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Protein & Cell

ISSN 1674-800X

ISSN 1674-8018(Online)

CN 11-5886/Q

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2018 Impact Factor: 7.575

Protein Cell    2021, Vol. 12 Issue (5) : 360-373    https://doi.org/10.1007/s13238-020-00814-7
REVIEW
The role of the gut microbiome and its metabolites in metabolic diseases
Jiayu Wu1,2,3, Kai Wang1,2,3, Xuemei Wang1,2,3, Yanli Pang1, Changtao Jiang1,2,3()
1. Department of Obstetrics and Gynecology, Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, Third Hospital, Peking University, Beijing 100191, China
2. Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China
3. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, China
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Abstract

It is well known that an unhealthy lifestyle is a major risk factor for metabolic diseases, while in recent years, accumulating evidence has demonstrated that the gut microbiome and its metabolites also play a crucial role in the onset and development of many metabolic diseases, including obesity, type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular disease and so on. Numerous microorganisms dwell in the gastrointestinal tract, which is a key interface for energy acquisition and can metabolize dietary nutrients into many bioactive substances, thus acting as a link between the gut microbiome and its host. The gut microbiome is shaped by host genetics, immune responses and dietary factors. The metabolic and immune potential of the gut microbiome determines its significance in host health and diseases. Therefore, targeting the gut microbiome and relevant metabolic pathways would be effective therapeutic treatments for many metabolic diseases in the near future. This review will summarize information about the role of the gut microbiome in organism metabolism and the relationship between gut microbiome-derived metabolites and the pathogenesis of many metabolic diseases. Furthermore, recent advances in improving metabolic diseases by regulating the gut microbiome will be discussed.

Keywords gut microbiome      metabolism      metabolite      immune regulation      metabolic diseases     
Corresponding Author(s): Changtao Jiang   
Online First Date: 04 February 2021    Issue Date: 08 June 2021
 Cite this article:   
Jiayu Wu,Kai Wang,Xuemei Wang, et al. The role of the gut microbiome and its metabolites in metabolic diseases[J]. Protein Cell, 2021, 12(5): 360-373.
 URL:  
https://academic.hep.com.cn/pac/EN/10.1007/s13238-020-00814-7
https://academic.hep.com.cn/pac/EN/Y2021/V12/I5/360
1 VL Albaugh, B Banan, J Antoun, Y Xiong, Y Guo, J Ping, M Alikhan, BA Clements, NN Abumrad, CR Flynn (2019) Role of bile acids and GLP-1 in mediating the metabolic improvements of bariatric surgery. Gastroenterology 156:1041–1051.e1044
https://doi.org/10.1053/j.gastro.2018.11.017
2 LG Albenberg, GD Wu (2014) Diet and the intestinal microbiome: associations, functions, and implications for health and disease. Gastroenterology 146:1564–1572
https://doi.org/10.1053/j.gastro.2014.01.058
3 SH Al-Lahham, H Roelofsen, M Priebe, D Weening, M Dijkstra, A Hoek, F Rezaee, K Venema, RJ Vonk (2010) Regulation of adipokine production in human adipose tissue by propionic acid. Eur J Clin Invest 40:401–407
https://doi.org/10.1111/j.1365-2362.2010.02278.x
4 J Aron-Wisnewsky, M Warmbrunn, M Nieuwdorp, K Clement (2020) Nonalcoholic fatty liver disease: modulating gut microbiota to improve severity? Gastroenterology 158:1881
https://doi.org/10.1053/j.gastro.2020.01.049
5 CC Bain, V Cerovic (2020) Interactions of the microbiota with the mucosal immune system. Immunology 159:1–3
