The Intestinal Microbiota in Metabolic Disease

Anni Woting, Michael Blaut, Anni Woting, Michael Blaut

Abstract

Gut bacteria exert beneficial and harmful effects in metabolic diseases as deduced from the comparison of germfree and conventional mice and from fecal transplantation studies. Compositional microbial changes in diseased subjects have been linked to adiposity, type 2 diabetes and dyslipidemia. Promotion of an increased expression of intestinal nutrient transporters or a modified lipid and bile acid metabolism by the intestinal microbiota could result in an increased nutrient absorption by the host. The degradation of dietary fiber and the subsequent fermentation of monosaccharides to short-chain fatty acids (SCFA) is one of the most controversially discussed mechanisms of how gut bacteria impact host physiology. Fibers reduce the energy density of the diet, and the resulting SCFA promote intestinal gluconeogenesis, incretin formation and subsequently satiety. However, SCFA also deliver energy to the host and support liponeogenesis. Thus far, there is little knowledge on bacterial species that promote or prevent metabolic disease. Clostridium ramosum and Enterococcus cloacae were demonstrated to promote obesity in gnotobiotic mouse models, whereas bifidobacteria and Akkermansia muciniphila were associated with favorable phenotypes in conventional mice, especially when oligofructose was fed. How diet modulates the gut microbiota towards a beneficial or harmful composition needs further research. Gnotobiotic animals are a valuable tool to elucidate mechanisms underlying diet-host-microbe interactions.

Keywords: SCFA; absorption; bile acids; diabetes; diet; energy harvest; intestinal microbiota; low-grade inflammation; metabolic syndrome; obesity.

Figures

Figure 1
Figure 1
Hypothetical interplay between diet, gut microbiota and host in prevention and promotion of metabolic diseases. Consequences of high-fat diets and fiber-rich diets are indicated in red and in blue, respectively.
Figure 2
Figure 2
Hypothetical scheme displaying possible contributions of intestinal microbiota to obesity development.

References

    1. Turnbaugh P.J., Hamady M., Yatsunenko T., Cantarel B.L., Duncan A., Ley R.E., Sogin M.L., Jones W.J., Roe B.A., Affourtit J.P., et al. A core gut microbiome in obese and lean twins. Nature. 2009;457:480–484. doi: 10.1038/nature07540.
    1. Hildebrandt M.A., Hoffmann C., Sherrill-Mix S.A., Keilbaugh S.A., Hamady M., Chen Y.Y., Knight R., Ahima R.S., Bushman F., Wu G.D. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology. 2009;137 doi: 10.1053/j.gastro.2009.08.042.
    1. Murphy E.F., Cotter P.D., Healy S., Marques T.M., O’Sullivan O., Fouhy F., Clarke S.F., O’Toole P.W., Quigley E.M., Stanton C., et al. Composition and energy harvesting capacity of the gut microbiota: Relationship to diet, obesity and time in mouse models. Gut. 2010;59:1635–1642. doi: 10.1136/gut.2010.215665.
    1. Maukonen J., Simoes C., Saarela M. The currently used commercial DNA-extraction methods give different results of clostridial and actinobacterial populations derived from human fecal samples. FEMS Microbiol. Ecol. 2012;79:697–708. doi: 10.1111/j.1574-6941.2011.01257.x.
    1. Eckburg P.B., Bik E.M., Bernstein C.N., Purdom E., Dethlefsen L., Sargent M., Gill S.R., Nelson K.E., Relman D.A. Diversity of the human intestinal microbial flora. Science. 2005;308:1635–1638. doi: 10.1126/science.1110591.
    1. Gill S.R., Pop M., Deboy R.T., Eckburg P.B., Turnbaugh P.J., Samuel B.S., Gordon J.I., Relman D.A., Fraser-Liggett C.M., Nelson K.E. Metagenomic analysis of the human distal gut microbiome. Science. 2006;312:1355–1359. doi: 10.1126/science.1124234.
    1. Flint H.J., Scott K.P., Duncan S.H., Louis P., Forano E. Microbial degradation of complex carbohydrates in the gut. Gut Microbes. 2012;3:289–306. doi: 10.4161/gmic.19897.
    1. D’Elia J.N., Salyers A.A. Effect of regulatory protein levels on utilization of starch by Bacteroides thetaiotaomicron. J. Bacteriol. 1996;178:7180–7186.
