The role of Gut Microbiota in the development of obesity and Diabetes

Lipids in Health and Disease

Volumn 15, Issue 1, 2016, Pages

  Baothman, Othman A ^a   Zamzami, Mazin A ^a   Taher, Ibrahim ^b   Abubaker, Jehad ^c   Abu Farha, Mohamed ^c  

^a KING ABDULAZIZ UNIVERSITY   (Saudi Arabia)

^b JOUF UNIVERSITY   (Saudi Arabia)

^c DASMAN DIABETES INSTITUTE   (Kuwait)

Author keywords

[No Author keywords available]

Indexed keywords

ACTINOBACTERIA; BACTEROIDETES; CALORIC RESTRICTION; CHEMICAL COMPOSITION; DISEASES; FIRMICUTES; GENETICS; HUMAN; ILEUM; INSULIN DEPENDENT DIABETES MELLITUS; INTESTINE FLORA; JEJUNUM; LARGE INTESTINE; LIPID DIET; MEDICINE; MICROBIAL DIVERSITY; MOUTH; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PROTEOBACTERIA; REVIEW; STOMACH; VEGETARIAN DIET; BIOSYNTHESIS; COMPLICATION; GASTROINTESTINAL TRACT; GENE EXPRESSION REGULATION; IMMUNOLOGY; INFLAMMATION; INTESTINE ABSORPTION; LIPID METABOLISM; METABOLISM; MICROBIOLOGY; PATHOLOGY; SECRETION (PROCESS); SIGNAL TRANSDUCTION;

INCRETIN; INSULIN; VOLATILE FATTY ACID;

DIABETES MELLITUS, TYPE 2; FATTY ACIDS, VOLATILE; GASTROINTESTINAL MICROBIOME; GASTROINTESTINAL TRACT; GENE EXPRESSION REGULATION; HUMANS; INCRETINS; INFLAMMATION; INSULIN; INTESTINAL ABSORPTION; LIPID METABOLISM; OBESITY; SIGNAL TRANSDUCTION;

EID: 84975799373     PISSN: None     EISSN: 1476511X     Source Type: Journal    
DOI: 10.1186/s12944-016-0278-4     Document Type: Review

References (137)

