Pharmacogenomics and Gut Microbiota Biomarkers in Obesity

  • Margarita Aguilera
  • María Luján Jiménez-Pranteda
  • Barbara Jenko
  • Verónica Jiménez
  • Marisa Cañadas Garre


Obesity development is a dependent multifactor disease due to imbalance between energy intake and energy expenditure. This balance represents a combination of numerous variables such as behavior, diet, environment, genetics, and social structures. Complex interactions among these variables contribute to the individual differences for development of obesity which leads and allows individualizing of treatment response.

Physicians are exploring the causes and the main approaches and strategies to tailor individualized treatments based on importance of host genetic variability itself and the microbiota variability.

The chapter will be focus on omics application impact involved in clinical biomarkers differentially detected nowadays with a demonstrated impact on obese individuals, mainly those that detect host biomarkers and also gut microbiota biomarkers.

Disease biomarkers for obesity are multiple, such us immunological (inflammatory status, defined by elevated C-reactive protein and IL-6), biochemical (glucose, lipids, satiety-related hormones), microbiological (the fecal microbial composition), and genetic (Tiihonen K, Ouwehand AC, Rautonen N, Br J Nutr 103(7):1070–1078, 2010).

Genetic markers for prognosis of weight loss response are genes coding adrenergic receptors (ADBRs), uncoupling proteins (UCPs), leptin (LEP), leptin receptor (LEPR), melanocortin pathways genes (MC3R, POMC), serotonin receptor, peroxisome proliferator-activated receptor PPAR-γ-2, and genes related to cytokines (Martinez AJ, Parra DM, Santos JL et al. Asia Pac J Clin Nutr 17:119–122, 2008).

Moreover, through current literature, it is clear that variable individual composition of intestinal microbiota plays a role in energy extraction from non-digested carbohydrates in the form of production of short-chain fatty acids. The microbiota also plays a role in host metabolism by influencing and modulating host gene expression in various tissues. For this reason, a specific part of the chapter is deserved for molecular and genetics microbiota variability explanations.

Furthermore, it is suggested by several researchers that the host genetic may influence the composition of gut microbiota. The proposed genes which affect the microbiota composition are related to the immune system function and metabolism (Mathes WF, Kelly SA, Pomp D Br J Nutr 106(Suppl 1):S1–10,2011). Several studies indicate that lean and obese microbiome differ primarily in their interface with the host and in the way they interact with host metabolism, suggest the importance of host genetic control in shaping individual microbiome diversity in mammals (Benson AK, Kelly SA, Legge R, Ma F, Low SJ, Kim J, Zhang M, Oh PL, Nehrenberg D, Hua K, Kachman SD, Moriyama EN, Walter J, Peterson DA, Pomp D, Proc Natl Acad Sci U S A 107:18933–18938, 2010).


Intestinal Microbiota Nonalcoholic Fatty Liver Disease Fatty Acid Amide Hydrolase Host Metabolism Adipose Tissue Metabolism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Agarwal P, Searls DB (2008) Literature mining in support of drug discovery. Brief Bioinform 9(6):479–492, Epub 2008 Sep 27. Review. PubMed PMID: 18820304PubMedGoogle Scholar
  2. Agurs-collins T, Khoury MJ, Simon-morton D, Olster DH, Harris JR, Milner JA (2009) NIH public access. Obesity 16(Suppl 3):1–18Google Scholar
  3. Alexeyenko A, Schmitt T, Tjärnberg A, Guala D, Frings O, Sonnhammer EL (2011) Comparative interactomics with Funcoup 2.0. Nucleic Acids Res 40(Database issue):D821–D828, PMID: 22110034PubMedCentralPubMedGoogle Scholar
  4. Ament Z, Masoodi M, Griffin JL (2012) Applications of metabolomics for understanding the action of peroxisome proliferator-activated receptors (PPARs) in diabetes, obesity and cancer. Genome Med 4(4):32, PMID: 22546357PubMedCentralPubMedGoogle Scholar
  5. Andreasen CH, Stender-Petersen KL, Mogensen MS, Torekov SS, Wegner L, Andersen G, Nielsen AL, Albrechtsen A, Borch-Johnsen K, Rasmussen SS, Clausen JO, Sandbaek A, Lauritzen T, Hansen L, Jørgensen T, Pedersen O, Hansen T (2008) Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes 57(1):95–101, PMID:17942823PubMedGoogle Scholar