https://doi.org/10.1111/imm.13159
6 PV Bauere, FA Duca, TMZ Waise, BA Rasmussen, MA Abraham, HJ Dranse, A Puri, CA O’Brien, TKT Lam (2018) Metformin alters upper small intestinal microbiota that impact a glucose-SGLT1-sensing glucoregulatory pathway. Cell Metab 27:101–117
https://doi.org/10.1016/j.cmet.2017.09.019
7 S Brandhorst, VD Longo (2019) Dietary restrictions and nutrition in the prevention and treatment of cardiovascular disease. Circ Res 124:952–965
https://doi.org/10.1161/CIRCRESAHA.118.313352
8 EE Canfora, RCR Meex, K Venema, EE Blaak (2019) Gut microbial metabolites in obesity, NAFLD and T2DM. Nat Rev Endocrinol 15:261–273
https://doi.org/10.1038/s41574-019-0156-z
9 PV Chang, L Hao, S Offermanns, R Medzhitov (2014) The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci USA 111:2247–2252
https://doi.org/10.1073/pnas.1322269111
10 E Corpeleijn, WH Saris, EE Blaak (2009) Metabolic flexibility in the development of insulin resistance and type 2 diabetes: effects of lifestyle. Obes Rev 10:178–193
https://doi.org/10.1111/j.1467-789X.2008.00544.x
11 JH Cummings, EW Pomare, WJ Branch, CP Naylor, GT Macfarlane (1987) Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 28:1221–1227
https://doi.org/10.1136/gut.28.10.1221
12 R da Cabo, MP Mattson (2019) Effects of intermittent fasting on health, aging, and disease. N Engl J Med 381:2541–2551
https://doi.org/10.1056/NEJMra1905136
13 HE Da Silva, A Teterina, EM Comelli, A Taibi, BM Arendt, SE Fischer, W Lou, JP Allard (2018) Nonalcoholic fatty liver disease is associated with dysbiosis independent of body mass index and insulin resistance. Sci Rep 8:1466
https://doi.org/10.1038/s41598-018-19753-9
14 LA David, CF Maurice, RN Carmody, DB Gootenberg, JE Button, BE Wolfe, AV Ling, AS Devlin, Y Varma, MA Fischbachet al. (2014) Diet rapidly and reproducibly alters the human gut microbiome. Nature 505:559–563
https://doi.org/10.1038/nature12820
15 F de Vegt, JM Dekker, A Jager, E Hienkens, PJ Kostense, CD Stehouwer, G Nijpels, LM Bouter, RJ Heine (2001) Relation of impaired fasting and postload glucose with incident type 2 diabetes in a Dutch population: the Hoorn Study. JAMA 285:2109–2113
https://doi.org/10.1001/jama.285.16.2109
16 A Di Francesco, C Di Germanio, M Bernier, R de Cabo (2018) A time to fast. Science 362:770–775
https://doi.org/10.1126/science.aau2095
17 H Duboc, Y Taché, AF Hofmann (2014) The bile acid TGR5 membrane receptor: from basic research to clinical application. Dig Liver Dis 46:302–312
https://doi.org/10.1016/j.dld.2013.10.021
18 EA Eloe-Fadrosh, A Brady, J Crabtree, EF Drabek, B Ma, A Mahurkar, J Ravel, M Haverkamp, AM Fiorino, C Botelhoet al. (2015) Functional dynamics of the gut microbiome in elderly people during probiotic consumption. mBio 6:e00231
https://doi.org/10.1128/mBio.00231-15
19 K Enck, S Banks, H Yadav, ME Welker, EC Opara (2020) Development of a novel oral delivery vehicle for probiotics. Curr Pharm Des 26:3134
https://doi.org/10.2174/1381612826666200210111925
20 C Ferrario, V Taverniti, C Milani, W Fiore, M Laureati, I De Noni, M Stuknyte, B Chouaia, P Riso, S Guglielmetti (2014) Modulation of fecal clostridiales bacteria and butyrate by probiotic intervention with Lactobacillus paracasei DG varies among healthy adults. J Nutr 144:1787–1796
https://doi.org/10.3945/jn.114.197723
21 K Forslund, F Hidebrand, T Nielsen, G Falony, E Le Chatelier, S Sunagawa, E Prifti, S Vieira-Silva, V Gudmundsdottri, KH Pedersenet al. (2015) Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528:262–266
https://doi.org/10.1038/nature15766
