Crosstalk between gut microbiota and antidiabetic drug action
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  • 英文篇名:Crosstalk between gut microbiota and antidiabetic drug action
  • 作者:Yevheniia ; Kyriachenko ; Tetyana ; Falalyeyeva ; Oleksandr ; Korotkyi ; Nataliia ; Molochek ; Nazarii ; Kobyliak
  • 英文作者:Yevheniia Kyriachenko;Tetyana Falalyeyeva;Oleksandr Korotkyi;Nataliia Molochek;Nazarii Kobyliak;Educational and Scientific Centre "Institute of Biology and Medicine", Taras Shevchenko National University of Kyiv;Endocrinology Department, Bogomolets National Medical University;
  • 英文关键词:Type 2 diabetes;;Gut microbiota;;Metformin;;α-glucosidase inhibitors;;Glucagon-like peptide-1 agonists;;Peroxisome proliferator-activated receptors γ agonists;;Dipeptidyl peptidase-4 inhibitors;;Sodium/glucose cotransporter inhibitors
  • 中文刊名:WJDE
  • 英文刊名:世界糖尿病杂志(电子版)(英文版)
  • 机构:Educational and Scientific Centre "Institute of Biology and Medicine", Taras Shevchenko National University of Kyiv;Endocrinology Department, Bogomolets National Medical University;
  • 出版日期:2019-03-15
  • 出版单位:World Journal of Diabetes
  • 年:2019
  • 期:v.10
  • 语种:英文;
  • 页:WJDE201903003
  • 页数:15
  • CN:03
  • 分类号:22-36
摘要
Type 2 diabetes(T2 D) is a disorder characterized by chronic inflated blood glucose levels(hyperglycemia), at first due to insulin resistance and unregulated insulin secretion but with tendency towards global spreading. The gut microbiota is recognized to have an influence on T2 D, although surveys have not formed a clear overview to date. Because of the interactions between gut microbiota and host homeostasis, intestinal bacteria are believed to play a large role in various diseases, including metabolic syndrome, obesity and associated disease. In this review, we highlight the animal and human studies which have elucidated the roles of metformin, α-glucosidase inhibitors, glucagon-like peptide-1 agonists,peroxisome proliferator-activated receptors γ agonists, inhibitors of dipeptidyl peptidase-4, sodium/glucose cotransporter inhibitors, and other less studied medications on gut microbiota. This review is dedicated to one of the most widespread diseases, T2 D, and the currently used antidiabetic drugs and most promising new findings. In general, the gut microbiota has been shown to have an influence on host metabolism, food consumption, satiety, glucose homoeostasis, and weight gain. Altered intestinal microbiota composition has been noticed in cardiovascular diseases, colon cancer, rheumatoid arthritis, T2 D,and obesity. Therefore, the main effect of antidiabetic drugs is on the microbiome composition, basically increasing the short-chain fatty acids-producing bacteria,responsible for losing weight and suppressing inflammation.
        Type 2 diabetes(T2 D) is a disorder characterized by chronic inflated blood glucose levels(hyperglycemia), at first due to insulin resistance and unregulated insulin secretion but with tendency towards global spreading. The gut microbiota is recognized to have an influence on T2 D, although surveys have not formed a clear overview to date. Because of the interactions between gut microbiota and host homeostasis, intestinal bacteria are believed to play a large role in various diseases, including metabolic syndrome, obesity and associated disease. In this review, we highlight the animal and human studies which have elucidated the roles of metformin, α-glucosidase inhibitors, glucagon-like peptide-1 agonists,peroxisome proliferator-activated receptors γ agonists, inhibitors of dipeptidyl peptidase-4, sodium/glucose cotransporter inhibitors, and other less studied medications on gut microbiota. This review is dedicated to one of the most widespread diseases, T2 D, and the currently used antidiabetic drugs and most promising new findings. In general, the gut microbiota has been shown to have an influence on host metabolism, food consumption, satiety, glucose homoeostasis, and weight gain. Altered intestinal microbiota composition has been noticed in cardiovascular diseases, colon cancer, rheumatoid arthritis, T2 D,and obesity. Therefore, the main effect of antidiabetic drugs is on the microbiome composition, basically increasing the short-chain fatty acids-producing bacteria,responsible for losing weight and suppressing inflammation.