1. Ferrante D, Linetzky B, Ponce M, Goldberg L, Konfino J, Laspiur S. Prevalence of overweight, obesity, physical activity and tobacco use in Argentine youth: Global School-Based Student Health Survey and Global Youth Tobacco Survey, 2007-2012. Arch Argent Pediatr. 2014;112:496-503.
2. Rivas-Marino G, Negin J, Salinas-Rodriguez A, Manrique-Espinoza B, Sterner KN, Snodgrass J, Kowal P. Prevalence of overweight and obesity in older Mexican adults and its association with physical activity and related factors: An analysis of the study on global ageing and adult health. Am J Hum Biol. 2015;27:326-33.
3. Morgen CS, Sorensen TI. Obesity: global trends in the prevalence of overweight and obesity. Nat Rev Endocrinol. 2014;10:513-4.
4. McPherson K. Reducing the global prevalence of overweight and obesity. Lancet. 2014;384:728-30.
5. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384:766-81.
6. Quelly SB, Lieberman LS. Global prevalence of overweight and obesity in preschoolers. Anthropol Anz. 2011;68:437-56.
7. de Onis M, Blossner M, Borghi E. Global prevalence and trends of overweight and obesity among preschool children. Am J Clin Nutr. 2010;92:1257-64.
8. Jebb SA, Moore MS. Contribution of a sedentary lifestyle and inactivity to the etiology of overweight and obesity: current evidence and research issues. Med Sci Sports Exerc. 1999;31:S534-541.
9. Mayer-Davis EJ, Costacou T. Obesity and sedentary lifestyle: modifiable risk factors for prevention of type 2 diabetes. Curr Diab Rep. 2001;1:170-6.
10. Hu FB. Sedentary lifestyle and risk of obesity and type 2 diabetes. Lipids. 2003;38:103-8.
11. Cox AJ, West NP, Cripps AW. Obesity, inflammation, and the gut microbiota. Lancet Diabetes Endocrinol. 2015;3:207-15.
12. Rosenbaum M, Knight R, Leibel RL. The gut microbiota in human energy homeostasis and obesity. Trends Endocrinol Metab. 2015;26(9):493-501.
13. Tai N, Wong FS, Wen L. The role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity. Rev Endocr Metab Disord. 2015;16:55-65.
14. Villanueva-Millan MJ, Perez-Matute P, Oteo JA. Gut microbiota: a key player in health and disease. A review focused on obesity. J Physiol Biochem. 2015;71(3):509-25.
15. Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A. 2005;102:11070-5.
16. Murphy EF, Cotter PD, Healy S, Marques TM, O'Sullivan O, Fouhy F, Clarke SF, O'Toole PW, Quigley EM, Stanton C, et al. Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut. 2010;59:1635-42.
17. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027-31.
18. Cani PD, 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;3:279-88.
19. Kallus SJ, Brandt LJ. The intestinal microbiota and obesity. J Clin Gastroenterol. 2012;46:16-24.
20. Cox LM, Blaser MJ. Pathways in microbe-induced obesity. Cell Metab. 2013;17:883-94.
21. Park S, Bae JH. Probiotics for weight loss: a systematic review and meta-analysis. Nutr Res. 2015;35:566-75.
22. Prados-Bo A, Gomez-Martinez S, Nova E, Marcos A. [Role of probiotics in obesity management]. Nutr Hosp. 2015;31 Suppl 1:10-8.
23. Razmpoosh E, Javadi M, Ejtahed HS, Mirmiran P: Probiotics as beneficial agents in the management of diabetes mellitus: a systematic review. Diabetes Metab Res Rev. 2016;32(2):143-68.
24. Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, Knight R. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A. 2010;107:11971-5.
25. Tanaka S, Kobayashi T, Songjinda P, Tateyama A, Tsubouchi M, Kiyohara C, Shirakawa T, Sonomoto K, Nakayama J. Influence of antibiotic exposure in the early postnatal period on the development of intestinal microbiota. FEMS Immunol Med Microbiol. 2009;56:80-7.
26. Salminen S, Gibson GR, McCartney AL, Isolauri E. Influence of mode of delivery on gut microbiota composition in seven year old children. Gut. 2004;53:1388-9.