22 G Frost, ML Sleeth, M Sahuri-Arisoylu, B Lizarbe, S Cerdan, L Brody, J Anastasovska, S Ghourab, M Hankir, S Zhanget al. (2014) The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat Commun 5:3611
https://doi.org/10.1038/ncomms4611
23 T Fu, S Coulter, E Yoshihara, TG Oh, S Fang, F Cayabyab, QY Zhu, T Zhang, M Lelanc, SH Liuet al. (2019) FXR regulates intestinal cancer stem cell proliferation. Cell 176:1098–1112
https://doi.org/10.1016/j.cell.2019.01.036
24 M Funabashi, TL Grove, M Wang, Y Varma, ME McFadden, LC Brown, C Guo, S Higginbottom, SC Almo, MA Fischbach (2020) A metabolic pathway for bile acid dehydroxylation by the gut microbiome. Nature 582:566–570
https://doi.org/10.1038/s41586-020-2396-4
25 GR Gibson, R Hutkins, ME Sanders, SL Prescott, RA Reimer, SJ Salminen, K Scott, C Stanton, KS Swanson, PD Caniet al. (2017) Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev 14:491–502
https://doi.org/10.1038/nrgastro.2017.75
26 JA Gilbert, MJ Blaser, JG Caporaso, JK Jansson, SV Lynch, R Knight (2018) Current understanding of the human microbiome. Nat Med 24:392–400
https://doi.org/10.1038/nm.4517
27 SM Grundy (2012) Pre-diabetes, metabolic syndrome, and cardiovascular risk. J Am Coll Cardiol 59:635–643
https://doi.org/10.1016/j.jacc.2011.08.080
28 Y Gu, X Wang, J Li, Y Zhang, H Zhong, R Liu, D Zhang, Q Feng, X Xie, J Honget al. (2017) Analyses of gut microbiota and plasma bile acids enable stratification of patients for antidiabetic treatment. Nat Commun 8:1785
https://doi.org/10.1038/s41467-017-01682-2
29 Y Guo, Y Qi, X Yang, L Zhao, S Wen, Y Liu, L Tang (2016) Association between polycystic ovary syndrome and gut microbiota. PLoS ONE 11:e0153196
https://doi.org/10.1371/journal.pone.0153196
30 CJ Guo, BM Allen, KJ Hiam, D Dodd, W Van Treuren, S Higginbottom, K Nagashima, CR Fischer, JL Sonnenburg, MH Spitzeret al. (2019) Depletion of microbiome-derived molecules in the host using Clostridium genetics. Science 366:1282
https://doi.org/10.1126/science.aav1282
31 S Hang, D Paik, L Yao, E Kim, J Trinath, J Lu, S Ha, BN Nelson, SP Kelly, L Wuet al. (2019) Bile acid metabolites control T(H)17 and T(reg) cell differentiation. Nature 576:143–148
https://doi.org/10.1038/s41586-019-1785-z
32 M Hatori, C Vollmers, A Zarrinpar, L DiTacchio, EA Bushong, S Gill, M Leblanc, A Chaix, M Joens, JAJ Fitzpatrick (2012) Timerestricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab 15:848–860
https://doi.org/10.1016/j.cmet.2012.04.019
33 SB Heymsfield, TA Wadden (2017) Mechanisms, pathophysiology, and management of obesity. Engl J Med 376:254–266
https://doi.org/10.1056/NEJMra1514009
34 FJ Huang, XJ Zheng, XH Ma, RQ Jiang, WY Zhou, SP Zhou, YJ Zhang, S Lei, SL Wang, JL Kuanget al. (2019) Theabrownin from Puerh tea attenuates hypercholesterolemia via modulation of gut microbiota and bile acid metabolism. Nat Commun 10:4971
https://doi.org/10.1038/s41467-019-12896-x
35 ZR Huang, JC Deng, QY Li, YJ Cao, YC Lin, WD Bai, B Liu, PF Rao, L Ni, XC Lv (2020) Protective Mechanism of Common Buckwheat (Fagopyrum esculentum Moench.) against nonalcoholic fatty liver disease associated with dyslipidemia in mice fed a high-fat and high-cholesterol diet. J Agric Food Chem 68:6530–6543
https://doi.org/10.1021/acs.jafc.9b08211
36 KB Islam, S Fukiya, M Hagio, N Fujii, S Ishizuka, T Ooka, Y Ogura, T Hayashi, A Yokota (2011) Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology 141:1773–1781
https://doi.org/10.1053/j.gastro.2011.07.046
37 SM Jandhyala, R Talukdar, C Subramanyam, H Vuyyuru, M Sasikala, D Nageshwar Reddy (2015) Role of the normal gut microbiota. World J Gastroenterol 21:8787–8803
https://doi.org/10.3748/wjg.v21.i29.8787
38 C Jiang, C Xie, Y Lv, J Li, KW Krausz, J Shi, CN Brocker, D Desai, SG Amin, WH Bissonet al. (2015) Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction. Nat Commun 6:10166