  6. Angelakis E, Bastelica D, Ben Amara A, El Filali A, Dutour A, Mege JL, Alessi MC, Raoult D (2012) An evaluation of the effects of Lactobacillus ingluviei on body weight, the intestinal microbiome and metabolism in mice. Microb Pathog 52(1):61–68, PMID: 22020311PubMedGoogle Scholar
  7. Bäckhed F, Crawford PA (2010) Coordinated regulation of the metabolome and lipidome at the host-microbial interface. Biochim Biophys Acta – Mol Cell Biol Lipids 1801:240–245Google Scholar
  8. Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI (2004) The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A 101:15718–15723PubMedCentralPubMedGoogle Scholar
  9. Baessler A, Hasinoff MJ, Fischer M, Reinhard W, Sonnenberg GE, Olivier M, Erdmann J, Schunkert H, Doering A, Jacob HJ, Comuzzie AG, Kissebah AH, Kwitek AE (2005) Genetic linkage and association of the growth hormone secretagogue receptor(ghrelin receptor) gene in human obesity. Diabetes 54(1):259–267, PMID: 15616037PubMedCentralPubMedGoogle Scholar
  10. Baretić M (2012) Targets for medical therapy in obesity. Dig Dis 30(2):168–172, PMID: 22722433PubMedGoogle Scholar
  11. Benson AK, Kelly SA, Legge R, Ma F, Low SJ, Kim J, Zhang M, Oh PL, Nehrenberg D, Hua K, Kachman SD, Moriyama EN, Walter J, Peterson DA, Pomp D (2010) Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors. Proc Natl Acad Sci U S A 107:18933–18938PubMedCentralPubMedGoogle Scholar
  12. Benzinou M, Creemers JW, Choquet H, Lobbens S, Dina C, Durand E, Guerardel A, Boutin P, Jouret B, Heude B, Balkau B, Tichet J, Marre M, Potoczna N, Horber F, Le Stunff C, Czernichow S, Sandbaek A, Lauritzen T, Borch-Johnsen K, Andersen G, Kiess W, Körner A, Kovacs P, Jacobson P, Carlsson LM, Walley AJ, Jørgensen T, Hansen T, Pedersen O, Meyre D, Froguel P (2008) Common nonsynonymous variants in PCSK1 confer risk of obesity. Nat Genet 40(8):943–945, PMID: 18604207PubMedGoogle Scholar
  13. Birzele F, Fässler S, Neubauer H, Hildebrandt T, Hamilton BS (2012) Analysis of the transcriptome of differentiating and non-differentiating preadipocytes from rats and humans by next generation sequencing. Mol Cell Biochem 369(1–2):175–181, PMID: 22773307PubMedGoogle Scholar
  14. Brignardello J, Morales P, Diaz E, Romero J, Brunser O, Gotteland M (2010) Pilot study: alterations of intestinal microbiota in obese humans are not associated with colonic inflammation or disturbances of barrier function. Aliment Pharmacol Ther 32(11–12):1307–1314PubMedGoogle Scholar
  15. Brönner G, Sattler AM, Hinney A, Soufi M, Geller F, Schäfer H, Maisch B, Hebebrand J, Schaefer JR (2006) The 103I variant of the melanocortin 4 receptor is associated with low serum triglyceride levels. J Clin Endocrinol Metab 91(2):535–538, PMID:16278267PubMedGoogle Scholar
  16. Caesar R, Fåk F, Bäckhed F (2010) Effects of gut microbiota on obesity and atherosclerosis via modulation of inflammation and lipid metabolism. J Intern Med 268:320–328PubMedGoogle Scholar
  17. Canani RB, Costanzo MD, Leone L, Bedogni G, Brambilla P, Cianfarani S, Nobili V, Pietrobelli A, Agostoni C (2011) Epigenetic mechanisms elicited by nutrition in early life. Nutr Res Rev 24(2):198–205, PMID: 22008232PubMedGoogle Scholar
  18. 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, Ferrières J, Tanti JF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56:1761–1772PubMedGoogle Scholar
  19. Clément K (2011 Sep) Bariatric surgery, adipose tissue and gut microbiota. Int J Obes (Lond) 35(Suppl 3):S7–S15. doi: 10.1038/ijo.2011.141, Review. PubMed PMID: 21912389Google Scholar
  20. Chen HH, Lee WJ, Wang W, Huang MT, Lee YC, Pan WH (2007) Ala55Val polymorphism on UCP2 gene predicts greater weight loss in morbidly obese patients undergoing gastric banding. Obes Surg 17(7):926–933, PMID: 17894153PubMedGoogle Scholar
  21. Choi SH, Kwak SH, Lee Y, Moon MK, Lim S, Park YJ, Jang HC, Kim MS (2011) Plasma vaspin concentrations are elevated in metabolic syndrome in men and are correlated with coronary atherosclerosis in women. Clin Endocrinol (Oxf) 75(5):628–635. doi: 10.1111/j.1365-2265.2011.04095.x, PubMed PMID: 21545478Google Scholar