    1. Shipman J.A., Berleman J.E., Salyers A.A. Characterization of four outer membrane proteins involved in binding starch to the cell surface of Bacteroides thetaiotaomicron. J. Bacteriol. 2000;182:5365–5372. doi: 10.1128/JB.182.19.5365-5372.2000.
    1. Ze X., Ben David Y., Laverde-Gomez J.A., Dassa B., Sheridan P.O., Duncan S.H., Louis P., Henrissat B., Juge N., Koropatkin N.M., et al. Unique Organization of Extracellular Amylases into Amylosomes in the Resistant Starch-Utilizing Human Colonic Firmicutes Bacterium Ruminococcus bromii. mBio. 2015;6 doi: 10.1128/mBio.01058-15.
    1. Sonnenburg J.L., Xu J., Leip D.D., Chen C.H., Westover B.P., Weatherford J., Buhler J.D., Gordon J.I. Glycan foraging in vivo by an intestine-adapted bacterial symbiont. Science. 2005;307:1955–1959. doi: 10.1126/science.1109051.
    1. Turroni F., Bottacini F., Foroni E., Mulder I., Kim J.H., Zomer A., Sanchez B., Bidossi A., Ferrarini A., Giubellini V., et al. Genome analysis of Bifidobacterium bifidum PRL2010 reveals metabolic pathways for host-derived glycan foraging. Proc. Natl. Acad. Sci. USA. 2010;107:19514–19519. doi: 10.1073/pnas.1011100107.
    1. Derrien M., Collado M.C., Ben-Amor K., Salminen S., de Vos W.M. The mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract. Appl. Environ. Microbiol. 2008;74:1646–1648. doi: 10.1128/AEM.01226-07.
    1. Sonnenburg E.D., Sonnenburg J.L., Manchester J.K., Hansen E.E., Chiang H.C., Gordon J.I. A hybrid two-component system protein of a prominent human gut symbiont couples glycan sensing in vivo to carbohydrate metabolism. Proc. Natl. Acad. Sci. USA. 2006;103:8834–8839. doi: 10.1073/pnas.0603249103.
    1. Sonnenburg E.D., Zheng H., Joglekar P., Higginbottom S.K., Firbank S.J., Bolam D.N., Sonnenburg J.L. Specificity of polysaccharide use in intestinal bacteroides species determines diet-induced microbiota alterations. Cell. 2010;141:1241–1252. doi: 10.1016/j.cell.2010.05.005.
    1. Lynch J.B., Sonnenburg J.L. Prioritization of a plant polysaccharide over a mucus carbohydrate is enforced by a bacteroides hybrid two-component system. Mol. Microbiol. 2012;85:478–491. doi: 10.1111/j.1365-2958.2012.08123.x.
    1. Macfarlane G.T., Macfarlane S. Factors affecting fermentation reactions in the large bowel. Proc. Nutr. Soc. 1993;52:367–373. doi: 10.1079/PNS19930072.
    1. Smith E.A., Macfarlane G.T. Studies on amine production in the human colon: Enumeration of amine forming bacteria and physiological effects of carbohydrate and pH. Anaerobe. 1996;2:285–297. doi: 10.1006/anae.1996.0037.
    1. Smith E.A., Macfarlane G.T. Formation of phenolic and indolic compounds by anaerobic bacteria in the human large intestine. Microb. Ecol. 1997;33:180–188. doi: 10.1007/s002489900020.
    1. Smith E.A., Macfarlane G.T. Dissimilatory amino acid metabolism in human colonic bacteria. Anaerobe. 1997;3:327–337.
    1. Budnowski J., Hanske L., Schumacher F., Glatt H., Platz S., Rohn S., Blaut M. Glucosinolates are mainly absorbed intact in germfree and human microbiota-associated mice. J. Agric. Food. Chem. 2015;63:8418–8428. doi: 10.1021/acs.jafc.5b02948.
    1. Luang-In V., Narbad A., Nueno-Palop C., Mithen R., Bennett M., Rossiter J.T. The metabolism of methylsulfinylalkyl- and methylthioalkyl-glucosinolates by a selection of human gut bacteria. Mol. Nutr. Food Res. 2014;58:875–883. doi: 10.1002/mnfr.201300377.
    1. Braune A., Blaut M. Bacterial species involved in the conversion of dietary flavonoids in the human gut. Gut Microbes. 2016 doi: 10.1080/19490976.2016.1158395.