引文
1 Mykhalchyshyn G,Kobyliak N,Bodnar P.Diagnostic accuracy of acyl-ghrelin and it association with non-alcoholic fatty liver disease in type 2 diabetic patients.J Diabetes Metab Disord 2015;14:44[PMID:25995986 DOI:10.1186/s40200-015-0170-1]
    2 Qin J,Li Y,Cai Z,Li S,Zhu J,Zhang F,Liang S,Zhang W,Guan Y,Shen D,Peng Y,Zhang D,Jie Z,Wu W,Qin Y,Xue W,Li J,Han L,Lu D,Wu P,Dai Y,Sun X,Li Z,Tang A,Zhong S,Li X,Chen W,Xu R,Wang M,Feng Q,Gong M,Yu J,Zhang Y,Zhang M,Hansen T,Sanchez G,Raes J,Falony G,Okuda S,Almeida M,LeChatelier E,Renault P,Pons N,Batto JM,Zhang Z,Chen H,Yang R,Zheng W,Li S,Yang H,Wang J,Ehrlich SD,Nielsen R,Pedersen O,Kristiansen K,Wang J.A metagenome-wide association study of gut microbiota in type 2 diabetes.Nature 2012;490:55-60[PMID:23023125 DOI:10.1038/nature11450]
    3 Karlsson FH,Tremaroli V,Nookaew I,Bergstr?m G,Behre CJ,Fagerberg B,Nielsen J,B?ckhed F.Gut metagenome in European women with normal,impaired and diabetic glucose control.Nature 2013;498:99-103[PMID:23719380 DOI:10.1038/nature12198]
    4 Zhang X,Shen D,Fang Z,Jie Z,Qiu X,Zhang C,Chen Y,Ji L.Human gut microbiota changes reveal the progression of glucose intolerance.PLoS One 2013;8:e71108[PMID:24013136 DOI:10.1371/journal.pone.0071108]
    5 Montandon SA,Jornayvaz FR.Effects of Antidiabetic Drugs on Gut Microbiota Composition.Genes(Basel)2017;8:E250[PMID:28973971 DOI:10.3390/genes8100250]
    6 Napolitano A,Miller S,Nicholls AW,Baker D,Van Horn S,Thomas E,Rajpal D,Spivak A,Brown JR,Nunez DJ.Novel gut-based pharmacology of metformin in patients with type 2 diabetes mellitus.PLoSOne 2014;9:e100778[PMID:24988476 DOI:10.1371/journal.pone.0100778]
    7 Kobyliak N,Virchenko O,Falalyeyeva T.Pathophysiological role of host microbiota in the development of obesity.Nutr J 2016;15:43[PMID:27105827 DOI:10.1186/s12937-016-0166-9]
    8 Turnbaugh PJ,Hamady M,Yatsunenko T,Cantarel BL,Duncan A,Ley RE,Sogin ML,Jones WJ,Roe BA,Affourtit JP,Egholm M,Henrissat B,Heath AC,Knight R,Gordon JI.A core gut microbiome in obese and lean twins.Nature 2009;457:480-484[PMID:19043404 DOI:10.1038/nature07540]
    9 Woting A,Blaut M.The Intestinal Microbiota in Metabolic Disease.Nutrients 2016;8:202[PMID:27058556 DOI:10.3390/nu8040202]
    10 Murphy EF,Cotter PD,Healy S,Marques TM,O'Sullivan O,Fouhy F,Clarke SF,O'Toole PW,Quigley EM,Stanton C,Ross PR,O'Doherty RM,Shanahan F.Composition and energy harvesting capacity of the gut microbiota:relationship to diet,obesity and time in mouse models.Gut 2010;59:1635-1642[PMID:20926643 DOI:10.1136/gut.2010.215665]
    11 Brunkwall L,Orho-Melander M.The gut microbiome as a target for prevention and treatment of hyperglycaemia in type 2 diabetes:from current human evidence to future possibilities.Diabetologia2017;60:943-951[PMID:28434033 DOI:10.1007/s00125-017-4278-3]
    12 Forslund K,Hildebrand F,Nielsen T,Falony G,Le Chatelier E,Sunagawa S,Prifti E,Vieira-Silva S,Gudmundsdottir V,Pedersen HK,Arumugam M,Kristiansen K,Voigt AY,Vestergaard H,Hercog R,Costea PI,Kultima JR,Li J,J?rgensen T,Levenez F,Dore J;MetaHIT consortium,Nielsen HB,Brunak S,Raes J,Hansen T,Wang J,Ehrlich SD,Bork P,Pedersen O.Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota.Nature 2015;528:262-266[PMID:26633628 DOI:10.1038/nature15766]
    13 Wang L,Li P,Tang Z,Yan X,Feng B.Structural modulation of the gut microbiota and the relationship with body weight:compared evaluation of liraglutide and saxagliptin treatment.Sci Rep 2016;6:33251[PMID:27633081 DOI:10.1038/srep33251]
    14 Vrieze A,Holleman F,Zoetendal EG,de Vos WM,Hoekstra JB,Nieuwdorp M.The environment within:how gut microbiota may influence metabolism and body composition.Diabetologia 2010;53:606-613[PMID:20101384 DOI:10.1007/s00125-010-1662-7]
    15 Kobyliak N,Falalyeyeva T,Boyko N,Tsyryuk O,Beregova T,Ostapchenko L.Probiotics and nutraceuticals as a new frontier in obesity prevention and management.Diabetes Res Clin Pract 2018;141:190-199[PMID:29772287 DOI:10.1016/j.diabres.2018.05.005]
