestine farnesoid X receptor agonist and the gut microbiota activate G-protein bile acid receptor-1 signaling to improve metabolism, Hepatology, 68, 1574, 10.1002/hep.29857

Huang, 2019, TGR5 agonist ameliorates insulin resistance in the skeletal muscles and improves glucose homeostasis in diabetic mice, Metabolism, 99, 45, 10.1016/j.metabol.2019.07.003

Chambers, 2019, Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial, Gut, 68, 1430, 10.1136/gutjnl-2019-318424

den Besten, 2015, Short-Chain fatty acids protect against high-fat diet-induced obesity via a PPARγ-dependent switch from lipogenesis to fat oxidation, Diabetes, 64, 2398, 10.2337/db14-1213

Fang, 2019, Supplementation with sodium butyrate modulates the composition of the gut microbiota and ameliorates high-fat diet-induced obesity in mice, J Nutr, 149, 747, 10.1093/jn/nxy324

Nagasumi, 2009, Overexpression of GPR40 in pancreatic beta-cells augments glucose-stimulated insulin secretion and improves glucose tolerance in normal and diabetic mice, Diabetes, 58, 1067, 10.2337/db08-1233

Schmidt, 2011, Selective orthosteric free fatty acid receptor 2 (FFA2) agonists: identification of the structural and chemical requirements for selective activation of FFA2 versus FFA3, J Biol Chem, 286, 10628, 10.1074/jbc.M110.210872

Hudson, 2013, Defining the molecular basis for the first potent and selective orthosteric agonists of the FFA2 free fatty acid receptor, J Biol Chem, 288, 17296, 10.1074/jbc.M113.455337

Milligan, 2017, FFA4/GPR120: pharmacology and therapeutic opportunities, Trends Pharmacol Sci, 38, 809, 10.1016/j.tips.2017.06.006

Cummings, 2018, Restoration of metabolic health by decreased consumption of branched-chain amino acids, J Physiol, 596, 623, 10.1113/JP275075

Luo, 2018, Assessment of serum bile acid profiles as biomarkers of liver injury and liver disease in humans, PLoS One, 13, 10.1371/journal.pone.0193824

Ma, 2019, Serum metabolome and targeted bile acid profiling reveals potential novel biomarkers for drug-induced liver injury, Medicine, 98, 10.1097/MD.0000000000016717