    1. Ridlon J.M., Kang D.J., Hylemon P.B., Bajaj J.S. Bile acids and the gut microbiome. Curr. Opin. Gastroenterol. 2014;30:332–338. doi: 10.1097/MOG.0000000000000057.
    1. Islam K.B.M.S., Fukiya S., Hagio M., Fujii N., Ishizuka S., Ooka T., Ogura Y., Hayashi T., Yokota A. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology. 2011;141:1773–1781. doi: 10.1053/j.gastro.2011.07.046.
    1. Backhed F., Ding H., Wang T., Hooper L.V., Koh G.Y., Nagy A., Semenkovich C.F., Gordon J.I. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. USA. 2004;101:15718–15723. doi: 10.1073/pnas.0407076101.
    1. Backhed F., Manchester J.K., Semenkovich C.F., Gordon J.I. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc. Natl. Acad. Sci. USA. 2007;104:979–984. doi: 10.1073/pnas.0605374104.
    1. Samuel B.S., Shaito A., Motoike T., Rey F.E., Backhed F., Manchester J.K., Hammer R.E., Williams S.C., Crowley J., Yanagisawa M., et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, GPR41. Proc. Natl. Acad. Sci. USA. 2008;105:16767–16772. doi: 10.1073/pnas.0808567105.
    1. Rabot S., Membrez M., Bruneau A., Gerard P., Harach T., Moser M., Raymond F., Mansourian R., Chou C.J. Germ-free C57BL/6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolism. FASEB J. 2010;24:4948–4959. doi: 10.1096/fj.10-164921.
    1. Fleissner C.K., Huebel N., Abd El-Bary M.M., Loh G., Klaus S., Blaut M. Absence of intestinal microbiota does not protect mice from diet-induced obesity. Br. J. Nutr. 2010;104:919–929. doi: 10.1017/S0007114510001303.
    1. Turnbaugh P.J., Ley R.E., Mahowald M.A., Magrini V., Mardis E.R., Gordon J.I. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027–1031. doi: 10.1038/nature05414.
    1. Turnbaugh P.J., Ridaura V.K., Faith J.J., Rey F.E., Knight R., Gordon J.I. The effect of diet on the human gut microbiome: A metagenomic analysis in humanized gnotobiotic mice. Sci. Transl. Med. 2009;1:6ra14. doi: 10.1126/scitranslmed.3000322.
    1. Ridaura V.K., Faith J.J., Rey F.E., Cheng J., Duncan A.E., Kau A.L., Griffin N.W., Lombard V., Henrissat B., Bain J.R., et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341:1241214. doi: 10.1126/science.1241214.
    1. Faith J.J., McNulty N.P., Rey F.E., Gordon J.I. Predicting a human gut microbiota’s response to diet in gnotobiotic mice. Science. 2011;333:101–104. doi: 10.1126/science.1206025.
    1. David L.A., Maurice C.F., Carmody R.N., Gootenberg D.B., Button J.E., Wolfe B.E., Ling A.V., Devlin A.S., Varma Y., Fischbach M.A., et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559–563. doi: 10.1038/nature12820.
    1. Carmody R.N., Gerber G.K., Luevano J.M., Jr., Gatti D.M., Somes L., Svenson K.L., Turnbaugh P.J. Diet dominates host genotype in shaping the murine gut microbiota. Cell Host Microbe. 2015;17:72–84. doi: 10.1016/j.chom.2014.11.010.
    1. Turnbaugh P.J., Backhed F., Fulton L., Gordon J.I. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe. 2008;3:213–223. doi: 10.1016/j.chom.2008.02.015.
    1. Ley R.E., Backhed F., Turnbaugh P., Lozupone C.A., Knight R.D., Gordon J.I. Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. USA. 2005;102:11070–11075. doi: 10.1073/pnas.0504978102.
    1. Ley R.E., Turnbaugh P.J., Klein S., Gordon J.I. Microbial ecology: Human gut microbes associated with obesity. Nature. 2006;444:1022–1023. doi: 10.1038/4441022a.
    1. Furet J.P., Kong L.C., Tap J., Poitou C., Basdevant A., Bouillot J.L., Mariat D., Corthier G., Dore J., Henegar C., et al. Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: Links with metabolic and low-grade inflammation markers. Diabetes. 2010;59:3049–3057. doi: 10.2337/db10-0253.