    16 Gu Y,Wang X,Li J,Zhang Y,Zhong H,Liu R,Zhang D,Feng Q,Xie X,Hong J,Ren H,Liu W,Ma J,Su Q,Zhang H,Yang J,Wang X,Zhao X,Gu W,Bi Y,Peng Y,Xu X,Xia H,Li F,Xu X,Yang H,Xu G,Madsen L,Kristiansen K,Ning G,Wang W.Analyses of gut microbiota and plasma bile acids enable stratification of patients for antidiabetic treatment.Nat Commun 2017;8:1785[PMID:29176714 DOI:10.1038/s41467-017-01682-2]
    17 Kobyliak N,Abenavoli L,Falalyeyeva T,Beregova T.Efficacy of Probiotics and Smectite in Rats with Non-Alcoholic Fatty Liver Disease.Ann Hepatol 2018;17:153-161[PMID:29311399 DOI:10.5604/01.3001.0010.7547]
    18 Kobyliak N,Falalyeyeva T,Bodnar P,Beregova T.Probiotics Supplemented with Omega-3 Fatty Acids are More Effective for Hepatic Steatosis Reduction in an Animal Model of Obesity.Probiotics Antimicrob Proteins 2017;9:123-130[PMID:27660157 DOI:10.1007/s12602-016-9230-1]
    19 Jourova L,Anzenbacher P,Anzenbacherova E.Human gut microbiota plays a role in the metabolism of drugs.Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2016;160:317-326[PMID:27485182DOI:10.5507/bp.2016.039]
    20 Yoo HH,Kim IS,Yoo DH,Kim DH.Effects of orally administered antibiotics on the bioavailability of amlodipine:gut microbiota-mediated drug interaction.J Hypertens 2016;34:156-162[PMID:26630218DOI:10.1097/HJH.0000000000000773]
    21 Kobyliak N,Falalyeyeva T,Virchenko O,Mykhalchyshyn G,Bodnar P,Spivak M,Yankovsky D,Beregova T,Ostapchenko L.Comparative experimental investigation on the efficacy of mono-and multiprobiotic strains in non-alcoholic fatty liver disease prevention.BMC Gastroenterol 2016;16:34[PMID:26976285 DOI:10.1186/s12876-016-0451-2]
    22 Kobyliak N,Falalyeyeva T,Beregova T,Spivak M.Probiotics for experimental obesity prevention:focus on strain dependence and viability of composition.Endokrynol Pol 2017;68:659-667[PMID:29022648DOI:10.5603/EP.a2017.0055]
    23 Kobyliak N,Falalyeyeva T,Mykhalchyshyn G,Kyriienko D,Komissarenko I.Effect of alive probiotic on insulin resistance in type 2 diabetes patients:Randomized clinical trial.Diabetes Metab Syndr 2018;12:617-624[PMID:29661605 DOI:10.1016/j.dsx.2018.04.015]
    24 Kobyliak N,Abenavoli L,Falalyeyeva T,Mykhalchyshyn G,Boccuto L,Kononenko L,Kyriienko D,Komisarenko I,Dynnyk O.Beneficial effects of probiotic combination with omega-3 fatty acids in NAFLD:a randomized clinical study.Minerva Med 2018;109:418-428[PMID:30221912 DOI:10.23736/S0026-4806.18.05845-7]
    25 Kobyliak N,Abenavoli L,Mykhalchyshyn G,Kononenko L,Boccuto L,Kyriienko D,Dynnyk O.AMulti-strain Probiotic Reduces the Fatty Liver Index,Cytokines and Aminotransferase levels in NAFLDPatients:Evidence from a Randomized Clinical Trial.J Gastrointestin Liver Dis 2018;27:41-49[PMID:29557414 DOI:10.15403/jgld.2014.1121.271.kby]
    26 Pernicova I,Korbonits M.Metformin--mode of action and clinical implications for diabetes and cancer.Nat Rev Endocrinol 2014;10:143-156[PMID:24393785 DOI:10.1038/nrendo.2013.256]
    27 Viollet B,Guigas B,Sanz Garcia N,Leclerc J,Foretz M,Andreelli F.Cellular and molecular mechanisms of metformin:an overview.Clin Sci(Lond)2012;122:253-270[PMID:22117616 DOI:10.1042/CS20110386]
    28 Hur KY,Lee MS.New mechanisms of metformin action:Focusing on mitochondria and the gut.JDiabetes Investig 2015;6:600-609[PMID:26543531 DOI:10.1111/jdi.12328]
    29 Devaraj S,Venkatachalam A,Chen X.Metformin and the Gut Microbiome in Diabetes.Clin Chem 2016;62:1554-1555[PMID:27650682 DOI:10.1373/clinchem.2016.256842]
    30 Kim J,Cheon H,Jeong YT,Quan W,Kim KH,Cho JM,Lim YM,Oh SH,Jin SM,Kim JH,Lee MK,Kim S,Komatsu M,Kang SW,Lee MS.Amyloidogenic peptide oligomer accumulation in autophagydeficientβcells induces diabetes.J Clin Invest 2014;124:3311-3324[PMID:25036705 DOI:10.1172/JCI69625]
    31 Lim YM,Lim H,Hur KY,Quan W,Lee HY,Cheon H,Ryu D,Koo SH,Kim HL,Kim J,Komatsu M,Lee MS.Systemic autophagy insufficiency compromises adaptation to metabolic stress and facilitates progression from obesity to diabetes.Nat Commun 2014;5:4934[PMID:25255859 DOI:10.1038/ncomms5934]