https://doi.org/10.1038/ncomms10166
39 M Kars, L Yang, MF Gregor, BS Mohammed, TA Pietka, BN Finck, BW Patterson, JD Horton, B Mittendorfer, GS Hotamisligilet al. (2010) Tauroursodeoxycholic acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women. Diabetes 59:1899–1905
https://doi.org/10.2337/db10-0308
40 ST Kelley, DV Skarra, AJ Rivera, VG Thackray (2016) The gut microbiome is altered in a letrozole-induced mouse model of polycystic ovary syndrome. PLoS ONE 11:e0146509
https://doi.org/10.1371/journal.pone.0146509
41 DM Kim (2015) Gut microbiota-mediated drug-antibiotic interactions. Drug Metab Dispos 43:1581–1589
https://doi.org/10.1124/dmd.115.063867
42 WC Knowler, E Barrett-Connor, SE Fowler, RF Hamman, JM Lachin, EA Walker, DM Nathan (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393–403
https://doi.org/10.1056/NEJMoa012512
43 P Kovatcheva-Datchary, A Nilsson, R Akrami, YS Lee, F De Vadder, T Arora, A Hallen, E Martens, I Bjorck, F Backhed (2015) Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of prevotella. Cell Metab 22:971–982
https://doi.org/10.1016/j.cmet.2015.10.001
44 NB Kristensen, T Bryrup, KH Allin, T Nielsen, TH Hansen, O Pedersen (2016) Alterations in fecal microbiota composition by probiotic supplementation in healthy adults: a systematic review of randomized controlled trials. Genome Med 8:52
https://doi.org/10.1186/s13073-016-0300-5
45 P Larraufie, C Martin-Gallausiaux, N Lapaque, J Dore, FM Gribble, F Reimann, HM Blottiere (2018) SCFAs strongly stimulate PYY production in human enteroendocrine cells. Sci Rep 8:74
https://doi.org/10.1038/s41598-017-18259-0
46 H Larsson, F Lindgärde, G Berglund, B Ahrén (2000) Prediction of diabetes using ADA or WHO criteria in post-menopausal women: a 10-year follow-up study. Diabetologia 43:1224–1228
https://doi.org/10.1007/s001250051516
47 MF Laursen, RP Laursen, A Larnkjær, KF Michaelsen, MI Bahl, TR Licht (2017) Administration of two probiotic strains during early childhood does not affect the endogenous gut microbiota composition despite probiotic proliferation. BMC Microbiol.
https://doi.org/10.1186/s12866-017-1090-7
48 T Le Roy, M Llopis, P Lepage, A Bruneau, S Rabot, C Bevilacqua, P Martin, C Philippe, F Walker, A Badoet al. (2013) Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice. Gut 62:1787–1794
https://doi.org/10.1136/gutjnl-2012-303816
49 M Levy, CA Thaiss, D Zeevi, L Dohnalova, G Zilberman-Schapira, JA Mahdi, E David, A Savidor, T Korem, Y Herziget al. (2015) Microbiota-modulated metabolites shape the intestinal microenvironment by regulating NLRP6 inflammasome signaling. Cell 163:1428–1443
https://doi.org/10.1016/j.cell.2015.10.048
50 GL Li, C Xie, SY Lu, RG Nichols, Y Tian, LC Li, D Patel, YY Ma, CN Brocker, TT Yanet al. (2017) Intermittent fasting promotes white adipose browning and decreases obesity by shaping the gut microbiota. Cell Metab 26:672–685
https://doi.org/10.1016/j.cmet.2017.08.019
51 Z Li, CX Yi, S Katiraei, S Kooijman, E Zhou, CK Chung, Y Gao, JK van den Heuvel, OC Meijer, JFP Berbeeet al. (2018) Butyrate reduces appetite and activates brown adipose tissue via the gutbrain neural circuit. Gut 67:1269–1279
https://doi.org/10.1136/gutjnl-2017-314050
52 PS Lim, CF Loke, YW Ho, HY Tan (2020) Cholesterol homeostasis associated with probiotic supplementation in vivo. J Appl Microbiol
https://doi.org/10.1111/jam.14678
53 L Lindheim, M Bashir, J Munzker, C Trummer, V Zachhuber, B Leber, A Horvath, TR Pieber, G Gorkiewicz, V Stadlbaueret al. (2017) Alterations in gut microbiome composition and barrier function are associated with reproductive and metabolic defects in women with polycystic ovary syndrome (PCOS): a pilot study. PLoS ONE 12:e0168390