    1. Louis S., Tappu R.M., Damms-Machado A., Huson D.H., Bischoff S.C. Characterization of the gut microbial community of obese patients following a weight-loss intervention using whole metagenome shotgun sequencing. PLoS ONE. 2016;11:202. doi: 10.1371/journal.pone.0149564.
    1. Duncan S.H., Lobley G.E., Holtrop G., Ince J., Johnstone A.M., Louis P., Flint H.J. Human colonic microbiota associated with diet, obesity and weight loss. Int. J. Obes. 2008;32:1720–1724. doi: 10.1038/ijo.2008.155.
    1. Schwiertz A., Taras D., Schafer K., Beijer S., Bos N.A., Donus C., Hardt P.D. Microbiota and scfa in lean and overweight healthy subjects. Obesity. 2010;18:190–195. doi: 10.1038/oby.2009.167.
    1. Devkota S., Wang Y., Musch M.W., Leone V., Fehlner-Peach H., Nadimpalli A., Antonopoulos D.A., Jabri B., Chang E.B. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in il10-/- mice. Nature. 2012;487:104–108. doi: 10.1038/nature11225.
    1. Samuel B.S., Gordon J.I. A humanized gnotobiotic mouse model of host-archaeal-bacterial mutualism. Proc. Natl. Acad. Sci. USA. 2006;103:10011–10016. doi: 10.1073/pnas.0602187103.
    1. Isken F., Klaus S., Osterhoff M., Pfeiffer A.F., Weickert M.O. Effects of long-term soluble vs. Insoluble dietary fiber intake on high-fat diet-induced obesity in C57BL/6J mice. J. Nutr. Biochem. 2010;21:278–284. doi: 10.1016/j.jnutbio.2008.12.012.
    1. InterAct C. Dietary fibre and incidence of type 2 diabetes in eight european countries: The epic-interact study and a meta-analysis of prospective studies. Diabetologia. 2015;58:1394–1408.
    1. Slavin J.L. Dietary fiber and body weight. Nutrition. 2005;21:411–418. doi: 10.1016/j.nut.2004.08.018.
    1. De Munter J.S., Hu F.B., Spiegelman D., Franz M., van Dam R.M. Whole grain, bran, and germ intake and risk of type 2 diabetes: A prospective cohort study and systematic review. PLoS Med. 2007;4:202. doi: 10.1371/journal.pmed.0040261.
    1. Rahat-Rozenbloom S., Fernandes J., Gloor G.B., Wolever T.M.S. Evidence for greater production of colonic short-chain fatty acids in overweight than lean humans. Int. J. Obes. 2014;38:1525–1531. doi: 10.1038/ijo.2014.46.
    1. Teixeira T.F., Grzeskowiak L., Franceschini S.C., Bressan J., Ferreira C.L., Peluzio M.C. Higher level of faecal scfa in women correlates with metabolic syndrome risk factors. Br. J. Nutr. 2013;109:914–919. doi: 10.1017/S0007114512002723.
    1. Weickert M.O., Arafat A.M., Blaut M., Alpert C., Becker N., Leupelt V., Rudovich N., Mohlig M., Pfeiffer A.F. Changes in dominant groups of the gut microbiota do not explain cereal-fiber induced improvement of whole-body insulin sensitivity. Nutr. Metab. 2011;8:90. doi: 10.1186/1743-7075-8-90.
    1. Weickert M.O., Roden M., Isken F., Hoffmann D., Nowotny P., Osterhoff M., Blaut M., Alpert C., Gogebakan O., Bumke-Vogt C., et al. Effects of supplemented isoenergetic diets differing in cereal fiber and protein content on insulin sensitivity in overweight humans. Am. J. Clin. Nutr. 2011;94:459–471. doi: 10.3945/ajcn.110.004374.
    1. Hooper L.V., Wong M.H., Thelin A., Hansson L., Falk P.G., Gordon J.I. Molecular analysis of commensal host-microbial relationships in the intestine. Science. 2001;291:881–884. doi: 10.1126/science.291.5505.881.
    1. Woting A., Pfeiffer N., Loh G., Klaus S., Blaut M. Clostridium ramosum promotes high-fat diet-induced obesity in gnotobiotic mouse models. mBio. 2014;5 doi: 10.1128/mBio.01530-14.
    1. Wostmann B.S. The germfree animal in nutritional studies. Annu. Rev. Nutr. 1981;1:257–279. doi: 10.1146/annurev.nu.01.070181.001353.