    32 Zhang X,Zhao Y,Xu J,Xue Z,Zhang M,Pang X,Zhang X,Zhao L.Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats.Sci Rep 2015;5:14405[PMID:26396057 DOI:10.1038/srep14405]
    33 Wu H,Esteve E,Tremaroli V,Khan MT,Caesar R,Manner?s-Holm L,St?hlman M,Olsson LM,Serino M,Planas-Fèlix M,Xifra G,Mercader JM,Torrents D,Burcelin R,Ricart W,Perkins R,Fernàndez-Real JM,B?ckhed F.Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes,contributing to the therapeutic effects of the drug.Nat Med 2017;23:850-858[PMID:28530702 DOI:10.1038/nm.4345]
    34 Lee H,Ko G.Effect of metformin on metabolic improvement and gut microbiota.Appl Environ Microbiol2014;80:5935-5943[PMID:25038099 DOI:10.1128/AEM.01357-14]
    35 Shin NR,Lee JC,Lee HY,Kim MS,Whon TW,Lee MS,Bae JW.An increase in the Akkermansia spp.population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice.Gut2014;63:727-735[PMID:23804561 DOI:10.1136/gutjnl-2012-303839]
    36 Everard A,Belzer C,Geurts L,Ouwerkerk JP,Druart C,Bindels LB,Guiot Y,Derrien M,Muccioli GG,Delzenne NM,de Vos WM,Cani PD.Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity.Proc Natl Acad Sci U S A 2013;110:9066-9071[PMID:23671105 DOI:10.1073/pnas.1219451110]
    37 Wu BN,O'Sullivan AJ.Sex differences in energy metabolism need to be considered with lifestyle modifications in humans.J Nutr Metab 2011;2011:391809[PMID:21773020 DOI:10.1155/2011/391809]
    38 Chiasson JL,Josse RG,Gomis R,Hanefeld M,Karasik A,Laakso M;STOP-NIDDM Trail Research Group.Acarbose for prevention of type 2 diabetes mellitus:the STOP-NIDDM randomised trial.Lancet2002;359:2072-2077[PMID:12086760 DOI:10.1016/S0140-6736(02)08905-5]
    39 Zhang X,Fang Z,Zhang C,Xia H,Jie Z,Han X,Chen Y,Ji L.Effects of Acarbose on the Gut Microbiota of Prediabetic Patients:A Randomized,Double-blind,Controlled Crossover Trial.Diabetes Ther 2017;8:293-307[PMID:28130771 DOI:10.1007/s13300-017-0226-y]
    40 Chiasson JL,Josse RG,Gomis R,Hanefeld M,Karasik A,Laakso M;STOP-NIDDM Trial Research Group.Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance:the STOP-NIDDM trial.JAMA 2003;290:486-494[PMID:12876091 DOI:10.1001/jama.290.4.486]
    41 Suzuki Y,Sano M,Hayashida K,Ohsawa I,Ohta S,Fukuda K.Are the effects of alpha-glucosidase inhibitors on cardiovascular events related to elevated levels of hydrogen gas in the gastrointestinal tract?FEBS Lett 2009;583:2157-2159[PMID:19505462 DOI:10.1016/j.febslet.2009.05.052]
    42 Panwar H,Calderwood D,Grant IR,Grover S,Green BD.Lactobacillus strains isolated from infant faeces possess potent inhibitory activity against intestinal alpha-and beta-glucosidases suggesting antidiabetic potential.Eur J Nutr 2014;53:1465-1474[PMID:24414142 DOI:10.1007/s00394-013-0649-9]
    43 Gao Z,Yin J,Zhang J,Ward RE,Martin RJ,Lefevre M,Cefalu WT,Ye J.Butyrate improves insulin sensitivity and increases energy expenditure in mice.Diabetes 2009;58:1509-1517[PMID:19366864DOI:10.2337/db08-1637]
    44 Koh A,De Vadder F,Kovatcheva-Datchary P,B?ckhed F.From Dietary Fiber to Host Physiology:ShortChain Fatty Acids as Key Bacterial Metabolites.Cell 2016;165:1332-1345[PMID:27259147 DOI:10.1016/j.cell.2016.05.041]
    45 Byron JS,Richard AM,Ericsson C,Harrison DC,Strong R,Schmidt TM.Changes in the gut microbiota and fermentation products associated with enhanced longevity in acarbose-treated mice.2018;bioRxiv:311456[DOI:10.1101/311456]
    46 Do HJ,Lee YS,Ha MJ,Cho Y,Yi H,Hwang YJ,Hwang GS,Shin MJ.Beneficial effects of voglibose administration on body weight and lipid metabolism via gastrointestinal bile acid modification.Endocr J2016;63:691-702[PMID:27349182 DOI:10.1507/endocrj.EJ15-0747]
    47 Liao Y,Takashima S,Zhao H,Asano Y,Shintani Y,Minamino T,Kim J,Fujita M,Hori M,Kitakaze M.Control of plasma glucose with alpha-glucosidase inhibitor attenuates oxidative stress and slows the progression of heart failure in mice.Cardiovasc Res 2006;70:107-116[PMID:16510136 DOI:10.1016/j.cardiores.2006.01.021]
    48 Do HJ,Jin T,Chung JH,Hwang JW,Shin MJ.Voglibose administration regulates body weight and energy intake in high fat-induced obese mice.Biochem Biophys Res Commun 2014;443:1110-1117[PMID:24388987 DOI:10.1016/j.bbrc.2013.12.120]