  22. Choquet H, Meyre D (2010) Genomic insights into early-onset obesity. Genome Med 2(6):36PubMedCentralPubMedGoogle Scholar
  23. Colagiuri S (2010) Diabesity: therapeutic options. Diabetes Obes Metab 12(6):463–473, PMID: 20518802PubMedGoogle Scholar
  24. Cuda C, Badawi A, Karmali M, El-Sohemy A (2011) Polymorphisms in Toll-like receptor 4 are associated with factors of the metabolic syndrome and modify the association between dietary saturated fat and fasting high-density lipoprotein cholesterol. Metabolism 60(8):1131–1135, PMID: 21306745PubMedGoogle Scholar
  25. Delahanty RJ, Beeghly-Fadiel A, Xiang YB, Long J, Cai Q, Wen W, Xu WH, Cai H, He J, Gao YT, Zheng W, Shu XO (2011) Association of obesity-related genetic variants with endometrial cancer risk: a report from the Shanghai Endometrial Cancer Genetics Study. Am J Epidemiol 174(10):1115–1126. doi  10.1093/aje/kwr233. Epub 5 Oct 2011. PubMed PMID: 21976109; PubMed Central PMCID: PMC3246689Google Scholar
  26. Delzenne NM, Neyrinck AM, Cani PD (2011) Modulation of the gut microbiota by nutrients with prebiotic properties: consequences for host health in the context of obesity and metabolic syndrome. Microb Cell Fact 10(Suppl 1):S10, PMID: 21995448PubMedCentralPubMedGoogle Scholar
  27. Dhiman N, Ovsyannikova IG, Vierkant RA, Ryan JE, Pankratz VS, Jacobson RM, Poland GA (2008) Associations between SNPs in toll-like receptors and related intracellular signaling molecules and immune responses to measles vaccine: preliminary results. Vaccine 26(14):1731–1736, PMID: 18325643PubMedCentralPubMedGoogle Scholar
  28. Diamant M, Blaak EE, de Vos WM (2011) Do nutrient-gut-microbiota interactions play a role in human obesity, insulin resistance and type 2 diabetes? Obes Rev 12(4):272–281. doi: 10.1111/j.1467-789X.2010.00797.x. Epub 26 Aug 2010. Review. PubMed PMID: 20804522Google Scholar
  29. Dimitrov DV (2011) The human gutome: nutrigenomics of the host-microbiome interactions. OMICS. 15(7–8):419–430. doi: 10.1089/omi.2010.0109. Epub 1 Dec 2010. Review. PubMed PMID: 21121704
  30. Dina C, Meyre D, Samson C, Tichet J, Marre M, Jouret B, Charles MA, Balkau B, Froguel P (2007a) Comment on “A common genetic variant is associated with adult and childhood obesity”. Science 315(5809):187, PMID:17218508PubMedGoogle Scholar
  31. Dina C, Meyre D, Gallina S, Durand E, Körner A, Jacobson P et al (2007b) Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 39(6):724–726PubMedGoogle Scholar
  32. Do R, Bailey SD, Desbiens K, Belisle A, Montpetit A, Bouchard C, Pérusse L, Vohl MC, Engert JC (2008) Genetic variants of FTO influence adiposity, insulin sensitivity, leptin levels, and resting metabolic rate in the Quebec Family Study. Diabetes 57(4):1147–1150, PMID: 18316358PubMedGoogle Scholar
  33. El-Sayed Moustafa JS, Eleftherohorinou H, de Smith AJ, Andersson-Assarsson JC, Alves AC, Hadjigeorgiou E, Walters RG, Asher JE, Bottolo L, Buxton JL, Sladek R, Meyre D, Dina C, Visvikis-Siest S, Jacobson P, Sjöström L, Carlsson LM, Walley A, Falchi M, Froguel P, Blakemore AI, Coin LJ (2012) Novel association approach for variable number tandem repeats (VNTRs) identifies DOCK5 as a susceptibility gene for severe obesity. Hum Mol Genet 21(16):3727–2738. doi: 10.1093/hmg/dds187. Epub 16 May 2012. PubMed PMID: 22595969; PubMed Central PMCID: PMC3406755
  34. Fenech M, El-Sohemy A, Cahill L, Ferguson L, French TA, Tai ES, Milner J, Koh WP, Xie L, Zucker M, Buckley M, Cosgrove L, Lockett T, Fung KY, Head R (2011) Nutrigenetics and nutrigenomics: viewpoints on the current status and applications in nutrition research and practice. J Nutrigenet Nutrigenomics 28(4):69–89Google Scholar
  35. Ferguson LR, Shelling AN, Lauren D, Heyes JA, McNabb WC (2007) Nutrigenomics and gut health. Mutat Res 622:1–6PubMedGoogle Scholar
  36. Ferrer M, Ruiz A, Lanza F, Haange SB, Oberbach A, Till H, Bargiela R, Campoy C, Segura MT, Richter M, von Bergen M, Seifert J, Suarez A (2013) Microbiota from the distal guts of lean and obese adolescents exhibit partial functional redundancy besides clear differences in community structure. Environ Microbiol 15(1):211–226. doi: 10.1111/j.1462-2920.2012.02845.x, PubMed PMID: 22891823PubMedGoogle Scholar