    1. Sayin S.I., Wahlstrom A., Felin J., Jantti S., Marschall H.U., Bamberg K., Angelin B., Hyotylainen T., Oresic M., Backhed F. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring fxr antagonist. Cell Metab. 2013;17:225–235. doi: 10.1016/j.cmet.2013.01.003.
    1. Begley M., Hill C., Gahan C.G. Bile salt hydrolase activity in probiotics. Appl. Environ. Microbiol. 2006;72:1729–1738. doi: 10.1128/AEM.72.3.1729-1738.2006.
    1. Semova I., Carten J.D., Stombaugh J., Mackey L.C., Knight R., Farber S.A., Rawls J.F. Microbiota regulate intestinal absorption and metabolism of fatty acids in the zebrafish. Cell Host Microbe. 2012;12:277–288. doi: 10.1016/j.chom.2012.08.003.
    1. Duca F.A., Swartz T.D., Sakar Y., Covasa M. Increased oral detection, but decreased intestinal signaling for fats in mice lacking gut microbiota. PLoS ONE. 2012;7:202. doi: 10.1371/journal.pone.0039748.
    1. Wang T.Y., Liu M., Portincasa P., Wang D.Q.H. New insights into the molecular mechanism of intestinal fatty acid absorption. Eur. J. Clin. Investig. 2013;43:1203–1223. doi: 10.1111/eci.12161.
    1. Voshol P.J., Rensen P.C., van Dijk K.W., Romijn J.A., Havekes L.M. Effect of plasma triglyceride metabolism on lipid storage in adipose tissue: Studies using genetically engineered mouse models. Biochim. Biophys. Acta. 2009;1791:479–485. doi: 10.1016/j.bbalip.2008.12.015.
    1. Kim I., Kim H.G., Kim H., Kim H.H., Park S.K., Uhm C.S., Lee Z.H., Koh G.Y. Hepatic expression, synthesis and secretion of a novel fibrinogen/angiopoietin-related protein that prevents endothelial-cell apoptosis. Biochem. J. 2000;346 Pt 3:603–610. doi: 10.1042/bj3460603.
    1. Kersten S., Mandard S., Tan N.S., Escher P., Metzger D., Chambon P., Gonzalez F.J., Desvergne B., Wahli W. Characterization of the fasting-induced adipose factor fiaf, a novel peroxisome proliferator-activated receptor target gene. J. Biol. Chem. 2000;275:28488–28493. doi: 10.1074/jbc.M004029200.
    1. Yoon J.C., Chickering T.W., Rosen E.D., Dussault B., Qin Y., Soukas A., Friedman J.M., Holmes W.E., Spiegelman B.M. Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation. Mol. Cell Biol. 2000;20:5343–5349. doi: 10.1128/MCB.20.14.5343-5349.2000.
    1. Sukonina V., Lookene A., Olivecrona T., Olivecrona G. Angiopoietin-like protein 4 converts lipoprotein lipase to inactive monomers and modulates lipase activity in adipose tissue. Proc. Natl. Acad. Sci. USA. 2006;103:17450–17455. doi: 10.1073/pnas.0604026103.
    1. Lichtenstein L., Kersten S. Modulation of plasma TG lipolysis by angiopoietin-like proteins and GPIHBP1. Biochim. Biophys. Acta. 2010;1801:415–420. doi: 10.1016/j.bbalip.2009.12.015.
    1. Mandard S., Zandbergen F., van Straten E., Wahli W., Kuipers F., Muller M., Kersten S. The fasting-induced adipose factor/angiopoietin-like protein 4 is physically associated with lipoproteins and governs plasma lipid levels and adiposity. J. Biol. Chem. 2006;281:934–944. doi: 10.1074/jbc.M506519200.
    1. Aronsson L., Huang Y., Parini P., Korach-Andre M., Hakansson J., Gustafsson J.A., Pettersson S., Arulampalam V., Rafter J. Decreased fat storage by lactobacillus paracasei is associated with increased levels of angiopoietin-like 4 protein (ANGPTL4) PLoS ONE. 2010;5 doi: 10.1371/journal.pone.0013087.
    1. Blaut M., Klaus S. Intestinal microbiota and obesity. Handb. Exp. Pharmacol. 2012:251–273. doi: 10.1007/978-3-642-24716-3_11.