    49 Kishida Y,Okubo H,Ohno H,Oki K,Yoneda M.Effect of miglitol on the suppression of nonalcoholic steatohepatitis development and improvement of the gut environment in a rodent model.J Gastroenterol2017;52:1180-1191[PMID:28349245 DOI:10.1007/s00535-017-1331-4]
    50 Lieber CS,Leo MA,Mak KM,Xu Y,Cao Q,Ren C,Ponomarenko A,DeCarli LM.Acarbose attenuates experimental non-alcoholic steatohepatitis.Biochem Biophys Res Commun 2004;315:699-703[PMID:14975757 DOI:10.1016/j.bbrc.2004.01.116]
    51 Vieira EL,Leonel AJ,Sad AP,Beltr?o NR,Costa TF,Ferreira TM,Gomes-Santos AC,Faria AM,Peluzio MC,Cara DC,Alvarez-Leite JI.Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis.J Nutr Biochem 2012;23:430-436[PMID:21658926 DOI:10.1016/j.jnutbio.2011.01.007]
    52 Tan K,Tesar C,Wilton R,Jedrzejczak RP,Joachimiak A.Interaction of antidiabeticα-glucosidase inhibitors and gut bacteriaα-glucosidase.Protein Sci 2018;27:1498-1508[PMID:29761590 DOI:10.1002/pro.3444]
    53 Drucker DJ,Nauck MA.The incretin system:glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes.Lancet 2006;368:1696-1705[PMID:17098089 DOI:10.1016/S0140-6736(06)69705-5]
    54 Amato A,Cinci L,Rotondo A,Serio R,Faussone-Pellegrini MS,Vannucchi MG,MulèF.Peripheral motor action of glucagon-like peptide-1 through enteric neuronal receptors.Neurogastroenterol Motil2010;22:664-e203[PMID:20158614 DOI:10.1111/j.1365-2982.2010.01476.x]
    55 Aoki R,Kamikado K,Suda W,Takii H,Mikami Y,Suganuma N,Hattori M,Koga Y.A proliferative probiotic Bifidobacterium strain in the gut ameliorates progression of metabolic disorders via microbiota modulation and acetate elevation.Sci Rep 2017;7:43522[PMID:28252037 DOI:10.1038/srep43522]
    56 Vettorazzi JF,Ribeiro RA,Borck PC,Branco RC,Soriano S,Merino B,Boschero AC,Nadal A,Quesada I,Carneiro EM.The bile acid TUDCA increases glucose-induced insulin secretion via the cAMP/PKApathway in pancreatic beta cells.Metabolism 2016;65:54-63[PMID:26892516 DOI:10.1016/j.metabol.2015.10.021]
    57 Vilsb?ll T,Christensen M,Junker AE,Knop FK,Gluud LL.Effects of glucagon-like peptide-1 receptor agonists on weight loss:systematic review and meta-analyses of randomised controlled trials.BMJ 2012;344:d7771[PMID:22236411 DOI:10.1136/bmj.d7771]
    58 Tilg H,Moschen AR.Microbiota and diabetes:an evolving relationship.Gut 2014;63:1513-1521[PMID:24833634 DOI:10.1136/gutjnl-2014-306928]
    59 Zhao L,Chen Y,Xia F,Abudukerimu B,Zhang W,Guo Y,Wang N,Lu Y.A Glucagon-Like Peptide-1Receptor Agonist Lowers Weight by Modulating the Structure of Gut Microbiota.Front Endocrinol(Lausanne)2018;9:233[PMID:29867765 DOI:10.3389/fendo.2018.00233]
    60 Schwiertz A,Taras D,Sch?fer K,Beijer S,Bos NA,Donus C,Hardt PD.Microbiota and SCFA in lean and overweight healthy subjects.Obesity(Silver Spring)2010;18:190-195[PMID:19498350 DOI:10.1038/oby.2009.167]
    61 Wang Z,Saha S,Van Horn S.Gut microbiome differences between metformin and liraglutidetreated T2DM subjects.Endocrinol Diab Metab 2018;1:e9[PMID:30815546 DOI:10.1002/edm2.9]
    62 Pyke C,Heller RS,Kirk RK,?rskov C,Reedtz-Runge S,Kaastrup P,Hvelplund A,Bardram L,Calatayud D,Knudsen LB.GLP-1 receptor localization in monkey and human tissue:novel distribution revealed with extensively validated monoclonal antibody.Endocrinology 2014;155:1280-1290[PMID:24467746 DOI:10.1210/en.2013-1934]
    63 Heppner KM,Kirigiti M,Secher A,Paulsen SJ,Buckingham R,Pyke C,Knudsen LB,Vrang N,Grove KL.Expression and distribution of glucagon-like peptide-1 receptor mRNA,protein and binding in the male nonhuman primate(Macaca mulatta)brain.Endocrinology 2015;156:255-267[PMID:25380238DOI:10.1210/en.2014-1675]
    64 Nozu T,Miyagishi S,Kumei S,Nozu R,Takakusaki K,Okumura T.Glucagon-like peptide-1 analog,liraglutide,improves visceral sensation and gut permeability in rats.J Gastroenterol Hepatol 2018;33:232-239[PMID:28440889 DOI:10.1111/jgh.13808]
