Skip to main content
SpringerLink
Log in

Gut Microbiota and the Pathogenesis of Insulin Resistance

  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Several reviews recently explored how the gut microbiota was able to control host energy metabolism, and thereby the development of adiposity. In this review, we focused on the state of the art that supports a link between the gut microbiota composition and activity, and the management of glycemia associated with overweight and diabetes. Several microbial-derived compounds are related to disturbances of glucose homeostasis including the gram-negative–derived lipopolysaccharides. Some nutrients with prebiotic properties, which escape the digestion in the upper part of the gut, modify the composition of the gut microbiota in favor of bacteria that could play a beneficial role on glucose homeostasis, namely by modulating the endocrine function of the gut, and by reinforcing the gut barrier. Adequate intervention studies in diabetic patients are required to assess the relevance of those experimental data for human health.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Cani PD, Delzenne NM: The gut microbiome as therapeutic target. Pharmacol Ther 2011. doi:10.1016/J.PHARMTHERA.2011.01.012

  2. Jia W, Li H, Zhao L, Nicholson JK. Gut microbiota: a potential new territory for drug targeting. Nat Rev Drug Discov. 2008;7:123–9.

    Article  PubMed  CAS  Google Scholar 

  3. • Backhed F, Crawford PA. Coordinated regulation of the metabolome and lipidome at the host-microbial interface. Biochim Biophys Acta. 2010;1801:240–5. This paper reviews the collected data related to the metabolomic approach to evaluate microbial-host interactions.

    PubMed  Google Scholar 

  4. Kovacs A, Ben-Jacob N, Tayem H, et al. Genotype is a stronger determinant than sex of the mouse gut microbiota. Microb Ecol. 2011;61:423–8.

    Article  PubMed  Google Scholar 

  5. Ley RE. Obesity and the human microbiome. Curr Opin Gastroenterol. 2010;26:5–11.

    Article  PubMed  Google Scholar 

  6. Cani PD, Delzenne NM. Interplay between obesity and associated metabolic disorders: new insights into the gut microbiota. Curr Opin Pharmacol. 2009;9:737–43.

    Article  PubMed  CAS  Google Scholar 

  7. Backhed F, Ding H, Wang T, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA. 2004;101:15718–23.

    Article  PubMed  Google Scholar 

  8. Backhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice 1. Proc Natl Acad Sci USA. 2007;104:979–84.

    Article  PubMed  CAS  Google Scholar 

  9. Diamant M, Blaak EE, de Vos WM: Do nutrient-gut-microbiota interactions play a role in human obesity, insulin resistance and type 2 diabetes? Obes Rev 2010.

  10. Rabot S, Membrez M, Bruneau A, et al. Germ-free C57BL/6 J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolism. FASEB J. 2010;24:4948–59.

    Article  PubMed  CAS  Google Scholar 

  11. Fleissner CK, Huebel N, Abd El-Bary MM, et al. Absence of intestinal microbiota does not protect mice from diet-induced obesity. Br J Nutr. 2010;104:919–29.

    Article  PubMed  CAS  Google Scholar 

  12. •• Vijay-Kumar M, Aitken JD, Carvalho FA, et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science. 2010;328:228–31. This is one of the key papers showing the transferability of the diabetic phenotype by inoculation of the gut microbiota to germ-free mice.

    Article  PubMed  CAS  Google Scholar 

  13. Delzenne NM, Cani PD. Nutritional modulation of gut microbiota in the context of obesity and insulin resistance: Potential interest of prebiotics. Int Dairy J. 2010;20:277–80.

    Article  CAS  Google Scholar 

  14. Cani PD, Bibiloni R, Knauf C, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008;57:1470–81.

    Article  PubMed  CAS  Google Scholar 

  15. Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56:1761–72.