  37. Florez H, Castillo-Florez S (2012) Beyond the obesity paradox in diabetes: fitness, fatness, and mortality. JAMA 308(6):619–620. doi: 10.1001/jama.2012.9776, PubMed PMID: 22871873PubMedGoogle Scholar
  38. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Smith GD, Hattersley AT, McCarthy MI (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316(5826):889–894, PMID: 17434869PubMedCentralPubMedGoogle Scholar
  39. Grasso P (2011) Novel approaches to the treatment of obesity and type 2 diabetes mellitus: bioactive leptin-related synthetic peptide analogs. Recent Pat Endocr Metab Immune Drug Discov 5(3):163–175, PMID: 21913885PubMedGoogle Scholar
  40. Grau K, Hansen T, Holst C, Astrup A, Saris WH, Arner P, Rössner S, Macdonald I, Polak J, Oppert JM, Langin D, Martinez JA, Pedersen O, Sørensen TI (2009) Macronutrient-specific effect of FTO rs9939609 in response to a 10-week randomized hypo-energetic diet among obese Europeans. Int J Obes (Lond) 33(11):1227–1234, PMID: 19687793Google Scholar
  41. Greenblum S, Turnbaugh PJ, Borenstein E (2012) Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease. Proc Natl Acad Sci U S A 109(2):594–599, PMID: 22184244PubMedCentralPubMedGoogle Scholar
  42. Grudell AB, Sweetser S, Camilleri M, Eckert DJ, Vazquez-Roque MI, Carlson PJ, Burton DD, Braddock AE, Clark MM, Graszer KM, Kalsy SA, Zinsmeister AR (2008) A controlled pharmacogenetic trial of sibutramine on weight loss and body composition in obese or overweight adults. Gastroenterology 135(4):1142–1154, PMID: 18725220PubMedCentralPubMedGoogle Scholar
  43. Hahn S, Frey UH, Siffert W, Tan S, Mann K, Janssen OE (2006) The CC genotype of the GNAS T393C polymorphism is associated with obesity and insulin resistance in women with polycystic ovary syndrome. Eur J Endocrinol 155(5):763–770, PMID: 17062894PubMedGoogle Scholar
  44. Harris K, Kassis A, Major G, Chou CJ (2012) Is the gut microbiota a new factor contributing to obesity and its metabolic disorders? J Obes 879151Google Scholar
  45. Hawn TR, Verbon A, Lettinga KD, Zhao LP, Li SS, Laws RJ, Skerrett SJ, Beutler B, Schroeder L, Nachman A, Ozinsky A, Smith KD, Aderem A (2003) A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires’ disease. J Exp Med 198(10):1563–1572, PMID: 14623910PubMedCentralPubMedGoogle Scholar
  46. Heid IM, Vollmert C, Hinney A, Döring A, Geller F, Löwel H, Wichmann HE, Illig T, Hebebrand J, Kronenberg F, KORA Group (2005) Association of the 103I MC4R allele with decreased body mass in 7937 participants of two population based surveys. J Med Genet 42(4):e21, PMID: 15805150PubMedCentralPubMedGoogle Scholar
  47. Herbert A, Gerry NP, McQueen MB, Heid IM, Pfeufer A, Illig T, Wichmann HE, Meitinger T, Hunter D, Hu FB, Colditz G, Hinney A, Hebebrand J, Koberwitz K, Zhu X, Cooper R, Ardlie K, Lyon H, Hirschhorn JN, Laird NM, Lenburg ME, Lange C, Christman MF (2006) A common genetic variant is associated with adult and childhood obesity. Science 312(5771):279–283, PMID: 16614226PubMedGoogle Scholar
  48. Hofker M, Wijmenga C (2009) A supersized list of obesity genes. Nat Genet 41(2):139–140, PMID: 19174833PubMedGoogle Scholar
  49. Hsiao DJ, Wu LS, Huang SY, Lin E (2009) Weight loss and body fat reduction under sibutramine therapy in obesity with the C825T polymorphism in the GNB3 gene. Pharmacogenet Genomics 19(9):730–733, PMID: 19687782PubMedGoogle Scholar
  50. Hsiao TJ, Wu LS, Hwang Y, Huang SY, Lin E (2010) Effect of the common -866G/A polymorphism of the uncoupling protein 2 gene on weight loss and body composition under sibutramine therapy in an obese Taiwanese population. Mol Diagn Ther 14(2):101–106, PMID: 20359253PubMedGoogle Scholar
  51. Hu Y, Ehli EA, Hudziak JJ, Davies GE (2012) Berberine and evodiamine influence serotonin transporter (5-HTT) expression via the 5-HTT-linked polymorphic region. Pharmacogenomics J 12(5):372–378. doi: 10.1038/tpj.2011.24. Epub 7 June 2011. PubMed PMID: 21647174Google Scholar
  52. Jeong YH, Kim MC, Ahn EK, Seol SY, Do EJ, Choi HJ, Chu IS, Kim WJ, Kim WJ, Sunwoo Y, Leem SH (2007) Rare exonic minisatellite alleles in MUC2 influence susceptibility to gastric carcinoma. PLoS One 2(11):e1163, PMID: 18000536PubMedCentralPubMedGoogle Scholar