    65 Hellstr?m PM,Hein J,Bytzer P,Bj?rnss?n E,Kristensen J,Schambye H.Clinical trial:the glucagon-like peptide-1 analogue ROSE-010 for management of acute pain in patients with irritable bowel syndrome:a randomized,placebo-controlled,double-blind study.Aliment Pharmacol Ther 2009;29:198-206[PMID:18945254 DOI:10.1111/j.1365-2036.2008.03870.x]
    66 Voss U,Sand E,Olde B,Ekblad E.Enteric neuropathy can be induced by high fat diet in vivo and palmitic acid exposure in vitro.PLoS One 2013;8:e81413[PMID:24312551 DOI:10.1371/journal.pone.0081413]
    67 Grasset E,Puel A,Charpentier J,Collet X,Christensen JE,TercéF,Burcelin R.A Specific Gut Microbiota Dysbiosis of Type 2 Diabetic Mice Induces GLP-1 Resistance through an Enteric NO-Dependent and Gut-Brain Axis Mechanism.Cell Metab 2017;25:1075-1090.e5[PMID:28467926 DOI:10.1016/j.cmet.2017.04.013]
    68 Clemmensen C,Smajilovic S,Smith EP,Woods SC,Br?uner-Osborne H,Seeley RJ,D'Alessio DA,Ryan KK.Oral L-arginine stimulates GLP-1 secretion to improve glucose tolerance in male mice.Endocrinology 2013;154:3978-3983[PMID:23959939 DOI:10.1210/en.2013-1529]
    69 Seino Y,Fukushima M,Yabe D.GIP and GLP-1,the two incretin hormones:Similarities and differences.J Diabetes Investig 2010;1:8-23[PMID:24843404 DOI:10.1111/j.2040-1124.2010.00022.x]
    70 Olivares M,Schüppel V,Hassan AM,Beaumont M,Neyrinck AM,Bindels LB,Benítez-Páez A,Sanz Y,Haller D,Holzer P,Delzenne NM.The Potential Role of the Dipeptidyl Peptidase-4-Like Activity From the Gut Microbiota on the Host Health.Front Microbiol 2018;9:1900[PMID:30186247 DOI:10.3389/fmicb.2018.01900]
    71 Holzer P,Reichmann F,Farzi A.Neuropeptide Y,peptide YY and pancreatic polypeptide in the gut-brain axis.Neuropeptides 2012;46:261-274[PMID:22979996 DOI:10.1016/j.npep.2012.08.005]
    72 Zhong J,Gong Q,Goud A,Srinivasamaharaj S,Rajagopalan S.Recent Advances in DipeptidylPeptidase-4 Inhibition Therapy:Lessons from the Bench and Clinical Trials.J Diabetes Res 2015;2015:606031[PMID:26075284 DOI:10.1155/2015/606031]
    73 Ahmed RH,Huri HZ,Muniandy S,Al-Hamodi Z,Al-Absi B,Alsalahi A,Razif MF.Altered circulating concentrations of active glucagon-like peptide(GLP-1)and dipeptidyl peptidase 4(DPP4)in obese subjects and their association with insulin resistance.Clin Biochem 2017;50:746-749[PMID:28288852DOI:10.1016/j.clinbiochem.2017.03.008]
    74 Cani PD,Neyrinck AM,Maton N,Delzenne NM.Oligofructose promotes satiety in rats fed a high-fat diet:involvement of glucagon-like Peptide-1.Obes Res 2005;13:1000-1007[PMID:15976142 DOI:10.1038/oby.2005.117]
    75 Fteita D,Musrati AA,K?n?nen E,Ma X,Gürsoy M,Peurla M,S?derling E,Sintim HO,Gürsoy UK.Dipeptidyl peptidase IV and quorum sensing signaling in biofilm-related virulence of Prevotella aurantiaca.Anaerobe 2017;48:152-159[PMID:28821458 DOI:10.1016/j.anaerobe.2017.08.009]
    76 Stengel A,Goebel-Stengel M,Teuffel P,Hofmann T,Bu?e P,Kobelt P,Rose M,Klapp BF.Obese patients have higher circulating protein levels of dipeptidyl peptidase IV.Peptides 2014;61:75-82[PMID:25219943 DOI:10.1016/j.peptides.2014.09.006]
    77 Klemann C,Wagner L,Stephan M,von H?rsten S.Cut to the chase:a review of CD26/dipeptidyl peptidase-4's(DPP4)entanglement in the immune system.Clin Exp Immunol 2016;185:1-21[PMID:26919392 DOI:10.1111/cei.12781]
    78 Diouf I,Charles MA,Thiebaugeorges O,Forhan A,Kaminski M,Heude B;EDEN Mother-Child Cohort Study Group.Maternal weight change before pregnancy in relation to birthweight and risks of adverse pregnancy outcomes.Eur J Epidemiol 2011;26:789-796[PMID:21710259 DOI:10.1007/s10654-011-9599-9]
    79 Paul HA,Bomhof MR,Vogel HJ,Reimer RA.Diet-induced changes in maternal gut microbiota and metabolomic profiles influence programming of offspring obesity risk in rats.Sci Rep 2016;6:20683[PMID:26868870 DOI:10.1038/srep20683]
    80 Zhang Q,Xiao X,Li M,Yu M,Ping F,Zheng J,Wang T,Wang X.Vildagliptin increases butyrateproducing bacteria in the gut of diabetic rats.PLoS One 2017;12:e0184735[PMID:29036231 DOI:10.1371/journal.pone.0184735]