    Article  PubMed  CAS  Google Scholar 

  16. Shi H, Kokoeva MV, Inouye K, et al. TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest. 2006;116:3015–25.

    Article  PubMed  CAS  Google Scholar 

  17. •• Basu S, Haghiac M, Surace P, et al. Pregravid obesity associates with increased maternal endotoxemia and metabolic inflammation. Obesity (Silver Spring). 2011;19:476–82. This is interesting data relating the inflammation status and microbial changes upon pregnancy and fat mass development.

    Article  CAS  Google Scholar 

  18. Creely SJ, McTernan PG, Kusminski CM, et al. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am J Physiol Endocrinol Metab. 2007;292:E740–7.

    Article  PubMed  CAS  Google Scholar 

  19. Sun L, Yu Z, Ye X, et al. A marker of endotoxemia is associated with obesity and related metabolic disorders in apparently healthy Chinese. Diab Care. 2010;33:1925–32.

    Article  CAS  Google Scholar 

  20. Cani PD, Neyrinck AM, Fava F, et al. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007;50:2374–83.

    Article  PubMed  CAS  Google Scholar 

  21. Amar J, Burcelin R, Ruidavets JB, et al. Energy intake is associated with endotoxemia in apparently healthy men. Am J Clin Nutr. 2008;87:1219–23.

    PubMed  CAS  Google Scholar 

  22. Ghanim H, Abuaysheh S, Sia CL, et al. Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance. Diab Care. 2009;32:2281–7.

    Article  CAS  Google Scholar 

  23. Erridge C, Attina T, Spickett CM, Webb DJ. A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation. Am J Clin Nutr. 2007;86:1286–92.

    PubMed  CAS  Google Scholar 

  24. Cani PD, Possemiers S, Van de WT, et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut. 2009;58:1091–103.

    Article  PubMed  CAS  Google Scholar 

  25. • Muccioli GG, Naslain D, Backhed F, et al. The endocannabinoid system links gut microbiota to adipogenesis. Mol Syst Biol. 2010;6:392. This is a paper describing the implication of the endocannabinoid system in the intestine and in the adipose tissue in the host response toward gut microbiota.

    Article  PubMed  Google Scholar 

  26. de La Serre CB, Ellis CL, Lee J, et al. Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation. Am J Physiol Gastrointest Liver Physiol. 2010;299:G440–8.

    Article  Google Scholar 

  27. Le PE, Loison C, Struyf S, et al. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation 1. J Biol Chem. 2003;278:25481–9.

    Article  Google Scholar 

  28. Samuel BS, Shaito A, Motoike T, 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;105:16767–72.

    Article  PubMed  CAS  Google Scholar 

  29. Hong YH, Nishimura Y, Hishikawa D, et al. Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. Endocrinology. 2005;146:5092–9.

    Article  PubMed  CAS  Google Scholar 

  30. • Al-Lahham SH, Peppelenbosch MP, Roelofsen H, et al. Biological effects of propionic acid in humans; metabolism, potential applications and underlying mechanisms. Biochim Biophys Acta. 2010;1801:1175–83. This is a complete review of the state of the art concerning the metabolic regulation by propionate.

    PubMed  CAS  Google Scholar 

  31. Gao Z, Yin J, Zhang J, et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes. 2009;58:1509–17.

    Article  PubMed  CAS  Google Scholar 

  32. Neyrinck AM, Delzenne NM. Potential interest of gut microbial changes induced by non-digestible carbohydrates of wheat in the management of obesity and related disorders. Curr Opin Clin Nutr Metab Care. 2010;13:722–8.

    Article  PubMed  CAS  Google Scholar 

  33. Ley RE, Backhed F, Turnbaugh P, et al. Obesity alters gut microbial ecology. Proc Natl Acad Sci USA. 2005;102:11070–5.

    Article  PubMed  CAS  Google Scholar 

  34. Duncan SH, Lobley GE, Holtrop G, et al. Human colonic microbiota associated with diet, obesity and weight loss. Int J Obes (Lond). 2008;32:1720–4.