27. Makino H, Kushiro A, Ishikawa E, Kubota H, Gawad A, Sakai T, Oishi K, Martin R, Ben-Amor K, Knol J, Tanaka R. Mother-to-infant transmission of intestinal bifidobacterial strains has an impact on the early development of vaginally delivered infant's microbiota. PLoS One. 2013;8:e78331.
28. Munyaka PM, Khafipour E, Ghia JE. External influence of early childhood establishment of gut microbiota and subsequent health implications. Front Pediatr. 2014;2:109.
29. Tlaskalova-Hogenova H, Stepankova R, Kozakova H, Hudcovic T, Vannucci L, Tuckova L, Rossmann P, Hrncir T, Kverka M, Zakostelska Z, et al. The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases. Cell Mol Immunol. 2011;8:110-20.
30. Ji B, Nielsen J. From next-generation sequencing to systematic modeling of the gut microbiome. Front Genet. 2015;6:219.
31. Thuny F, Richet H, Casalta JP, Angelakis E, Habib G, Raoult D. Vancomycin treatment of infective endocarditis is linked with recently acquired obesity. PLoS One. 2010;5:e9074.
32. Saari A, Virta LJ, Sankilampi U, Dunkel L, Saxen H. Antibiotic exposure in infancy and risk of being overweight in the first 24 months of life. Pediatrics. 2015;135:617-26.
33. Keeney KM, Yurist-Doutsch S, Arrieta MC, Finlay BB. Effects of antibiotics on human microbiota and subsequent disease. Annu Rev Microbiol. 2014;68:217-35.
34. Panda S, El khader I, Casellas F, Lopez Vivancos J, Garcia Cors M, Santiago A, Cuenca S, Guarner F, Manichanh C. Short-term effect of antibiotics on human gut microbiota. PLoS One. 2014;9:e95476.
35. Zhang Y, Limaye PB, Renaud HJ, Klaassen CD. Effect of various antibiotics on modulation of intestinal microbiota and bile acid profile in mice. Toxicol Appl Pharmacol. 2014;277:138-45.
36. Szych J, Wolkowicz T, La Ragione R, Madajczak G. Impact of antibiotics on the intestinal microbiota and on the treatment of Shiga-toxin-producing Escherichia coli and Salmonella infections. Curr Pharm Des. 2014;20:4535-48.
37. Angelakis E, Merhej V, Raoult D. Related actions of probiotics and antibiotics on gut microbiota and weight modification. Lancet Infect Dis. 2013;13:889-99.
38. Aguilera M, Vergara P, Martinez V. Stress and antibiotics alter luminal and wall-adhered microbiota and enhance the local expression of visceral sensory-related systems in mice. Neurogastroenterol Motil. 2013;25:e515-529.
39. Tian B, Fadhil NH, Powell JE, Kwong WK, Moran NA: Long-term exposure to antibiotics has caused accumulation of resistance determinants in the gut microbiota of honeybees. MBio. 2012;3(6):e00377-12.
40. Ray K. Gut microbiota: adding weight to the microbiota's role in obesity - exposure to antibiotics early in life can lead to increased adiposity. Nat Rev Endocrinol. 2012;8:623.
41. Ubeda C, Pamer EG. Antibiotics, microbiota, and immune defense. Trends Immunol. 2012;33:459-66.
42. Quigley EM. Therapies aimed at the gut microbiota and inflammation: antibiotics, prebiotics, probiotics, synbiotics, anti-inflammatory therapies. Gastroenterol Clin North Am. 2011;40:207-22.
43. Iapichino G, Callegari ML, Marzorati S, Cigada M, Corbella D, Ferrari S, Morelli L. Impact of antibiotics on the gut microbiota of critically ill patients. J Med Microbiol. 2008;57:1007-14.
44. Modi SR, Collins JJ, Relman DA. Antibiotics and the gut microbiota. J Clin Invest. 2014;124:4212-8.
45. Jakobsson HE, Jernberg C, Andersson AF, Sjolund-Karlsson M, Jansson JK, Engstrand L. Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. PLoS One. 2010;5:e9836.
46. Maukonen J, Saarela M. Human gut microbiota: does diet matter? Proc Nutr Soc. 2015;74:23-36.
47. Wu GD, Bushmanc FD, Lewis JD. Diet, the human gut microbiota, and IBD. Anaerobe. 2013;24:117-20.
48. Rothe M, Blaut M. Evolution of the gut microbiota and the influence of diet. Benef Microbes. 2013;4:31-7.
49. Scott KP, Gratz SW, Sheridan PO, Flint HJ, Duncan SH. The influence of diet on the gut microbiota. Pharmacol Res. 2013;69:52-60.