    81 Ryan PM,Patterson E,Carafa I,Mandal R.Metformin and a DPP-4 Inhibitor Differentially Modulate the Microbiome and Metabolome of Metabolic Syndrome Mice.Can J Diabetes 2018;42:S40[DOI:10.1016/j.jcjd.2018.08.120]
    82 Du F,Hinke SA,Cavanaugh C,Polidori D,Wallace N,Kirchner T,Jennis M,Lang W,Kuo GH,Gaul MD,Lenhard J,Demarest K,Ajami NJ,Liang Y,Hornby PJ.Potent Sodium/Glucose Cotransporter SGLT1/2 Dual Inhibition Improves Glycemic Control Without Marked Gastrointestinal Adaptation or Colonic Microbiota Changes in Rodents.J Pharmacol Exp Ther 2018;365:676-687[PMID:29674332DOI:10.1124/jpet.118.248575]
    83 Battson ML,Lee DM,Jarrell DK,Hou S,Ecton KE,Weir TL,Gentile CL.Suppression of gut dysbiosis reverses Western diet-induced vascular dysfunction.Am J Physiol Endocrinol Metab 2018;314:E468-E477[PMID:29351482 DOI:10.1152/ajpendo.00187.2017]
    84 Lee DM,Battson ML,Jarrell DK,Hou S,Ecton KE,Weir TL,Gentile CL.SGLT2 inhibition via dapagliflozin improves generalized vascular dysfunction and alters the gut microbiota in type 2 diabetic mice.Cardiovasc Diabetol 2018;17:62[PMID:29703207 DOI:10.1186/s12933-018-0708-x]
    85 Kuo GH,Gaul MD,Liang Y,Xu JZ,Du F,Hornby P,Xu G,Qi J,Wallace N,Lee S,Grant E,Murray WV,Demarest K.Synthesis and biological evaluation of benzocyclobutane-C-glycosides as potent and orally active SGLT1/SGLT2 dual inhibitors.Bioorg Med Chem Lett 2018;28:1182-1187[PMID:29523385 DOI:10.1016/j.bmcl.2018.02.057]
    86 Mudaliar S,Polidori D,Zambrowicz B,Henry RR.Sodium-Glucose Cotransporter Inhibitors:Effects on Renal and Intestinal Glucose Transport:From Bench to Bedside.Diabetes Care 2015;38:2344-2353[PMID:26604280 DOI:10.2337/dc15-0642]
    87 Zambrowicz B,Ding ZM,Ogbaa I,Frazier K,Banks P,Turnage A,Freiman J,Smith M,Ruff D,Sands A,Powell D.Effects of LX4211,a dual SGLT1/SGLT2 inhibitor,plus sitagliptin on postprandial active GLP-1 and glycemic control in type 2 diabetes.Clin Ther 2013;35:273-285.e7[PMID:23433601 DOI:10.1016/j.clinthera.2013.01.010]
    88 Lefterova MI,Lazar MA.New developments in adipogenesis.Trends Endocrinol Metab 2009;20:107-114[PMID:19269847 DOI:10.1016/j.tem.2008.11.005]
    89 Yoshizawa K,Cioca DP,Kawa S,Tanaka E,Kiyosawa K.Peroxisome proliferator-activated receptor gamma ligand troglitazone induces cell cycle arrest and apoptosis of hepatocellular carcinoma cell lines.Cancer 2002;95:2243-2251[PMID:12412180 DOI:10.1002/cncr.10906]
    90 Grimaldi PA.Peroxisome proliferator-activated receptors as sensors of fatty acids and derivatives.Cell Mol Life Sci 2007;64:2459-2464[PMID:17876521 DOI:10.1007/s00018-007-7278-5]
    91 Nepelska M,de Wouters T,Jacouton E,Béguet-Crespel F,Lapaque N,DoréJ,Arulampalam V,Blottière HM.Commensal gut bacteria modulate phosphorylation-dependent PPARγtranscriptional activity in human intestinal epithelial cells.Sci Rep 2017;7:43199[PMID:28266623 DOI:10.1038/srep43199]
    92 Brown PH,Lippman SM.Chemoprevention of breast cancer.Breast Cancer Res Treat 2000;62:1-17[PMID:10989982]
    93 Anghel SI,Wahli W.Fat poetry:a kingdom for PPAR gamma.Cell Res 2007;17:486-511[PMID:17563755 DOI:10.1038/cr.2007.48]
    94 Alex S,Lange K,Amolo T,Grinstead JS,Haakonsson AK,Szalowska E,Koppen A,Mudde K,Haenen D,Al-Lahham S,Roelofsen H,Houtman R,van der Burg B,Mandrup S,Bonvin AM,Kalkhoven E,Müller M,Hooiveld GJ,Kersten S.Short-chain fatty acids stimulate angiopoietin-like 4 synthesis in human colon adenocarcinoma cells by activating peroxisome proliferator-activated receptorγ.Mol Cell Biol 2013;33:1303-1316[PMID:23339868 DOI:10.1128/MCB.00858-12]
    95 Ortu?o Sahagún D,Márquez-Aguirre AL,Quintero-Fabián S,López-Roa RI,Rojas-Mayorquín AE.Modulation of PPAR-γby Nutraceutics as Complementary Treatment for Obesity-Related Disorders and Inflammatory Diseases.PPAR Res 2012;2012:318613[PMID:23251142 DOI:10.1155/2012/318613]
    96 Are A,Aronsson L,Wang S,Greicius G,Lee YK,Gustafsson JA,Pettersson S,Arulampalam V.Enterococcus faecalis from newborn babies regulate endogenous PPARgamma activity and IL-10 levels in colonic epithelial cells.Proc Natl Acad Sci U S A 2008;105:1943-1948[PMID:18234854 DOI:10.1073/pnas.0711734105]