https://doi.org/10.1371/journal.pone.0168390
54 R Liu, J Hong, X Xu, Q Feng, D Zhang, Y Gu, J Shi, S Zhao, W Liu, X Wanget al. (2017a) Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention. Nat Med 23:859–868
https://doi.org/10.1038/nm.4358
55 R Liu, C Zhang, Y Shi, F Zhang, L Li, X Wang, Y Ling, H Fu, W Dong, J Shenet al. (2017b) Dysbiosis of gut microbiota associated with clinical parameters in polycystic ovary syndrome. Front Microbiol 8:324
https://doi.org/10.3389/fmicb.2017.00324
56 VD Longo, S Panda (2016) Fasting, circadian rhythms, and timerestricted feeding in healthy lifespan. Cell Metab 23:1048–1059
https://doi.org/10.1016/j.cmet.2016.06.001
57 P Louis, GL Hold, HJ Flint (2014) The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol 12:661–672
https://doi.org/10.1038/nrmicro3344
58 M Manco, L Putignani, GF Bottazzo (2010) Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk. Endocr Rev 31:817–844
https://doi.org/10.1210/er.2009-0030
59 K Mao, AP Baptista, S Tamoutounour, L Zhuang, N Bouladoux, AJ Martins, Y Huang, MY Gerner, Y Belkaid, RN Germain (2018) Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism. Nature 554:255–259
https://doi.org/10.1038/nature25437
60 T Matsubara, F Li, FJ Gonzalez (2013) FXR signaling in the enterohepatic system. Mol Cell Endocrinol 368:17–29
https://doi.org/10.1016/j.mce.2012.05.004
61 V Meslier, M Laiola, HM Roager, F De Filippis, H Roume, B Quinquis, R Giacco, I Mennella, R Ferracane, N Ponset al. (2020) Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake. Gut 69:1258–1268
https://doi.org/10.1136/gutjnl-2019-320438
62 J Miyamoto, M Igarashi, K Watanabe, SI Karaki, H Mukouyama, S Kishino, X Li, A Ichimura, J Irie, Y Sugimotoet al. (2019) Gut microbiota confers host resistance to obesity by metabolizing dietary polyunsaturated fatty acids. Nat Commun 10:4007
https://doi.org/10.1038/s41467-019-11978-0
63 DM Nathan, MB Davidson, RA DeFronzo, RJ Heine, RR Henry, R Pratley, B Zinman, A American Diabetes (2007) Impaired fasting glucose and impaired glucose tolerance: implications for care. Diabetes Care 30:753–759
https://doi.org/10.2337/dc07-9920
64 RJ Norman, D Dewailly, RS Legro, TE Hickey (2007) Polycystic ovary syndrome. The Lancet 370:685–697
https://doi.org/10.1016/S0140-6736(07)61345-2
65 ME Perez-Munoz, MC Arrieta, AE Ramer-Tait, J Walter (2017) A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Microbiome 5:48
https://doi.org/10.1186/s40168-017-0268-4
66 Y Pi, C Mu, K Gao, Z Liu, Y Peng, W Zhu (2020) Increasing the hindgut carbohydrate/protein ratio by cecal infusion of corn starch or casein hydrolysate drives gut microbiota-related bile acid metabolism to stimulate colonic barrier function. mSystems 5: e00176–20
https://doi.org/10.1128/mSystems.00176-20
67 BM Popkin, LS Adair, SW Ng (2012) Global nutrition transition and the pandemic of obesity in developing countries. Nutr Rev 70:3–21
https://doi.org/10.1111/j.1753-4887.2011.00456.x
68 A Psichas, ML Sleeth, KG Murphy, L Brooks, GA Bewick, AC Hanyaloglu, MA Ghatei, SR Bloom, G Frost (2015) The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int J Obes (Lond) 39:424–429
https://doi.org/10.1038/ijo.2014.153
69 X Qi, C Yun, L Sun, J Xia, Q Wu, Y Wang, L Wang, Y Zhang, X Liang, L Wanget al. (2019) Gut microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome. Nat Med 25:1225–1233
https://doi.org/10.1038/s41591-019-0509-0
70 RA Quinn, AV Melnik, A Vrbanac, T Fu, KA Patras, MP Christy, Z Bodai, P Belda-Ferre, A Tripathi, LK Chunget al. (2020) Global chemical effects of the microbiome include new bile-acid conjugations. Nature 579:123–129