  53. Ji B, Ernest B, Gooding JR, Das S, Saxton AM, Simon J, Dupont J, Métayer-Coustard S, Campagna SR, Voy BH (2012) Transcriptomic and metabolomic profiling of chicken adipose tissue in response to insulin neutralization and fasting. BMC Genomics 13(1):441, PMID: 22938590PubMedCentralPubMedGoogle Scholar
  54. Katoh M, Katoh M (2007) AP1- and NF-kappaB-binding sites conserved among mammalian WNT10B orthologs elucidate the TNFalpha-WNT10B signaling loop implicated in carcinogenesis and adipogenesis. Int J Mol Med 19(4):699–703, PubMed PMID: 17334647PubMedGoogle Scholar
  55. Kelly AS, Bergenstal RM, Gonzalez-Campoy JM, Katz H, Bank AJ (2012) Effects of exenatide vs. metformin on endothelial function in obese patients with pre-diabetes: a randomized trial. Cardiovasc Diabetol 11:64, PMID: 22681705PubMedCentralPubMedGoogle Scholar
  56. Klenke S, Siffert W (2011) SNPs in genes encoding G proteins in pharmacogenetics. Pharmacogenomics 12(5):633–654, PMID: 21619427PubMedGoogle Scholar
  57. Kolz M, Baumert J, Müller M, Khuseyinova N, Klopp N, Thorand B, Meisinger C, Herder C, Koenig W, Illig T (2008) Association between variations in the TLR4 gene and incident type 2 diabetes is modified by the ratio of total cholesterol to HDL-cholesterol. BMC Med Genet 9:9, PMID: 18298826PubMedCentralPubMedGoogle Scholar
  58. Kristiansson K, Perola M, Tikkanen E, Kettunen J, Surakka I, Havulinna AS, Stancáková A, Barnes C, Widen E, Kajantie E, Eriksson JG, Viikari J, Kähönen M, Lehtimäki T, Raitakari OT, Hartikainen AL, Ruokonen A, Pouta A, Jula A, Kangas AJ, Soininen P, Ala-Korpela M, Männistö S, Jousilahti P, Bonnycastle LL, Järvelin MR, Kuusisto J, Collins FS, Laakso M, Hurles ME, Palotie A, Peltonen L, Ripatti S, Salomaa V (2012) Genome-wide screen for metabolic syndrome susceptibility Loci reveals strong lipid gene contribution but no evidence for common genetic basis for clustering of metabolic syndrome traits. Circ Cardiovasc Genet 5(2):242–249, PMID: 22399527PubMedCentralPubMedGoogle Scholar
  59. Kumar V (2011) Omics and literature mining. Methods Mol Biol 719:457–477, PMID: 21370097PubMedGoogle Scholar
  60. Lakhan SE, Kirchgessner A (2011) Gut microbiota and sirtuins in obesity-related inflammation and bowel dysfunction. J Transl Med 9(1):202PubMedCentralPubMedGoogle Scholar
  61. Lasky-Su J, Lyon HN, Emilsson V, Heid IM, Molony C, Raby BA, Lazarus R, Klanderman B, Soto-Quiros ME, Avila L, Silverman EK, Thorleifsson G, Thorsteinsdottir U, Kronenberg F, Vollmert C, Illig T, Fox CS, Levy D, Laird N, Ding X, McQueen MB, Butler J, Ardlie K, Papoutsakis C, Dedoussis G, O’Donnell CJ, Wichmann HE, Celedón JC, Schadt E, Hirschhorn J, Weiss ST, Stefansson K, Lange C (2008) On the replication of genetic associations: timing can be everything! Am J Hum Genet 82(4):849–858, PMID: 18387595PubMedCentralPubMedGoogle Scholar
  62. Lehr S, Hartwig S, Sell H (2011) Adipokines: a treasure trove for the discovery of biomarkers for metabolic disorders. Proteomics Clin Appl 6(1–2):91–101, PMID: 22213627PubMedGoogle Scholar
  63. Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A 102:11070–11075PubMedCentralPubMedGoogle Scholar
  64. Ley RE, Turnbaugh PJ, Klein S, Gordon JI (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444:1022–1023PubMedGoogle Scholar
  65. Li S, Zhao JH, Luan J, Ekelund U, Luben RN, Khaw KT et al (2010) Physical activity attenuates the genetic predisposition to obesity in 20,000 men and women from EPIC-Norfolk prospective population study. PLoS Med 7:e1000332PubMedCentralPubMedGoogle Scholar
  66. Liu Y, Zhang C, Zhao L, Nardini C (2010) Adapting functional genomic tools to metagenomic analyses: investigating the role of gut bacteria in relation to obesity. Brief Funct Genomics 9(5–6):355–361, PMID: 21266343PubMedCentralPubMedGoogle Scholar
  67. Li-Wan-Po A, Farndon P (2011) Barking up the wrong genome-we are not alone. J Clin Pharm Ther 36(2):125–127, PMID: 21366639PubMedGoogle Scholar