50. Moreira AP, Texeira TF, Ferreira AB, Peluzio Mdo C, Alfenas Rde C. Influence of a high-fat diet on gut microbiota, intestinal permeability and metabolic endotoxaemia. Br J Nutr. 2012;108:801-9.
51. Clarke SF, Murphy EF, Nilaweera K, Ross PR, Shanahan F, O'Toole PW, Cotter PD. The gut microbiota and its relationship to diet and obesity: new insights. Gut Microbes. 2012;3:186-202.
52. Wong JM, Esfahani A, Singh N, Villa CR, Mirrahimi A, Jenkins DJ, Kendall CW. Gut microbiota, diet, and heart disease. J AOAC Int. 2012;95:24-30.
53. Brown K, DeCoffe D, Molcan E, Gibson DL. Diet-induced dysbiosis of the intestinal microbiota and the effects on immunity and disease. Nutrients. 2012;4:1095-119.
54. Pozo-Rubio T, Mujico JR, Marcos A, Puertollano E, Nadal I, Sanz Y, Nova E. Immunostimulatory effect of faecal Bifidobacterium species of breast-fed and formula-fed infants in a peripheral blood mononuclear cell/Caco-2 co-culture system. Br J Nutr. 2011;106:1216-23.
55. Roger LC, Costabile A, Holland DT, Hoyles L, McCartney AL. Examination of faecal Bifidobacterium populations in breast- and formula-fed infants during the first 18 months of life. Microbiology. 2010;156:3329-41.
56. Chen J, Cai W, Feng Y. Development of intestinal bifidobacteria and lactobacilli in breast-fed neonates. Clin Nutr. 2007;26:559-66.
57. Rubaltelli FF, Biadaioli R, Pecile P, Nicoletti P. Intestinal flora in breast- and bottle-fed infants. J Perinat Med. 1998;26:186-91.
58. Benno Y, Sawada K, Mitsuoka T. The intestinal microflora of infants: composition of fecal flora in breast-fed and bottle-fed infants. Microbiol Immunol. 1984;28:975-86.
59. Yoshioka H, Iseki K, Fujita K. Development and differences of intestinal flora in the neonatal period in breast-fed and bottle-fed infants. Pediatrics. 1983;72:317-21.
60. Jones ML, Martoni CJ, Prakash S. Cholesterol lowering and inhibition of sterol absorption by Lactobacillus reuteri NCIMB 30242: a randomized controlled trial. Eur J Clin Nutr. 2012;66:1234-41.
61. Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr. 1995;125:1401-12.
62. Gibson GR, Probert HM, Loo JV, Rastall RA, Roberfroid MB. Dietary modulation of the human colonic microbiota: updating the concept of prebiotics. Nutr Res Rev. 2004;17:259-75.
63. Macfarlane GT, Steed H, Macfarlane S. Bacterial metabolism and health-related effects of galacto-oligosaccharides and other prebiotics. J Appl Microbiol. 2008;104:305-44.
64. De los Reyes-Gavilan CG, Delzenne NM, Gonzalez S, Gueimonde M, Salazar N. Development of functional foods to fight against obesity Opportunities for probiotics and prebiotics. Agro Food Ind Hi Tech. 2014;25:35-9.
65. Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med. 2009;1:6ra14.
66. Bruce-Keller AJ, Salbaum JM, Luo M, Blanchard E, Taylor CM, Welsh DA, Berthoud HR. Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity. Biol Psychiatry. 2015;77:607-15.
67. Tsai YT, Cheng PC, Pan TM. Anti-obesity effects of gut microbiota are associated with lactic acid bacteria. Appl Microbiol Biotechnol. 2014;98:1-10.
68. Boroni Moreira AP, Fiche Salles Teixeira T, do C Gouveia Peluzio M, de Cassia Goncalves Alfenas R. Gut microbiota and the development of obesity. Nutr Hosp. 2012;27:1408-14.
69. Tagliabue A, Elli M. The role of gut microbiota in human obesity: recent findings and future perspectives. Nutr Metab Cardiovasc Dis. 2013;23:160-8.
70. Murphy EF, Cotter PD, Hogan A, O'Sullivan O, Joyce A, Fouhy F, Clarke SF, Marques TM, O'Toole PW, Stanton C, et al. Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity. Gut. 2013;62:220-6.
71. Flint HJ. Obesity and the gut microbiota. J Clin Gastroenterol. 2011;45(Suppl):S128-132.
72. Delzenne NM, Neyrinck AM, Backhed F, Cani PD. Targeting gut microbiota in obesity: effects of prebiotics and probiotics. Nat Rev Endocrinol. 2011;7:639-46.