    1. Brown A.J., Goldsworthy S.M., Barnes A.A., Eilert M.M., Tcheang L., Daniels D., Muir A.I., Wigglesworth M.J., Kinghorn I., Fraser N.J., et al. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J. Biol. Chem. 2003;278:11312–11319. doi: 10.1074/jbc.M211609200.
    1. Xiong Y., Miyamoto N., Shibata K., Valasek M.A., Motoike T., Kedzierski R.M., Yanagisawa M. Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41. Proc. Natl. Acad. Sci. USA. 2004;101:1045–1050. doi: 10.1073/pnas.2637002100.
    1. Tazoe H., Otomo Y., Kaji I., Tanaka R., Karaki S.I., Kuwahara A. Roles of short-chain fatty acids receptors, GPR41 and GPR43 on colonic functions. J. Physiol. Pharmacol. 2008;59(Suppl. 2):251–262.
    1. Spreckley E., Murphy K.G. The L-cell in nutritional sensing and the regulation of appetite. Front. Nutr. 2015;2:23. doi: 10.3389/fnut.2015.00023.
    1. Tolhurst G., Heffron H., Lam Y.S., Parker H.E., Habib A.M., Diakogiannaki E., Cameron J., Grosse J., Reimann F., Gribble F.M. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2012;61:364–371. doi: 10.2337/db11-1019.
    1. Chambers E.S., Viardot A., Psichas A., Morrison D.J., Murphy K.G., Zac-Varghese S.E., MacDougall K., Preston T., Tedford C., Finlayson G.S., et al. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut. 2015;64:1744–1754. doi: 10.1136/gutjnl-2014-307913.
    1. Blaut M. Gut microbiota and energy balance: Role in obesity. Proc. Nutr. Soc. 2015;74:227–234. doi: 10.1017/S0029665114001700.
    1. De Vadder F., Kovatcheva-Datchary P., Goncalves D., Vinera J., Zitoun C., Duchampt A., Backhed F., Mithieux G. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell. 2014;156:84–96. doi: 10.1016/j.cell.2013.12.016.
    1. Delaere F., Duchampt A., Mounien L., Seyer P., Duraffourd C., Zitoun C., Thorens B., Mithieux G. The role of sodium-coupled glucose co-transporter 3 in the satiety effect of portal glucose sensing. Mol. Metab. 2012;2:47–53. doi: 10.1016/j.molmet.2012.11.003.
    1. Mithieux G. Nutrient control of energy homeostasis via gut-brain neural circuits. Neuroendocrinology. 2014;100:89–94. doi: 10.1159/000369070.
    1. Wang A., Si H., Liu D., Jiang H. Butyrate activates the cAMP-protein kinase A-cAMP response element-binding protein signaling pathway in Caco-2 cells. J. Nutr. 2012;142:1–6. doi: 10.3945/jn.111.148155.
    1. Hotamisligil G.S. Inflammation and metabolic disorders. Nature. 2006;444:860–867. doi: 10.1038/nature05485.
    1. Cani P.D., Osto M., Geurts L., Everard A. Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut Microbes. 2012;3:279–288. doi: 10.4161/gmic.19625.
    1. Creely S.J., McTernan P.G., Kusminski C.M., Fisher F.M., Da Silva N.F., Khanolkar M., Evans M., Harte A.L., Kumar S. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am. J. Physiol. Endocrinol. Metab. 2007;292:E740–E747. doi: 10.1152/ajpendo.00302.2006.
    1. Cani P.D., Amar J., Iglesias M.A., Poggi M., Knauf C., Bastelica D., Neyrinck A.M., Fava F., Tuohy K.M., Chabo C., et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56:1761–1772. doi: 10.2337/db06-1491.
    1. Erridge C., Attina T., Spickett C.M., Webb D.J. A high-fat meal induces low-grade endotoxemia: Evidence of a novel mechanism of postprandial inflammation. Am. J. Clin. Nutr. 2007;86:1286–1292.
    1. Amar J., Burcelin R., Ruidavets J.B., Cani P.D., Fauvel J., Alessi M.C., Chamontin B., Ferrieres J. Energy intake is associated with endotoxemia in apparently healthy men. Am. J. Clin. Nutr. 2008;87:1219–1223.
    1. Kitchens R.L., Thompson P.A. Modulatory effects of sCD14 and LBP on LPS-host cell interactions. J. Endotoxin Res. 2005;11:225–229. doi: 10.1177/09680519050110040701.