https://doi.org/10.1038/s41586-020-2047-9
71 SW Ragsdale, E Pierce (2008) Acetogenesis and the Wood-Ljungdahl pathway of CO(2) fixation. Biochem Biophys Acta 1784:1873–1898
https://doi.org/10.1196/annals.1419.015
72 RK Rao, A Seth, P Sheth (2004) Recent advances in alcoholic liver disease I. Role of intestinal permeability and endotoxemia in alcoholic liver disease. Am J Physiol Gastrointest Liver Physiol 286:G881–G884
https://doi.org/10.1152/ajpgi.00006.2004
73 SM Reilly, AR Saltiel (2017) Adapting to obesity with adipose tissue inflammation. Nat Rev Endocrinol 13:633–643
https://doi.org/10.1038/nrendo.2017.90
74 LA Rubio, I Aranda-Olmedo, M Martín-Pedrosa (2020) Inclusion of limited amounts of extruded legumes plus cereal mixes in normocaloric or obesogenic diets for rats: effects on lipid profile. Foods (Basel, Switzerland)9
https://doi.org/10.3390/foods9060704
75 S Sanna, NR van Zuydam, A Mahajan, A Kurilshikov, A Vich Vila, U Võsa, Z Mujagic, AAM Masclee, D Jonkers, M Oostinget al. (2019) Causal relationships among the gut microbiome, shortchain fatty acids and metabolic diseases. Nat Genet 51:600–605
https://doi.org/10.1038/s41588-019-0350-x
76 PL Santaguida, C Balion, D Hunt, K Morrison, H Gerstein, P Raina, L Booker, H Yazdi (2005) Diagnosis, prognosis, and treatment of impaired glucose tolerance and impaired fasting glucose. Evidence report/technology assessment (Summary), 1–11
77 BO Schroeder, F Backhed (2016) Signals from the gut microbiota to distant organs in physiology and disease. Nat Med 22:1079–1089
https://doi.org/10.1038/nm.4185
78 JB Schwimmer, JS Johnson, JE Angeles, C Behling, PH Belt, I Borecki, C Bross, J Durelle, NP Goyal, G Hamiltonet al. (2019) Microbiome signatures associated with steatohepatitis and moderate to severe fibrosis in children with nonalcoholic fatty liver disease. Gastroenterology 157:1109–1122
https://doi.org/10.1053/j.gastro.2019.06.028
79 R Sender, S Fuchs, R Milo (2016) Are we really vastly outnumbered? revisiting the ratio of bacterial to host cells in humans. Cell 164:337–340
https://doi.org/10.1016/j.cell.2016.01.013
80 JE Shaw, PZ Zimmet, M de Courten, GK Dowse, P Chitson, H Gareeboo, F Hemraj, D Fareed, J Tuomilehto, KG Alberti (1999) Impaired fasting glucose or impaired glucose tolerance. What best predicts future diabetes in Mauritius? Diabetes Care 22:399–402
https://doi.org/10.2337/diacare.22.3.399
81 X Song, X Sun, SF Oh, M Wu, Y Zhang, W Zheng, N Geva-Zatorsky, R Jupp, D Mathis, C Benoistet al. (2020) Microbial bile acid metabolites modulate gut RORγ(+) regulatory Tcell homeostasis. Nature 577:410–415
https://doi.org/10.1038/s41586-019-1865-0
82 J Sun, NJ Buys (2016) Glucose- and glycaemic factor-lowering effects of probiotics on diabetes: a meta-analysis of randomised placebo-controlled trials. Br J Nutr 115:1167–1177
https://doi.org/10.1017/S0007114516000076
83 L Sun, C Xie, G Wang, Y Wu, Q Wu, X Wang, J Liu, Y Deng, J Xia, B Chenet al. (2018) Gut microbiota and intestinal FXR mediate the clinical benefits of metformin. Nat Med 24:1919–1929
https://doi.org/10.1038/s41591-018-0222-4
84 L Sun, Y Pang, X Wang, Q Wu, H Liu, B Liu, G Liu, M Ye, W Kong, C Jiang (2019) Ablation of gut microbiota alleviates obesityinduced hepatic steatosis and glucose intolerance by modulating bile acid metabolism in hamsters. Acta Pharm Sin B 9:702–710
https://doi.org/10.1016/j.apsb.2019.02.004
85 EF Sutton, R Beyl, KS Early, WT Cefalu, E Ravussin, CM Peterson (2018) Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes. Cell Metab 27:1212–1221
https://doi.org/10.1016/j.cmet.2018.04.010