    97 Scher JU,Sczesnak A,Longman RS,Segata N,Ubeda C,Bielski C,Rostron T,Cerundolo V,Pamer EG,Abramson SB,Huttenhower C,Littman DR.Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis.Elife 2013;2:e01202[PMID:24192039 DOI:10.7554/eLife.01202]
    98 Kumar PS,Griffen AL,Barton JA,Paster BJ,Moeschberger ML,Leys EJ.New bacterial species associated with chronic periodontitis.J Dent Res 2003;82:338-344[PMID:12709498]
    99 Rizos CV,Elisaf MS,Mikhailidis DP,Liberopoulos EN.How safe is the use of thiazolidinediones in clinical practice?Expert Opin Drug Saf 2009;8:15-32[PMID:19236215 DOI:10.1517/14740330802597821]
    100 Newman DJ,Cragg GM.Natural products as sources of new drugs over the 30 years from 1981 to 2010.JNat Prod 2012;75:311-335[PMID:22316239 DOI:10.1021/np200906s]
    101 Neschen S,Morino K,Dong J,Wang-Fischer Y,Cline GW,Romanelli AJ,Rossbacher JC,Moore IK,Regittnig W,Munoz DS,Kim JH,Shulman GI.n-3 Fatty acids preserve insulin sensitivity in vivo in a peroxisome proliferator-activated receptor-alpha-dependent manner.Diabetes 2007;56:1034-1041[PMID:17251275 DOI:10.2337/db06-1206]
    102 Puglisi MJ,Hasty AH,Saraswathi V.The role of adipose tissue in mediating the beneficial effects of dietary fish oil.J Nutr Biochem 2011;22:101-108[PMID:21145721 DOI:10.1016/j.jnutbio.2010.07.003]
    103 Kim MH,Kang SG,Park JH,Yanagisawa M,Kim CH.Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice.Gastroenterology 2013;145:396-406.e1-10[PMID:23665276 DOI:10.1053/j.gastro.2013.04.056]
    104 Puddu A,Sanguineti R,Montecucco F,Viviani GL.Evidence for the gut microbiota short-chain fatty acids as key pathophysiological molecules improving diabetes.Mediators Inflamm 2014;2014:162021[PMID:25214711 DOI:10.1155/2014/162021]
    105 Cani PD,Amar J,Iglesias MA,Poggi M,Knauf C,Bastelica D,Neyrinck AM,Fava F,Tuohy KM,Chabo C,Waget A,Delmée E,Cousin B,Sulpice T,Chamontin B,Ferrres J,Tanti JF,Gibson GR,Casteilla L,Delzenne NM,Alessi MC,Burcelin R.Metabolic endotoxemia initiates obesity and insulin resistance.Diabetes 2007;56:1761-1772[PMID:17456850 DOI:10.2337/db06-1491]
    106 Wu TR,Lin CS,Chang CJ,Lin TL,Martel J,Ko YF,Ojcius DM,Lu CC,Young JD,Lai HC.Gut commensal Parabacteroides goldsteinii plays a predominant role in the anti-obesity effects of polysaccharides isolated from Hirsutella sinensis.Gut 2019;68:248-262[PMID:30007918 DOI:10.1136/gutjnl-2017-315458]
    107 Cani PD,de Vos WM.Next-Generation Beneficial Microbes:The Case of Akkermansia muciniphila.Front Microbiol 2017;8:1765[PMID:29018410 DOI:10.3389/fmicb.2017.01765]
    108 Everard A,Lazarevic V,Derrien M,Girard M,Muccioli GG,Neyrinck AM,Possemiers S,Van Holle A,Fran?ois P,de Vos WM,Delzenne NM,Schrenzel J,Cani PD.Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice.Diabetes 2011;60:2775-2786[PMID:21933985 DOI:10.2337/db11-0227]
    109 Roopchand DE,Carmody RN,Kuhn P,Moskal K,Rojas-Silva P,Turnbaugh PJ,Raskin I.Dietary Polyphenols Promote Growth of the Gut Bacterium Akkermansia muciniphila and Attenuate High-Fat Diet-Induced Metabolic Syndrome.Diabetes 2015;64:2847-2858[PMID:25845659 DOI:10.2337/db14-1916]
    110 Zhang H,DiBaise JK,Zuccolo A,Kudrna D,Braidotti M,Yu Y,Parameswaran P,Crowell MD,Wing R,Rittmann BE,Krajmalnik-Brown R.Human gut microbiota in obesity and after gastric bypass.Proc Natl Acad Sci U S A 2009;106:2365-2370[PMID:19164560 DOI:10.1073/pnas.0812600106]
    111 Liou AP,Paziuk M,Luevano JM,Machineni S,Turnbaugh PJ,Kaplan LM.Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity.Sci Transl Med 2013;5:178ra41[PMID:23536013 DOI:10.1126/scitranslmed.3005687]
    112 Blandino G,Inturri R,Lazzara F,Di Rosa M,Malaguarnera L.Impact of gut microbiota on diabetes mellitus.Diabetes Metab 2016;42:303-315[PMID:27179626 DOI:10.1016/j.diabet.2016.04.004]
    113 Xu J,Lian F,Zhao L,Zhao Y,Chen X,Zhang X,Guo Y,Zhang C,Zhou Q,Xue Z,Pang X,Zhao L,Tong X.Structural modulation of gut microbiota during alleviation of type 2 diabetes with a Chinese herbal formula.ISME J 2015;9:552-562[PMID:25279787 DOI:10.1038/ismej.2014.177]