    1. Hersoug L.G., Moller P., Loft S. Gut microbiota-derived lipopolysaccharide uptake and trafficking to adipose tissue: Implications for inflammation and obesity. Obes. Rev. 2016;17:297–312. doi: 10.1111/obr.12370.
    1. Kim K.A., Gu W., Lee I.A., Joh E.H., Kim D.H. High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PLoS ONE. 2012;7:202. doi: 10.1371/journal.pone.0047713.
    1. Liu J., Batkai S., Pacher P., Harvey-White J., Wagner J.A., Cravatt B.F., Gao B., Kunos G. Lipopolysaccharide induces anandamide synthesis in macrophages via CD14/MAPK/phosphoinositide 3-kinase/NF-kappaB independently of platelet-activating factor. J. Biol. Chem. 2003;278:45034–45039. doi: 10.1074/jbc.M306062200.
    1. Muccioli G.G., Naslain D., Backhed F., Reigstad C.S., Lambert D.M., Delzenne N.M., Cani P.D. The endocannabinoid system links gut microbiota to adipogenesis. Mol. Syst. Biol. 2010;6:392. doi: 10.1038/msb.2010.46.
    1. Kless C., Muller V.M., Schuppel V.L., Lichtenegger M., Rychlik M., Daniel H., Klingenspor M., Haller D. Diet-induced obesity causes metabolic impairment independent of alterations in gut barrier integrity. Mol. Nutr. Food Res. 2015;59:968–978. doi: 10.1002/mnfr.201400840.
    1. Johnson R.J., Rivard C., Lanaspa M.A., Otabachian-Smith S., Ishimoto T., Cicerchi C., Cheeke P.R., Macintosh B., Hess T. Fructokinase, fructans, intestinal permeability, and metabolic syndrome: An equine connection? J. Equine Vet. Sci. 2013;33:120–126. doi: 10.1016/j.jevs.2012.05.004.
    1. Ferrer M., Ruiz A., Lanza F., Haange S.B., Oberbach A., Till H., Bargiela R., Campoy C., Segura M.T., Richter M., et al. Microbiota from the distal guts of lean and obese adolescents exhibit partial functional redundancy besides clear differences in community structure. Environ. Microbiol. 2013;15:211–226. doi: 10.1111/j.1462-2920.2012.02845.x.
    1. Karlsson F.H., Tremaroli V., Nookaew I., Bergstrom G., Behre C.J., Fagerberg B., Nielsen J., Backhed F. Gut metagenome in european women with normal, impaired and diabetic glucose control. Nature. 2013;498:99–103. doi: 10.1038/nature12198.
    1. Le Chatelier E., Nielsen T., Qin J., Prifti E., Hildebrand F., Falony G., Almeida M., Arumugam M., Batto J.M., Kennedy S., et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500:541–546. doi: 10.1038/nature12506.
    1. Fei N., Zhao L. An opportunistic pathogen isolated from the gut of an obese human causes obesity in germfree mice. ISME J. 2013;7:880–884. doi: 10.1038/ismej.2012.153.
    1. Faith J.J., Ahern P.P., Ridaura V.K., Cheng J., Gordon J.I. Identifying gut microbe-host phenotype relationships using combinatorial communities in gnotobiotic mice. Sci. Transl. Med. 2014;6:220ra211. doi: 10.1126/scitranslmed.3008051.
    1. Everard A., Belzer C., Geurts L., Ouwerkerk J.P., Druart C., Bindels L.B., Guiot Y., Derrien M., Muccioli G.G., Delzenne N.M., et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl. Acad. Sci. USA. 2013;110:9066–9071. doi: 10.1073/pnas.1219451110.
    1. Roopchand D.E., Carmody R.N., Kuhn P., Moskal K., Rojas-Silva P., Turnbaugh P.J., 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. doi: 10.2337/db14-1916.
    1. Dao M.C., Everard A., Aron-Wisnewsky J., Sokolovska N., Prifti E., Verger E.O., Kayser B.D., Levenez F., Chilloux J., Hoyles L., et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: Relationship with gut microbiome richness and ecology. Gut. 2016;65:426–436. doi: 10.1136/gutjnl-2014-308778.
    1. Shin N.R., Lee J.C., Lee H.Y., Kim M.S., Whon T.W., Lee M.S., Bae J.W. An increase in the Akkermansia spp. Population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut. 2014;63:727–735. doi: 10.1136/gutjnl-2012-303839.