86 JR Swann, EJ Want, FM Geier, K Spagou, ID Wilson, JE Sidaway, JK Nicholson, E Holmes (2011) Systemic gut microbial modulation of bile acid metabolism in host tissue compartments. Proc Natl Acad Sci USA 108(Suppl 1):4523–4530
https://doi.org/10.1073/pnas.1006734107
87 LB Thingholm, MC Ruhlemann, M Koch, B Fuqua, G Laucke, R Boehm, C Bang, EA Franzosa, M Hubenthal, A Rahnavardet al. (2019) Obese Individuals with and without Type 2 diabetes show different gut microbial functional capacity and composition. Cell Host Microbe 26(252–264):e210
https://doi.org/10.1016/j.chom.2019.07.004
88 G Tolhurst, H Heffron, YS Lam, HE Parker, AM Habib, E Diakogiannaki, J Cameron, J Grosse, F Reimann, FM Gribble (2012) Shortchain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 61:364–371
https://doi.org/10.2337/db11-1019
89 MS Trabelsi, M Daoudi, J Prawitt, S Ducastel, V Touche, SI Sayin, A Perino, CA Brighton, Y Sebti, J Kluzaet al. (2015) Farnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells. Nat Commun 6:7629
https://doi.org/10.1038/ncomms8629
90 J Tuomilehto, J Lindström, JG Eriksson, TT Valle, H Hämäläinen, P Ilanne-Parikka, S Keinänen-Kiukaanniemi, M Laakso, A Louheranta, M Rastaset al. (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344:1343–1350
https://doi.org/10.1056/NEJM200105033441801
91 PJ Turnbaugh, RE Ley, MA Mahowald, V Magrini, ER Mardis, JI Gordon (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444:1027–1031
https://doi.org/10.1038/nature05414
92 PJ Turnbaugh, F Backhed, L Fulton, JI Gordon (2008) Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3:213–223
https://doi.org/10.1016/j.chom.2008.02.015
93 M Usami, K Kishimoto, A Ohata, M Miyoshi, M Aoyama, Y Fueda, J Kotani (2008) Butyrate and trichostatin A attenuate nuclear factor kappaB activation and tumor necrosis factor alpha secretion and increase prostaglandin E2 secretion in human peripheral blood mononuclear cells. Nutr Res 28:321–328
https://doi.org/10.1016/j.nutres.2008.02.012
94 F Vendrame, PA Gottlieb (2004) Prediabetes: prediction and prevention trials. Endocrinol Metab Clin N Am 33(75–92):ix
https://doi.org/10.1016/j.ecl.2003.12.006
95 P Vernocchi, F Del Chierico, L Putignani (2016) Gut microbiota profiling: metabolomics based approach to unravel compounds affecting human health. Front Microbiol 7:1144
https://doi.org/10.3389/fmicb.2016.01144
96 SS Virani, A Alonso, EJ Benjamin, MS Bittencourt, CW Callaway, AP Carson, AM Chamberlain, AR Chang, S Cheng, FN Dellinget al. (2020) Heart Disease and Stroke Statistics-2020 update: a report from the American Heart Association. Circulation 141: e139–e596
https://doi.org/10.1161/CIR.0000000000000757
97 C Wang, S Nagata, T Asahara, N Yuki, K Matsuda, H Tsuji, T Takahashi, K Nomoto, Y Yamashiro (2015) Intestinal microbiota profiles of healthy pre-school and school-age children and effects of probiotic supplementation. Ann Nutr Metab 67:257–266
https://doi.org/10.1159/000441066
98 B Wang, X Jiang, M Cao, J Ge, Q Bao, L Tang, Y Chen, L Li (2016) Altered fecal microbiota correlates with liver biochemistry in nonobese patients with non-alcoholic fatty liver disease. Sci Rep 6:32002
https://doi.org/10.1038/srep32002
99 L Wang, B Ren, Q Zhang, C Chu, Z Zhao, J Wu, W Zhao, Z Liu, X Liu (2020) Methionine restriction alleviates high-fat diet-induced obesity: involvement of diurnal metabolism of lipids and bile acids. Biochim Biophys Acta 1866:165908
https://doi.org/10.1016/j.bbadis.2020.165908
100 A Whang, R Nagpal, H Yadav (2019) Bi-directional drug-microbiome interactions of anti-diabetics. EbioMedicine 39:591–602
https://doi.org/10.1016/j.ebiom.2018.11.046
101 WB Whitman, DC Coleman, WJ Wiebe (1998) Prokaryotes: the unseen majority. Proc Natl Acad Sci USA 95:6578–6583