73. Scarpellini E, Campanale M, Leone D, Purchiaroni F, Vitale G, Lauritano EC, Gasbarrini A. Gut microbiota and obesity. Intern Emerg Med. 2010;5 Suppl 1:S53-56.
74. Musso G, Gambino R, Cassader M. Obesity, diabetes, and gut microbiota: the hygiene hypothesis expanded? Diabetes Care. 2010;33:2277-84.
75. Cani PD, Delzenne NM. Involvement of the gut microbiota in the development of low grade inflammation associated with obesity: focus on this neglected partner. Acta Gastroenterol Belg. 2010;73:267-9.
76. Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, Parameswaran P, Crowell MD, Wing R, Rittmann BE, Krajmalnik-Brown R. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci U S A. 2009;106:2365-70.
77. Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008;57:1470-81.
78. Tremaroli V, Karlsson F, Werling M, Stahlman M, Kovatcheva-Datchary P, Olbers T, Fandriks L, le Roux CW, Nielsen J, Backhed F. Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation. Cell Metab. 2015;22:228-38.
79. Lutz TA, Bueter M. Physiological mechanisms behind Roux-en-Y gastric bypass surgery. Dig Surg. 2014;31:13-24.
80. Osto M, Abegg K, Bueter M, le Roux CW, Cani PD, Lutz TA. Roux-en-Y gastric bypass surgery in rats alters gut microbiota profile along the intestine. Physiol Behav. 2013;119:92-6.
81. Kugelberg E. Surgery: Altered gut microbiota trigger weight loss. Nat Rev Endocrinol. 2013;9:314.
82. Kong LC, Tap J, Aron-Wisnewsky J, Pelloux V, Basdevant A, Bouillot JL, Zucker JD, Dore J, Clement K. Gut microbiota after gastric bypass in human obesity: increased richness and associations of bacterial genera with adipose tissue genes. Am J Clin Nutr. 2013;98:16-24.
83. Graessler J, Qin Y, Zhong H, Zhang J, Licinio J, Wong ML, Xu A, Chavakis T, Bornstein AB, Ehrhart-Bornstein M, et al. Metagenomic sequencing of the human gut microbiome before and after bariatric surgery in obese patients with type 2 diabetes: correlation with inflammatory and metabolic parameters. Pharmacogenomics J. 2013;13:514-22.
84. Bueter M, Abegg K, Seyfried F, Lutz TA, le Roux CW: Roux-en-Y gastric bypass operation in rats. J Vis Exp 2012:e3940.
85. Aron-Wisnewsky J, Dore J, Clement K. The importance of the gut microbiota after bariatric surgery. Nat Rev Gastroenterol Hepatol. 2012;9:590-8.
86. Woodard GA, Encarnacion B, Downey JR, Peraza J, Chong K, Hernandez-Boussard T, Morton JM. Probiotics improve outcomes after Roux-en-Y gastric bypass surgery: a prospective randomized trial. J Gastrointest Surg. 2009;13:1198-204.
87. Liou AP, Paziuk M, Luevano Jr JM, Machineni S, Turnbaugh PJ, Kaplan LM. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med. 2013;5:178ra141.
88. Gao Z, Yin J, Zhang J, Ward RE, Martin RJ, Lefevre M, Cefalu WT, Ye J. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes. 2009;58:1509-17.
89. Lin HV, Frassetto A, Kowalik Jr EJ, Nawrocki AR, Lu MM, Kosinski JR, Hubert JA, Szeto D, Yao X, Forrest G, Marsh DJ. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One. 2012;7:e35240.
90. Yamashita H, Fujisawa K, Ito E, Idei S, Kawaguchi N, Kimoto M, Hiemori M, Tsuji H. Improvement of obesity and glucose tolerance by acetate in Type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Biosci Biotechnol Biochem. 2007;71:1236-43.
91. Fernandes J, Su W, Rahat-Rozenbloom S, Wolever TM, Comelli EM. Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans. Nutr Diabetes. 2014;4:e121.
92. Schwiertz A, Taras D, Schafer K, Beijer S, Bos NA, Donus C, Hardt PD. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring). 2010;18:190-5.
93. den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res. 2013;54(9):2325-40.
94. Nohr MK, Pedersen MH, Gille A, Egerod KL, Engelstoft MS, Husted AS, Sichlau RM, Grunddal KV, Poulsen SS, Han S, et al. GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids in enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric leukocytes. Endocrinology. 2013;154:3552-64.
95. Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, Cameron J, Grosse J, Reimann F, Gribble FM. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2012;61:364-71.
96. Kasubuchi M, Hasegawa S, Hiramatsu T, Ichimura A, Kimura I. Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients. 2015;7:2839-49.
97. Kimura I, Inoue D, Hirano K, Tsujimoto G. The SCFA receptor GPR43 and energy metabolism. Front Endocrinol (Lausanne). 2014;5:85.
98. Bjursell M, Admyre T, Goransson M, Marley AE, Smith DM, Oscarsson J, Bohlooly YM. Improved glucose control and reduced body fat mass in free fatty acid receptor 2-deficient mice fed a high-fat diet. Am J Physiol Endocrinol Metab. 2011;300:E211-220.
99. Kimura I, Ozawa K, Inoue D, Imamura T, Kimura K, Maeda T, Terasawa K, Kashihara D, Hirano K, Tani T, et al. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat Commun. 2013;4:1829.
100. Chambers ES, Morrison DJ, Frost G. Control of appetite and energy intake by SCFA: what are the potential underlying mechanisms? Proc Nutr Soc. 2015;74:328-36.
101. Kaji I, Karaki S, Kuwahara A. Short-chain fatty acid receptor and its contribution to glucagon-like peptide-1 release. Digestion. 2014;89:31-6.
102. Conterno L, Fava F, Viola R, Tuohy KM. Obesity and the gut microbiota: does up-regulating colonic fermentation protect against obesity and metabolic disease? Genes Nutr. 2011;6:241-60.
103. Ye D, Li FY, Lam KS, Li H, Jia W, Wang Y, Man K, Lo CM, Li X, Xu A. Toll-like receptor-4 mediates obesity-induced non-alcoholic steatohepatitis through activation of X-box binding protein-1 in mice. Gut. 2012;61:1058-67.
104. Kim SJ, Choi Y, Choi YH, Park T. Obesity activates toll-like receptor-mediated proinflammatory signaling cascades in the adipose tissue of mice. J Nutr Biochem. 2012;23:113-22.
105. Karagiannides I, Pothoulakis C. Obesity, innate immunity and gut inflammation. Curr Opin Gastroenterol. 2007;23:661-6.
106. Creely SJ, McTernan PG, Kusminski CM, Fisher f M, Da Silva NF, Khanolkar M, Evans M, Harte AL, 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:E740-747.
107. Rodes L, Khan A, Paul A, Coussa-Charley M, Marinescu D, Tomaro-Duchesneau C, Shao W, Kahouli I, Prakash S. Effect of probiotics Lactobacillus and Bifidobacterium on gut-derived lipopolysaccharides and inflammatory cytokines: an in vitro study using a human colonic microbiota model. J Microbiol Biotechnol. 2013;23:518-26.
108. Gulden E, Wong FS, Wen L. The gut microbiota and Type 1 Diabetes. Clin Immunol. 2015;159(2):143-53.
109. Murri M, Leiva I, Gomez-Zumaquero JM, Tinahones FJ, Cardona F, Soriguer F, Queipo-Ortuno MI. Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study. BMC Med. 2013;11:46.
110. Brown CT, Davis-Richardson AG, Giongo A, Gano KA, Crabb DB, Mukherjee N, Casella G, Drew JC, Ilonen J, Knip M, et al. Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes. PLoS One. 2011;6:e25792.
111. Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC, Hu C, Wong FS, Szot GL, Bluestone JA, et al. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature. 2008;455:1109-13.
112. Lucas K, Maes M. Role of the Toll Like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway. Mol Neurobiol. 2013;48:190-204.
113. Atkinson MA, Chervonsky A. Does the gut microbiota have a role in type 1 diabetes? Early evidence from humans and animal models of the disease. Diabetologia. 2012;55:2868-77.
114. Burrows MP, Volchkov P, Kobayashi KS, Chervonsky AV. Microbiota regulates type 1 diabetes through Toll-like receptors. Proc Natl Acad Sci U S A. 2015;112:9973-7.
115. Hara N, Alkanani AK, Ir D, Robertson CE, Wagner BD, Frank DN, Zipris D. The role of the intestinal microbiota in type 1 diabetes. Clin Immunol. 2013;146:112-9.