  68. Loos RJ, Barroso I, O’rahilly S, Wareham NJ (2007) Comment on “A common genetic variant is associated with adult and childhood obesity”. Science 315(5809):187, PMID: 17218509PubMedCentralPubMedGoogle Scholar
  69. Maccaferri S, Biagi E, Brigidi P (2011) Metagenomics: key to human gut microbiota. Dig Dis 29(6):525–530, PMID: 22179207PubMedGoogle Scholar
  70. Marín F, Bonet C, Muñoz X, García N, Pardo ML, Ruiz-Liso JM, Alonso P, Capellà G, Sanz-Anquela JM, González CA, Sala N (2012) Genetic variation in MUC1, MUC2 and MUC6 genes and evolution of gastric cancer precursor lesions in a long-term follow-up in a high-risk area in Spain. Carcinogenesis 33(5):1072–1080, PMID: 22402132PubMedGoogle Scholar
  71. Martinez AJ, Parra DM, Santos JL et al (2008) Genotype-dependent response to energy-restricted diets in obese subjects: towards personalized nutrition. Asia Pac J Clin Nutr 17:119–122PubMedGoogle Scholar
  72. Mathes WF, Kelly SA, Pomp D (2011) Advances in comparative genetics: influence of genetics on obesity. Br J Nutr 106(Suppl 1):S1–S10, PMID: 22005399PubMedGoogle Scholar
  73. Michelsen KS, Arditi M (2007) Toll-like receptors and innate immunity in gut homeostasis and pathology. Curr Opin Hematol 14(1):48–54, PMID: 17133100PubMedGoogle Scholar
  74. Moehle C, Ackermann N, Langmann T, Aslanidis C, Kel A, Kel-Margoulis O, Schmitz-Madry A, Zahn A, Stremmel W, Schmitz G (2006) Aberrant intestinal expression and allelic variants of mucin genes associated with inflammatory bowel disease. J Mol Med 84(12):1055–1066, PMID: 17058067PubMedGoogle Scholar
  75. Naukkarinen J, Rissanen A, Kaprio J, Pietiläinen KH (2012) Causes and consequences of obesity: the contribution of recent twin studies. Int J Obes (Lond) 36(8):1017–1024. doi: 10.1038/ijo.2011.192. Epub 11 Oct 2011. Review. PubMed PMID: 21986704
  76. Ng MC, Tam CH, So WY, Ho JS, Chan AW, Lee HM, Wang Y, Lam VK, Chan JC, Ma RC (2010) Implication of genetic variants near NEGR1, SEC16B, TMEM18, ETV5/DGKG, GNPDA2, LIN7C/BDNF, MTCH2, BCDIN3D/FAIM2, SH2B1, FTO, MC4R, and KCTD15 with obesity and type 2 diabetes in 7705 Chinese. J Clin Endocrinol Metab 95(5):2418–2425, PMID: 20215397PubMedGoogle Scholar
  77. Parnell JA, Reimer RA (2012) Prebiotic fiber modulation of the gut microbiota improves risk factors for obesity and the metabolic syndrome. Gut Microb 3(1):29–34, PMID: 22555633Google Scholar
  78. Peinado JR, Pardo M, de la Rosa O, Malagón MM (2012) Proteomic characterization of adipose tissue constituents, a necessary step for understanding adipose tissue complexity. Proteomics 12(4–5):607–620, PMID: 22246603PubMedGoogle Scholar
  79. Penders J, Thijs C, Mommers M, Stobberingh EE, Dompeling E, Reijmerink NE, van den Brandt PA, Kerkhof M, Koppelman GH, Postma DS (2010) Host-microbial interactions in childhood atopy: toll-like receptor 4 (TLR4), CD14, and fecal Escherichia coli. J Allergy Clin Immunol 125(1):231–236, e1–5. PMID: 20109750Google Scholar
  80. Pepino MY, Love-Gregory L, Klein S, Abumrad NA (2012) The fatty acid translocase gene CD36 and lingual lipase influence oral sensitivity to fat in obese subjects. J Lipid Res 53(3):561–566, PMID: 22210925PubMedCentralPubMedGoogle Scholar
  81. Pérez-Pérez R, López JA, García-Santos E, Camafeita E, Gómez-Serrano M, Ortega-Delgado FJ, Ricart W, Fernández-Real JM, Peral B (2012) Uncovering suitable reference proteins for expression studies in human adipose tissue with relevance to obesity. PLoS One 7(1), PMID: 22272336Google Scholar
  82. Petkeviciene J, Smalinskiene A, Luksiene DI, Jureniene K, Ramazauskiene V, Klumbiene J, Lesauskaite V (2012) Associations between apolipoprotein E genotype, diet, body mass index, and serum lipids in Lithuanian adult population. PLoS One 7(7):e41525, PMID: 22844488PubMedCentralPubMedGoogle Scholar
  83. Razquin C, Marti A, Martinez JA (2011) Evidences on three relevant obesogenes: MC4R, FTO and PPARγ. Approaches for personalized nutrition. Mol Nutr Food Res 55(1):136–149, PMID:21207518PubMedGoogle Scholar
  84. Ridlon JM, Kang DJ, Hylemon PB (2006) Bile salt biotransformations by human intestinal bacteria. J Lipid Res 47:241–259PubMedGoogle Scholar