https://doi.org/10.1073/pnas.95.12.6578
102 A Worthmann, C John, MC Ruhlemann, M Baguhl, FA Heinsen, N Schaltenberg, M Heine, C Schlein, I Evangelakos, C Mineoet al. (2017) Cold-induced conversion of cholesterol to bile acids in mice shapes the gut microbiome and promotes adaptive thermogenesis. Nat Med 23:839–849
https://doi.org/10.1038/nm.4357
103 GD Wu, J Chen, C Hoffmann, K Bittinger, YY Chen, SA Keilbaugh, M Bewtra, D Knights, WA Walters, R Knightet al. (2011) Linking long-term dietary patterns with gut microbial enterotypes. Science 334:105–108
https://doi.org/10.1126/science.1208344
104 H Wu, E Esteve, V Tremaroli, MT Khan, R Caesar, L Manneras-Holm, M Stahlaman, LM Olsson, M Serino, M Planas-Felixet al. (2017) Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat Med 23:850–858
https://doi.org/10.1038/nm.4345
105 C Xie, C Jiang, J Shi, X Gao, D Sun, L Sun, T Wang, S Takahashi, M Anitha, KW Krauszet al. (2017) An intestinal farnesoid X receptor-ceramide signaling axis modulates hepatic gluconeogenesis in mice. Diabetes 66:613–626
https://doi.org/10.2337/db16-0663
106 CK Yao, JG Muir, PR Gibson (2016) Review article: insights into colonic protein fermentation, its modulation and potential health implications. Aliment Pharmacol Ther 43:181–196
https://doi.org/10.1111/apt.13456
107 ZM Younossi, AB Koenig, D Abdelatif, Y Fazel, L Henry, M Wymer (2016) Global epidemiology of nonalcoholic fatty liver diseasemeta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 64:73–84
https://doi.org/10.1002/hep.28431
108 D Zeevi, T Korem, N Zmora, D Israeli, D Rothschild, A Weinberger, O Ben-Yacov, D Lador, T Avnit-Sagi, M Lotan-Pompanet al. (2015) Personalized nutrition by prediction of glycemic responses. Cell 163:1079–1094
https://doi.org/10.1016/j.cell.2015.11.001
109 T Zelante, G Iannitti Rossana, C Cunha, A De Luca, G Giovannini, G Pieraccini, R Zecchi, C D’Angelo, C Massi-Benedetti, F Fallarinoet al. (2013) Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity 39:372–385
https://doi.org/10.1016/j.immuni.2013.08.003
110 Q Zhang, Y Li, L Chen (2015) Effect of berberine in treating type 2 diabetes mellitus and complications and its relevant mechanisms. China J Chin Mater Med 40:1660–1665
111 L Zhang, C Xie, RG Nichols, SH Chan, C Jiang, R Hao, PB Smith, J Cai, MN Simons, E Hatzakiset al. (2016) Farnesoid X receptor signaling shapes the gut microbiota and controls hepatic lipid metabolism. mSystems 1:e00070
https://doi.org/10.1128/mSystems.00070-16
112 W Zhang, JH Xu, T Yu, QK Chen (2019a) Effects of berberine and metformin on intestinal inflammation and gut microbiome composition in db/db mice. Biomed Pharmacother 118:109131
https://doi.org/10.1016/j.biopha.2019.109131
113 X Zhang, Y Zhang, P Wang, SY Zhang, Y Dong, G Zeng, Y Yan, L Sun, Q Wu, H Liuet al. (2019b) Adipocyte hypoxia-inducible factor 2alpha suppresses atherosclerosis by promoting adipose ceramide catabolism. Cell Metab 30(937–951):e935
https://doi.org/10.1016/j.cmet.2019.09.016
114 Z Zhang, H Zhou, X Zhou, J Sun, X Liang, Y Lv, L Bai, J Zhang, P Gong, T Liuet al. (2020) Lactobacillus casei YRL577 ameliorates markers of non-alcoholic fatty liver and alters expression of genes within the intestinal bile acid pathway. Br J Nutr.
https://doi.org/10.1017/S0007114520003001
115 Y Zheng, SH Ley, FB Hu (2018) Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol 14:88–98
https://doi.org/10.1038/nrendo.2017.151
116 L Zhu, SS Baker, C Gill, W Liu, R Alkhouri, RD Baker, SR Gill (2013) Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology 57:601–609
https://doi.org/10.1002/hep.26093
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