    1. Behnsen J., Deriu E., Sassone-Corsi M., Raffatellu M. Probiotics: Properties, examples, and specific applications. Cold Spring Harb. Perspect. Med. 2013;3:a010074. doi: 10.1101/cshperspect.a010074.
    1. Million M., Angelakis E., Paul M., Armougom F., Leibovici L., Raoult D. Comparative meta-analysis of the effect of lactobacillus species on weight gain in humans and animals. Microb. Pathog. 2012;53:100–108. doi: 10.1016/j.micpath.2012.05.007.
    1. Park D.Y., Ahn Y.T., Park S.H., Huh C.S., Yoo S.R., Yu R., Sung M.K., McGregor R.A., Choi M.S. Supplementation of Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 in diet-induced obese mice is associated with gut microbial changes and reduction in obesity. PLoS ONE. 2013;8:202
    1. Wu C.C., Weng W.L., Lai W.L., Tsai H.P., Liu W.H., Lee M.H., Tsai Y.C. Effect of Lactobacillus plantarum strain K21 on high-fat diet-fed obese mice. Evid. Based Complement. Altern. Med. 2015;2015:391767. doi: 10.1155/2015/391767.
    1. Kadooka Y., Sato M., Ogawa A., Miyoshi M., Uenishi H., Ogawa H., Ikuyama K., Kagoshima M., Tsuchida T. Effect of Lactobacillus gasseri SBT2055 in fermented milk on abdominal adiposity in adults in a randomised controlled trial. Br. J. Nutr. 2013;110:1696–1703. doi: 10.1017/S0007114513001037.
    1. Collado M.C., Isolauri E., Laitinen K., Salminen S. Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am. J. Clin. Nutr. 2008;88:894–899.
    1. Kalliomaki M., Collado M.C., Salminen S., Isolauri E. Early differences in fecal microbiota composition in children may predict overweight. Am. J. Clin. Nutr. 2008;87:534–538.
    1. Wu X., Ma C., Han L., Nawaz M., Gao F., Zhang X., Yu P., Zhao C., Li L., Zhou A., et al. Molecular characterisation of the faecal microbiota in patients with type II diabetes. Curr. Microbiol. 2010;61:69–78. doi: 10.1007/s00284-010-9582-9.
    1. Cani P.D., Neyrinck A.M., Fava F., Knauf C., Burcelin R.G., Tuohy K.M., Gibson G.R., Delzenne N.M. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007;50:2374–2383. doi: 10.1007/s00125-007-0791-0.
    1. Cani P.D., Knauf C., Iglesias M.A., Drucker D.J., Delzenne N.M., Burcelin R. Improvement of glucose tolerance and hepatic insulin sensitivity by oligofructose requires a functional glucagon-like peptide 1 receptor. Diabetes. 2006;55:1484–1490. doi: 10.2337/db05-1360.
    1. Woting A., Pfeiffer N., Hanske L., Loh G., Klaus S., Blaut M. Alleviation of high fat diet-induced obesity by oligofructose in gnotobiotic mice is independent of presence of bifidobacterium longum. Mol. Nutr. Food Res. 2015;59:2267–2278. doi: 10.1002/mnfr.201500249.
    1. Kondo S., Xiao J.Z., Satoh T., Odamaki T., Takahashi S., Sugahara H., Yaeshima T., Iwatsuki K., Kamei A., Abe K. Antiobesity effects of Bifidobacterium breve strain B-3 supplementation in a mouse model with high-fat diet-induced obesity. Biosci. Biotechnol. Biochem. 2010;74:1656–1661. doi: 10.1271/bbb.100267.
    1. Stenman L.K., Waget A., Garret C., Klopp P., Burcelin R., Lahtinen S. Potential probiotic Bifidobacterium animalis ssp. lactis 420 prevents weight gain and glucose intolerance in diet-induced obese mice. Benef. Microbes. 2014;5:437–445. doi: 10.3920/BM2014.0014.
    1. Minami J., Kondo S., Yanagisawa N., Odamaki T., Xiao J.Z., Abe F., Nakajima S., Hamamoto Y., Saitoh S., Shimoda T. Oral administration of Bifidobacterium breve B-3 modifies metabolic functions in adults with obese tendencies in a randomised controlled trial. J. Nutr. Sci. 2015;4:e17. doi: 10.1017/jns.2015.5.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir