The role of gut microbiota in the pathogenesis of obesity
Agnieszka Żak-Gołąb 1 , Magdalena Olszanecka-Glinianowicz 2 , Piotr Kocełak 2 , Jerzy Chudek 1Abstract
Obesity is a disease that develops as a result of long-term positive energy balance. In recent years, the influence of gut microflora composition, as a potential factor affecting the energy balance and contributing to fat accumulation, has been studied. It seems that bacteria can affect host energy balance through several mechanisms, such as increased fermentation of undigested polysaccharides and obtaining extra energy from the portion of food, reduced expression of FIAF (fasting-induced adipocyte factor) in the enterocytes with inhibitory activity towards intestinal lipoprotein lipase, and the increased release of peptide YY that slows the intestinal motility.It is also believed that changes in the composition of gut microflora may be one of the factors that induce systemic microinflammation in the obese, an important link in the pathogenesis of obesity related complications, including dyslipidaemia, hypertension and type 2 diabetes. However, the results of previous studies are inconclusive. Many of them have been carried out in an animal model and were not confirmed in studies involving humans. These discrepancies may be due to different composition of the diet, distinct physiological gut microflora and the methodology used in these studies.The present article reviews the current literature on the potential role of gut microflora in the pathogenesis of obesity.
References
- 1. Amar J., Burcelin R., Ruidavets J.B., Cani P.D., Fauvel J., Alessi M.C.,Chamontin B., Ferriéres J.: Energy intake is associated with endotoxemiain apparently healthy men. Am. J. Clin. Nutr., 2008; 87: 1219-1223
Google Scholar - 2. Amyot J., Semache M., Ferdaoussi M., Fontes G., Poitout V.: Lipopolisacharidesimpair insulin gene expression in isolated isletsof Langerhans via Toll-like receptor-4 and NF-κB signalling. PLoSOne, 2012; 7: e36200
Google Scholar - 3. Andreasen A.S., Larsen N., Pedersen-Skowsquaard T., Berg R.M.,Moller K., Svendsen K.D., Jakobsen M., Pedersen B.K.: Effects of Lactobacillusacidophilus NCFM on insulin sensitivity and the systemicinflammatory response in human subjects. Br. J. Nutr., 2010;104: 1831-1838
Google Scholar - 4. Backhed F., Ding H., Wang T., Hooper LV., Koh G.Y., Nagy A., SemenkovichC.F., Gordon J.I.: Thegut microbiota as an environmentalfactor that regulates fat storage. Proc. Natl. Acad. Sci. USA, 2004;101: 15718-15723
Google Scholar - 5. Backhed F., Ley R.E., Sonnenburg J.L., Peterson D.A., Gordon J.I.:Host-bacterial mutualism in the human intestine. Science, 2005;307: 1915-1920
Google Scholar - 6. Backhed F., Manchester J.K., Semenkovich C.F., Gordon J.I.: Mechanismsunderlying the resistance to diet-induced obesity in germ-freemice. Proc. Natl. Acad. Sci. USA, 2007; 104: 979-984
Google Scholar - 7. Berg R.D.: The indigenous gastrointestinal microflora. TrendsMicrobiol., 1996; 4: 430-435
Google Scholar - 8. Caesar R., Reigstad C.S., Bäckhed H.K., Reinhardt C., Ketonen M.,Lunden G.Ö., Cani P.D., Bäckhed F.: Gut-derived lipopolisaccharideaugments adipose macrophage accumulation but is not essentialfor impaired glucose or insulin tolerance in mice. Gut, 2012; 61:1701-1707
Google Scholar - 9. Cani P.D., Delzenne N.M.: Involvement of the gut microbiota inthe development of low grade inflammation associated with obesity:focus on this neglected partner. Acta Gastroenterol. Belg., 2010;73: 267-269
Google Scholar - 10. Cani P.D., Dewever C., Delzenne N.M.: Inulin-type fructants modulategastrointestinal peptides in appetite regulation (glucagon-likepeptide and ghrelin) in rats. Br. J. Nutr., 2004; 92: 521-525
Google Scholar - 11. Cani P.D., Hoste S., Guiot Y., Delzenne N.M.: Dietary non-digestiblecarbohydtates promote L-cell differentiation in the proximalcolon of rats. Br. J. Nutr., 2007; 98: 32-37
Google Scholar - 12. Cani P.D., Lecourt E., Dewulf E.M., Sohet F.M., Pachikian B.D., NaslainD., De Backer F., Neyrinck A.M., Delzenne N.M.: Gut microbiotafermentation of prebiotics increases satietogenic and incretin gutpeptide prodaction with consequences for appetite sensation andglucose response after a meal. Am. J. Clin. Nutr., 2009; 90: 1236-1243
Google Scholar - 13. Cani P.D., Neyrinck A.M., Fava F., Knauf C., Burcelin R.G., TuohyK.M., Gibson G.R., Delzenne N.M.: Selective increases of bifidobacteriain gut microflora improve high-fat-diet-induced diabetes in micethrough a mechanism associated with endotoxemia. Diabetologia,2007; 50: 2374-2383
Google Scholar - 14. Cani P.D., Neyrinck A.M., Maton N., Delzenne N.M.: Oligofructosepromotes satiety in rats fed a high-fat diet involvement of glucagon–like-peptide 1. Obes. Res., 2005; 13: 1000-1007
Google Scholar - 15. Cani P.D., Possemiers S., Van de W.T., Guiot Y., Everard A., RottierO., Geurts L., Naslain D., Neyrinck A., Lambert D.M., Muccioli G.G.,Delzenne N.M.: Changes in gut microbiota control inflammation inobese mice through a mechanism involving GLP-2-driven improvementof gut permability. Gut, 2009; 58: 1091-1103
Google Scholar - 16. Collado M.C., Isolauri E., Laitinen K., Salminen S.: Distinct compositionof gut microbiota during pregnancy in overweight and normal-weightwomen. Am. J. Clin. Nutr., 2008; 88: 894-899
Google Scholar - 17. Creely S.J., McTernan P.G., Kusminski C.M., Fisher M., Da SilvaN.F., Khanolkar M., Evans M., Harte A.L., Kumar S.: Lipopolisaccharideactivates an innate immune system response in human adiposetissue in obesity and type 2 diabetes. Am. J. Physiol. Endocrinol.Metab., 2007; 292: E740-E747
Google Scholar - 18. Deopurkar R., Ghanim H., Friedman J., Abuaysheh S., Sia CL.,Mohanty P., Viswanathan P., Chaudhuri A., Dandona P.: Differentialeffects of cream, glucose and orange juice on inflammation, endotoxin,and the expression of toll-like receptor-4 and suppressor ofcytokine signaling-3. Diabetes Care, 2010; 33: 991-997
Google Scholar - 19. De Silva A., Salem V., Long C.J., Makwana A., Newbould R.D., RabinerE.A., Ghatei M.A., Bloom S.R., Matthews P.M., Beaver J.D., DhilloW.S.: The gut hormones PYY 3-36 and GLP-12-36 amide reduce foodintake and modulate brain activity in appetite centers in humans.Cell Metab., 2011; 14: 700-706
Google Scholar - 20. Ding S., Chi M.M., Scull B.P., Rigby R., Schwerbrock N.M, MagnessS., Jobin C., Lund P.K.: High-fat diet. Bacteria interactions promoteintestinal inflammation which precedes and correlates with obesityand insulin resistance in mouse. PLoS One, 2010; 5: e12191
Google Scholar - 21. 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
Google Scholar - 22. Eckburg P.B., Bik E.M., Bernstein C.N., Purdom E., DethlefsenL., Sargent M.: Diversity of the human intestinal microbial flora.Science, 2005; 308: 1635-1638
Google Scholar - 23. Frank D.N., St Amand A.L., Feldman R.A., Boedeker E.C., HarpazN., Pace N.R.: Molecular-phylogenetic analyses of human gastrointestinalmicrobiota. Proc. Natl. Acad. Sci. USA, 2007; 104: 13780-13785
Google Scholar - 24. Furet J.P., Kong L.C., Tap J., Poitou C., Basdevant A, Bouillot J.L,Mariat D., Corthier G., Doré J., Henegar C., Rizkalla S., Clément K.:Differential adaptation of human gut microbiota to bariatric surgery-inducedweight loss: links with metabolic and low grade inflammationmarkers. Diabetes, 2010; 59: 3049-3057
Google Scholar - 25. Geurts L., Lazarevic V., Derrien M., Everard A., Van Roye M.,Knauf C., Valet P., Girard M., Muccioli G.G., François P., de Vos W.M.,Schrenzel J., Delzenne N.M., Cani P.D.: Altered gut microbiota andendocannabinoid system tone in obese and diabetic leptin-resistantmice: impact on apelin regulation in adipose tissue. Front. Microbiol.,2011; 2: 149
Google Scholar - 26. Gill S.R., Pop M., Deboy R.T., Eckburg P.B., Turnbaugh P.J., SamuelB.S., Gordon J.I., Relman D.A., Fraser-Liggett C.M., Nelson K.E.:Metagenomic analysis of the human distal gut microbiome. Science,2006; 6: 4246-4258
Google Scholar - 27. Girardin S.E., Boneca I.G., Carneiro L.A., Antignac A., JéhannoM., Viala J., Tedin K., Taha M.K., Labigne A., Zähringer U., Coyle A.J.,DiStefano P.S., Bertin J., Sansonetti P.J., Philpott D.J.: Nod1 detectsa unique muropeptide from gram-negative bacterial peptidoglycan.Science, 2003; 300: 1584-1587
Google Scholar - 28. Hajer G.R., van Haeften T.W., Visseren F.L.: Adipose tissue dysfunctionin obesity, diabetes, and vascular diseases. Eur. Heart J.,2008; 29: 2959-2971
Google Scholar - 29. Hong Y.H., Nishimura Y., Hishikawa D., Tsuzuki H., Miyahara H.,Gotoh C., Choi K.C., Feng D.D., Chen C., Lee H.G., Katoh K., Roh S.G.,Sasaki S.: Acetate and propionate short chain fatty acids stimulateadipogenesis via GPCR43. Endocrinology, 2005; 146: 5092-5099
Google Scholar - 30. Huang X.F., Yu Y., Beck E.J., South T., Li Y., Batterham M.J., TapsellL.C., Chen J.: Diet high in oat β-glucan activates the gut-hypothalamic(PYY 3-36 – NPY) axis and increases satiety in diet-induced obesityin mice. Mol. Nutr. Food Res., 2011; 55: 1118-1121
Google Scholar - 31. Kadooka Y., Sato M., Imaizumi K., Ogawa A., Ikuyama K., AkaiY., Okano M., Kagoshima M., Tsuchida T.: Regulation of abdominaladiposity by probiotics (Lactobacillus gasseri SBT2055) in adultswith obese tendencies in a randomized controlled trial. Eur. J. Clin.Nutr., 2010; 64: 636-643
Google Scholar - 32. Kalliomaki M., Collado C.M., Salminen S., Isolauri E.: Early differencesin fecal microbiota composition in children may predictoverweight. Am. J. Clin. Nutr., 2008; 87: 534-538
Google Scholar - 33. Kocełak P., Żak-Gołąb A., Zahorska-Markiewicz B., Aptekorz M.,Zientara M., Martirosian G., Chudek J., Olszanecka-Glinianowicz M.:Resting energy expenditure and intestinal microbiota in obese andnormal weight subjects. Obes. Facts, 2012; 5 (supl. l): 128
Google Scholar - 34. Levin B.E., Keesey R.E.: Defense of differing body weight set pointsin diet-induced obese and resistant rats. Am. J. Physiol., 1998;274: R412-R419
Google Scholar - 35. 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
Google Scholar - 36. Ley R.E., Hamady M., Lozupone C., Turnbaugh P.J., Ramey R.R.,Bircher J.S., Schlegel M.L., Tucker T.A., Schrenzel M.D., Knight R.,Gordon J.I.: Evolution of mammals and their gut microbes. Science,2008; 320: 1647-1651
Google Scholar - 37. Ley R.E., Turnbaugh P.J., Klein S., Gordon J.I.: Microbial ecology:human gut microbes associated with obesity. Nature, 2006;444: 1022-1023
Google Scholar - 38. Mandard S., Zandbergen F., van Straten E., Wahli W., KuipersF., Muller M., Kersten S.: The fasting-induced adipose factor/angiopoetin-likeprotein 4 is physically associated with lipoproteinsand governs plasma lipid levels and adiposity. J. Biol. Chem., 2006;281; 934-944
Google Scholar - 39. Mathan V.I., Wiederman J., Dobkin J.F., Lindenbaum J.: Geograficdifferences in digoxin inactivation, a metabolic activity of thehuman anaerobic gut flora. Gut, 1989; 30: 971-977
Google Scholar - 40. Muccioli G.G., Naslain D., Backhed F., Reigstad C.S., Lambert D.M.,Delzenne N.M., Cani P.D.: The endocannabinoid system links gut microbiotato adipogenesis. Mol. Syst. Biol., 2010; 6: 392
Google Scholar - 41. Neish A.S.: Microbes in gastrointestinal health and disease. Gastroenterology,2009; 136: 65-80
Google Scholar - 42. Olszanecka-Glinianowicz M., Chudek J., Kocełak P., Szromek A.,Zahorska-Markiewicz B.: Body fat changes and activity of tumornecrosis factor α system – a 5-year follow-up study. Metabolism,2011; 60: 531-536
Google Scholar - 43. Olszanecka-Glinianowicz M., Zahorska-Markiewicz B., JanowskaJ., Żurakowski A.: Serum concentrations of nitric oxide, tumor necrosisfactor (TNF)-alpha and TNF soluble receptors in women withoverweight and obesity. Metabolism, 2004; 53: 1268-1273
Google Scholar - 44. Parnell J.A., Reimer R.A.: Weight loss during oligofructose supplementationis associated with decreased ghrelin and increasedpeptide YY in overweight and obese adults. Am. J. Clin. Nutr., 2009;89: 1751-1759
Google Scholar - 45. Qin J., Li R., Raes J., Arumugam M., Burgdorf K.S., Manichanh C.,Nielsen T., Pons N., Levenez F., Yamada T., Mende D.R., Li J., Xu J., LiS., Li D. i wsp.: A human gut microbial gene catalogue establishedby metagenomic sequencing. Nature, 2010; 464: 59-65
Google Scholar - 46. Raoult D.: Probiotics and obesity: a link? Nat. Rev. Microbiol.,2009; 7: 616
Google Scholar - 47. Samuel B.S., Shaito A., Motoike T., Rey F.E., Backhed F., ManchesterJ.K., Hammer R.E., Williams S.C., Crowley J., YanagisawaM., Gordon J.I.: Effects of the gut microbiota on host adiposity aremodulated by the short-chain fatty-acid binding G protein-coupledreceptor, Gpr41. Proc. Natl. Acad. Sci. USA, 2008; 105: 16767-16772
Google Scholar - 48. Schwiertz A., Taras D., Schafer K., Beijer S., Bos N.A., Donus C.,Hardt P.D.: Microbiota and SCFA in lean and overweight healthysubjects. Obesity, 2010; 18: 190-195
Google Scholar - 49. Takeda K., Kaisho T., Akira S.: Toll-like receptors. Annu. Rev.Immunol., 2003; 21: 335-376
Google Scholar - 50. Tappy L.: Metabolic consequences of overfeeding in humans.Curr. Opin. Clin. Nutr. Metab. Care, 2004; 7: 623-628
Google Scholar - 51. Thomas C., Gioiello A., Noriega L., Strehle A, Oury J., Rizzo G.,Macchiarulo A., Yamamoto H., Mataki C., Pruzanski M., Pellicciari R.,Auwerx J., Schoonjans K.: TGR5-mediated bile acid sensing controlsglucose homeostasis. Cell Metab., 2009; 10: 167-177
Google Scholar - 52. Trayhurn P., Beattie J.H.: Physiological role of adipose tissue:white adipose tissue as an endocrine and secretory organ. Proc.Nutr. Soc., 2001; 60: 329-339
Google Scholar - 53. Turnbaugh P.J., Ley R.E., Mahowald M.A., Magrini V., Mardis E.R.,Gordon J.I.: An obesity-associated gut microbiome with increasedcapacity for energy harvest. Nature, 2006; 444: 1027-1031
Google Scholar - 54. Verhoef S.P., Meyers D., Westerntrap K.R.: Effects of oligofructoseon appetite profile, glucagon-like peptide 1 and peptide YY 3-36concentrations and energy intake. Br. J. Nutr., 2011; 106: 1757-1762
Google Scholar - 55. Weisberg S.P., McCann D., Desai M., Rosenbaum M., Leibel R.L.,Ferrante A.W. Jr.: Obesity is associated with macrophage accumulationin adipose tissue. J. Clin. Invest., 2003;112: 1796-1808
Google Scholar - 56. Wolever T.M., Spadafora P., Eshuis H.: Interactions betweencolonic acetate and propionate in humans. Am. J. Clin. Nutr., 1991;53: 681-687
Google Scholar - 57. Zahorska-Markiewicz B., Janowska J., Olszanecka-GlinianowiczM., Zurakowski A.: Serum concentrations of TNF-alpha and solubleTNF-alpha receptors in obesity. Int. J. Obes. Relat. Metab. Disord.,2000; 24: 1392-1395
Google Scholar - 58. Zoetendal E.G., Rajilic-Stojanovic M., de Vos W.M.: High-throughputdiversity and functionality analysis of the gastrointestinaltract microbiota. Gut, 2008; 57: 1605-1615
Google Scholar