    Article  CAS  Google Scholar 

  35. Zhang H, DiBaise JK, Zuccolo A, et al. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci USA. 2009;106:2365–70.

    Article  PubMed  CAS  Google Scholar 

  36. Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, et al. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology. 2009;137:1716–24.

    Article  PubMed  CAS  Google Scholar 

  37. Murphy EF, Cotter PD, Healy S, et al. Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut. 2010;59:1635–42.

    Article  PubMed  CAS  Google Scholar 

  38. Kalliomaki M, Collado MC, Salminen S, Isolauri E. Early differences in fecal microbiota composition in children may predict overweight. Am J Clin Nutr. 2008;87:534–8.

    PubMed  CAS  Google Scholar 

  39. Collado MC, Isolauri E, Laitinen K, Salminen S. Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. 1. Am J Clin Nutr. 2008;88:894–9.

    PubMed  CAS  Google Scholar 

  40. O’Mahony D, Murphy S, Boileau T, et al. Bifidobacterium animalis AHC7 protects against pathogen-induced NF-kappaB activation in vivo. BMC Immunol. 2010;11:63.

    Article  PubMed  Google Scholar 

  41. Schwiertz A, Taras D, Schafer K, et al. Microbiota and SCFA in lean and overweight healthy subjects. Obes Silver Spring. 2010;18:190–5.

    Article  Google Scholar 

  42. •• Luoto R, Kalliomaki M, Laitinen K, et al. Initial dietary and microbiological environments deviate in normal-weight compared to overweight children at 10 years of age. J Pediatr Gastroenterol Nutr. 2011;52:90–5. This is interesting data supporting the relevance of the changes in microbiota early in life on the occurrence of overweight and obesity.

    Article  PubMed  Google Scholar 

  43. Luoto R, Laitinen K, Nermes M, Isolauri E. Impact of maternal probiotic-supplemented dietary counselling on pregnancy outcome and prenatal and postnatal growth: a double-blind, placebo-controlled study. Br J Nutr. 2010;103:1792–9.

    Article  PubMed  CAS  Google Scholar 

  44. •• Furet JP, Kong LC, Tap J, et al. Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes. 2010;59:3049–57. This is a key paper describing the relationship between the level of F. Prausnitzii in the fecal samples of obese humans, and the development of diabetes and inflammation.

    Article  PubMed  CAS  Google Scholar 

  45. Santacruz A, Collado MC, Garcia-Valdes L, et al. Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women. Br J Nutr. 2010;104:83–92.

    Article  PubMed  CAS  Google Scholar 

  46. •• Larsen N, Vogensen FK, van den Berg FW, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One. 2010;5:e9085. This is novel data comparing the changes in gut in the profile of bacteria in diabetic and nondiabetic patients.

    Article  PubMed  Google Scholar 

  47. •• Wu X, Ma C, Han L, et al. Molecular characterisation of the faecal microbiota in patients with type II diabetes. Curr Microbiol. 2010;61:69–78. This is one of the rare data published in humans that report the changes in gut microbiota with a focus on bifidobacteria composition in diabetic patients.

    Article  PubMed  CAS  Google Scholar 

  48. Zhao X, Fritsche J, Wang J, et al. Metabonomic fingerprints of fasting plasma and spot urine reveal human pre-diabetic metabolic traits. Metabolomics. 2010;6:362–74.

    Article  PubMed  CAS  Google Scholar 

  49. Roberfroid M, Gibson GR, Hoyles L, et al. Prebiotic effects: metabolic and health benefits. Br J Nutr. 2010;104 Suppl 2:S1–63.

    Article  PubMed  CAS  Google Scholar 

  50. Cani PD, Knauf C, Iglesias MA, et al. Improvement of glucose tolerance and hepatic insulin sensitivity by oligofructose requires a functional glucagon-like Peptide 1 receptor. Diabetes. 2006;55:1484–90.