  85. Rosskopf D, Bornhorst A, Rimmbach C, Schwahn C, Kayser A, Krüger A, Tessmann G, Geissler I, Kroemer HK, Völzke H (2007) Comment on “A common genetic variant is associated with adult and childhood obesity”. Science 315(5809):187, PMID: 17218510PubMedGoogle Scholar
  86. Roth JD, Trevaskis JL, Wilson J, Lei C, Athanacio J, Mack C, Kesty NC, Coffey T, Weyer C, Parkes DG (2008) Antiobesity effects of the beta-cell hormone amylin in combination with phentermine or sibutramine in diet-induced obese rats. Int J Obes 32(8):1201–1210, PMID: 18560368Google Scholar
  87. Rowland IR (2009) The role of the gastrointestinal microbiota in colorectal cancer. Curr Pharm Des 15(13):1524–1527PubMedGoogle Scholar
  88. Rudkowska I, Pérusse L (2012) Individualized weight management: what can be learned from nutrigenomics and nutrigenetics? Prog Mol Biol Transl Sci 108:347–382, PMID: 22656384PubMedGoogle Scholar
  89. Russell-Jones D, Gough S (2012) Recent advances in incretin-based therapies. Clin Endocrinol 77(4):489–499, PMID: 22804841Google Scholar
  90. Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, Hammer RE, Williams SC, Crowley J, Yanagisawa M, Gordon JI (2008) 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 U S A 105:16767–16772PubMedCentralPubMedGoogle Scholar
  91. Santoro N, Cirillo G, Lepore MG, Palma A, Amato A, Savarese P, Marzuillo P, Grandone A, Perrone L, Del Giudice EM (2009) Effect of the rs997509 polymorphism on the association between ectonucleotide pyrophosphatase phosphodiesterase 1 and metabolic syndrome and impaired glucose tolerance in childhood obesity. J Clin Endocrinol Metab 94(1):300–305, PMID: 18940878PubMedGoogle Scholar
  92. Sanz Y, Santacruz A, Gauffin P (2010) Gut microbiota in obesity and metabolic disorders. Proc Nutr Soc 69:434–441PubMedGoogle Scholar
  93. Schmid PM, Heid I, Buechler C, Steege A, Resch M, Birner C, Endemann DH, Riegger GA, Luchner A (2012) Expression of fourteen novel obesity-related genes in Zucker diabetic fatty rats. Cardiovasc Diabetol 11:48, PMID: 22553958PubMedCentralPubMedGoogle Scholar
  94. Schork NJ, Topol EJ (2010) Genotype-based risk and pharmacogenetic sampling in clinical trials. J Biopharm Stat 20(2):315–333PubMedCentralPubMedGoogle Scholar
  95. Serino M, Chabo C, Burcelin R (2012) Intestinal MicrobiOMICS to define health and disease in human and mice. Curr Pharm Biotechnol 13(5):746–758, PMID: 22122483PubMedGoogle Scholar
  96. Slattery ML, Lundgreen A, Welbourn B, Corcoran C, Wolff RK (2012) Genetic variation in selenoprotein genes, lifestyle, and risk of colon and rectal cancer. PLoS One 7(5):e37312, PMID: 22615972PubMedCentralPubMedGoogle Scholar
  97. Snedeker SM, Hay AG (2012) Do interactions between gut ecology and environmental chemicals contribute to obesity and diabetes? Environ Health Perspect 120(3):332–339PubMedCentralPubMedGoogle Scholar
  98. Sousa T, Paterson R, Moore V, Carlsson A, Abrahamsson B, Basit AW (2008) The gastrointestinal microbiota as a site for the biotransformation of drugs. Int J Pharm 363(1–2):1–25PubMedGoogle Scholar
  99. Spor A, Koren O, Ley R (2011) Unravelling the effects of the environment and host genotype on the gut microbiome. Nat Rev Microbiol 9:279–290PubMedGoogle Scholar
  100. Steinhardt AP, Aranguren F, Tellechea ML, Gómez Rosso LA, Brites FD, Martínez-Larrad MT, Serrano-Ríos M, Frechtel GD, Taverna MJ (2010) A functional nonsynonymous toll-like receptor 4 gene polymorphism is associated with metabolic syndrome, surrogates of insulin resistance, and syndromes of lipid accumulation. Metabolism 59(5):711–717, PMID: 19922963PubMedGoogle Scholar
  101. Stice E, Spoor S, Bohon C, Small DM (2008) Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele. Science 322(5900):449–452, PMID: 18927395PubMedGoogle Scholar
  102. Tsilidis KK, Helzlsouer KJ, Smith MW, Grinberg V, Hoffman-Bolton J, Clipp SL, Visvanathan K, Platz EA (2009) Association of common polymorphisms in IL10, and in other genes related to inflammatory response and obesity with colorectal cancer. Cancer Causes Control 20(9):1739–1751. doi: 10.1007/s10552-009-9427-7, PubMed PMID: 19760027PubMedGoogle Scholar
  103. Tiihonen K, Ouwehand AC, Rautonen N (2010) Effect of overweight on gastrointestinal microbiology and immunology: correlation with blood biomarkers. Br J Nutr 103(7):1070–1078, Epub 2009; PubMed PMID: 19930761PubMedGoogle Scholar
  104. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444:1027–1031PubMedGoogle Scholar
  105. Turnbaugh PJ, Quince C, Faith JJ, McHardy AC, Yatsunenko T, Niazi F et al (2010) Organismal, genetic, and transcriptional variation in the deeply sequenced gut microbiomes of identical twins. Proc Natl Acad Sci U S A 107(16):7503–7508PubMedCentralPubMedGoogle Scholar
  106. Velagapudi VR, Hezaveh R, Reigstad CS, Gopalacharyulu P, Yetukuri L, Islam S, Felin J, Perkins R, Borén J, Orešič M, Bäckhed F (2010) The gut microbiota modulates host energy and lipid metabolism in mice. J Lipid Res 51:1101–1112PubMedCentralPubMedGoogle Scholar
  107. Wallace TC, Guarner F, Madsen K, Cabana MD, Gibson G, Hentges E, Sanders ME (2011) Human gut microbiota and its relationship to health and disease. Nutr Rev 69(7):392–403. doi: 10.1111/j.1753-4887.2011.00402.x. Epub 30 June 2011. Review. PubMed PMID: 21729093Google Scholar
  108. Williams MJ, Almén MS, Fredriksson R, Schiöth HB (2012) What model organisms and interactomics can reveal about the genetics of human obesity. Cell Mol Life Sci 69(22):3819–3834. doi: 10.1007/s00018-012-1022-5. Epub 23 May 2012. Review. PubMed PMID: 22618246Google Scholar
  109. Winkler JK, Woehning A, Schultz JH, Brune M, Beaton N, Challa TD, Minkova S, Roeder E, Nawroth PP, Friederich HC, Wolfrum C, Rudofsky G (2012) TaqIA polymorphism in dopamine D2 receptor gene complicates weight maintenance in younger obese patients. Nutrition 28(10):996–1001, PMID: 22541053PubMedGoogle Scholar
  110. Xie B, Waters MJ, Schirra HJ (2012a) Investigating potential mechanisms of obesity by metabolomics. J Biomed Biotechnol 2012:805683, PMID: 22665992Google Scholar
  111. Xie B, Takeuchi F, Chandak GR, Kato N, Pan HW, AGEN-T2D Consortium, Zhou DH, Pan HY, Mi J (2012b) Common polymorphism near the MC4R gene is associated with type 2 diabetes: data from a meta-analysis of 123,373 individuals. Diabetologia 55(10):2660–6Google Scholar
  112. Yang RY, Havel PJ, Liu FT (2012) Galectin-12: a protein associated with lipid droplets that regulates lipid metabolism and energy balance. Adipocyte 1(2):96–100. PubMed PMID: 23700518; PubMed Central PMCID: PMC3609087Google Scholar
  113. Yoda K, He F, Miyazawa K, Kawase M, Kubota A, Hiramatsu M (2012) Orally administered heat-killed Lactobacillus gasseri TMC0356 alters respiratory immune responses and intestinal microbiota of diet-induced obese mice. J Appl Microbiol 113(1):155–162, PMID: 22519947PubMedGoogle Scholar
  114. Young EH, Wareham NJ, Farooqi S, Hinney A, Hebebrand J, Scherag A, O’rahilly S, Barroso I, Sandhu MS (2007) The V103I polymorphism of the MC4R gene and obesity: population based studies and meta-analysis of 29 563 individuals. Int J Obes (Lond) 31(9):1437–1441, PMID:17356525Google Scholar
  115. Zhang Y, Sonnenberg GE, Baye TM, Littrell J, Gunnell J, DeLaForest A, MacKinney E, Hillard CJ, Kissebah AH, Olivier M, Wilke RA (2009) Obesity-related dyslipidemia associated with FAAH, independent of insulin response, in multigenerational families of Northern European descent. Pharmacogenomics 10(12):1929–1939, PMID: 19958092PubMedCentralPubMedGoogle Scholar
  116. Zhang W, Roederer MW, Chen WQ, Fan L, Zhou HH (2012) Pharmacogenetics of drugs withdrawn from the market. Pharmacogenomics 13(2):223–231, PMID: 22256871PubMedGoogle Scholar
  117. Zuo HJ, Xie ZM, Zhang WW, Li YR, Wang W, Ding XB, Pei XF (2011) Gut bacteria alteration in obese people and its relationship with gene polymorphism. World J Gastroenterol 17(8):1076–1081, PMID: 21448362PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer India 2013

Authors and Affiliations

  • Margarita Aguilera
    • 1
    • 2
  • María Luján Jiménez-Pranteda
    • 1
  • Barbara Jenko
    • 1
    • 2
    • 3
  • Verónica Jiménez
    • 1
  • Marisa Cañadas Garre
    • 2
  1. 1.INYTA-CIBMUniversity of GranadaGranadaSpain
  2. 2.Pharmacogenetics Unit, Pharmacy ServiceUniversity Hospital Virgen de las NievesGranadaSpain
  3. 3.Institute of Biochemistry, Faculty of MedicineUniversity of LjubljanaLjubljanaSlovenia

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