    Article  PubMed  CAS  Google Scholar 

  51. Cani PD, Lecourt E, Dewulf EM, et al. Gut microbiota fermentation of prebiotics increases satietogenic and incretin gut peptide production with consequences for appetite sensation and glucose response after a meal. Am J Clin Nutr. 2009;90:1236–43.

    Article  PubMed  CAS  Google Scholar 

  52. Kaji I, Karaki SI, Tanaka R, Kuwahara A: Density distribution of free fatty acid receptor 2 (FFA2)-expressing and GLP-1-producing enteroendocrine L cells in human and rat lower intestine, and increased cell numbers after ingestion of fructo-oligosaccharide. J Mol Histol 2010.

  53. Tarini J, Wolever TM. The fermentable fibre inulin increases postprandial serum short-chain fatty acids and reduces free-fatty acids and ghrelin in healthy subjects. Appl Physiol Nutr Metab. 2010;35:9–16.

    Article  PubMed  CAS  Google Scholar 

  54. Abrams SA, Griffin IJ, Hawthorne KM, Ellis KJ. Effect of prebiotic supplementation and calcium intake on body mass index. J Pediatr. 2007;151:293–8.

    Article  PubMed  CAS  Google Scholar 

  55. Genta S, Cabrera W, Habib N, et al. Yacon syrup: beneficial effects on obesity and insulin resistance in humans. Clin Nutr. 2009;28:182–7.

    Article  PubMed  CAS  Google Scholar 

  56. Parnell JA, Reimer RA. Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Am J Clin Nutr. 2009;89:1751–9.

    Article  PubMed  CAS  Google Scholar 

  57. Luo J, Van YM, Rizkalla SW, et al. Chronic consumption of short-chain fructooligosaccharides does not affect basal hepatic glucose production or insulin resistance in type 2 diabetics. J Nutr. 2000;130:1572–7.

    PubMed  CAS  Google Scholar 

  58. Giacco R, Clemente G, Luongo D, et al. Effects of short-chain fructo-oligosaccharides on glucose and lipid metabolism in mild hypercholesterolaemic individuals. Clin Nutr. 2004;23:331–40.

    Article  PubMed  CAS  Google Scholar 

  59. Freeland KR, Wilson C, Wolever TM. Adaptation of colonic fermentation and glucagon-like peptide-1 secretion with increased wheat fibre intake for 1 year in hyperinsulinaemic human subjects. Br J Nutr. 2010;103:82–90.

    Article  PubMed  CAS  Google Scholar 

Download references

Disclosure

Conflicts of interest: N.M. Delzenne: is a recipient of subsides from the Fonds National de la Recherche Scientifique (FNRS/FRSM) and from the “fonds spéciaux de recherche,” UCL (Université catholique de Louvain); P.D. Cani: is research associate from the FRS-FNRS (Fonds de la Recherche Scientifique, Belgique), and is a recipient of subsides from the Fonds National de la Recherche Scientifique (FNRS/FRSM) and from the “fonds spéciaux de recherche,” UCL (Université catholique de Louvain).

Author information

Authors and Affiliations

  1. Louvain Drug Research Institute, Metabolism and Nutrition Research Group, Université Catholique de Louvain, Brussels, Belgium

    Nathalie M. Delzenne & Patrice D. Cani

  2. LDRI/MNUT, UCL, Av. E. Mounier, 73, 1200, Brussels, Belgium

    Nathalie M. Delzenne

Authors
  1. Nathalie M. Delzenne
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patrice D. Cani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nathalie M. Delzenne.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Delzenne, N.M., Cani, P.D. Gut Microbiota and the Pathogenesis of Insulin Resistance. Curr Diab Rep 11, 154–159 (2011). https://doi.org/10.1007/s11892-011-0191-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11892-011-0191-1

Keywords

Search

Navigation