116. King C, Sarvetnick N. The incidence of type-1 diabetes in NOD mice is modulated by restricted flora not germ-free conditions. PLoS One. 2011;6:e17049.
117. Marietta EV, Gomez AM, Yeoman C, Tilahun AY, Clark CR, Luckey DH, Murray JA, White BA, Kudva YC, Rajagopalan G. Low incidence of spontaneous type 1 diabetes in non-obese diabetic mice raised on gluten-free diets is associated with changes in the intestinal microbiome. PLoS One. 2013;8:e78687.
118. Mathis D, Benoist C. The influence of the microbiota on type-1 diabetes: on the threshold of a leap forward in our understanding. Immunol Rev. 2012;245:239-49.
119. Vaarala O. The gut as a regulator of early inflammation in type 1 diabetes. Curr Opin Endocrinol Diabetes Obes. 2011;18:241-7.
120. Vaarala O. Human intestinal microbiota and type 1 diabetes. Curr Diab Rep. 2013;13:601-7.
121. Vaarala O, Atkinson MA, Neu J. The "perfect storm" for type 1 diabetes: the complex interplay between intestinal microbiota, gut permeability, and mucosal immunity. Diabetes. 2008;57:2555-62.
122. Yang C, Fei Y, Qin Y, Luo D, Yang S, Kou X, Zi Y, Deng T, Jin M. Bacterial Flora Changes in Conjunctiva of Rats with Streptozotocin-Induced Type I Diabetes. PLoS One. 2015;10:e0133021.
123. Cani PD, Delzenne NM. The role of the gut microbiota in energy metabolism and metabolic disease. Curr Pharm Des. 2009;15:1546-58.
124. Cani PD, Possemiers S, Van de Wiele T, Guiot Y, Everard A, Rottier O, Geurts L, Naslain D, Neyrinck A, Lambert DM, 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.
125. Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, Liang S, Zhang W, Guan Y, Shen D, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012;490:55-60.
126. Amyot J, Semache M, Ferdaoussi M, Fontes G, Poitout V. Lipopolysaccharides impair insulin gene expression in isolated islets of Langerhans via Toll-Like Receptor-4 and NF-kappaB signalling. PLoS One. 2012;7:e36200.
127. Caricilli AM, Picardi PK, de Abreu LL, Ueno M, Prada PO, Ropelle ER, Hirabara SM, Castoldi A, Vieira P, Camara NO, et al. Gut microbiota is a key modulator of insulin resistance in TLR 2 knockout mice. PLoS Biol. 2011;9:e1001212.
128. Dali-Youcef N, Mecili M, Ricci R, Andres E. Metabolic inflammation: connecting obesity and insulin resistance. Ann Med. 2013;45:242-53.
129. Tanti JF, Ceppo F, Jager J, Berthou F. Implication of inflammatory signaling pathways in obesity-induced insulin resistance. Front Endocrinol (Lausanne). 2012;3:181.
130. Hamilton MK, Boudry G, Lemay DG, Raybould HE. Changes in intestinal barrier function and gut microbiota in high-fat diet-fed rats are dynamic and region dependent. Am J Physiol Gastrointest Liver Physiol. 2015;308:G840-851.
131. Kim KA, Gu W, Lee IA, Joh EH, Kim DH. High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PLoS One. 2012;7:e47713.
132. Chen D, Yang Z, Chen X, Huang Y, Yin B, Guo F, Zhao H, Huang J, Wu Y, Gu R. Effect of Lactobacillus rhamnosus hsryfm 1301 on the Gut Microbiota and Lipid Metabolism in Rats Fed a High-Fat Diet. J Microbiol Biotechnol. 2015;25:687-95.
133. de La Serre CB, Ellis CL, Lee J, Hartman AL, Rutledge JC, Raybould HE. 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:G440-448.
134. Zimmer J, Lange B, Frick JS, Sauer H, Zimmermann K, Schwiertz A, Rusch K, Klosterhalfen S, Enck P. A vegan or vegetarian diet substantially alters the human colonic faecal microbiota. Eur J Clin Nutr. 2012;66:53-60.
135. Kim MS, Hwang SS, Park EJ, Bae JW. Strict vegetarian diet improves the risk factors associated with metabolic diseases by modulating gut microbiota and reducing intestinal inflammation. Environ Microbiol Rep. 2013;5:765-75.
136. De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, Collini S, Pieraccini G, Lionetti P. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A. 2010;107:14691-6.
137. Zhang C, Li S, Yang L, Huang P, Li W, Wang S, Zhao G, Zhang M, Pang X, Yan Z, et al. Structural modulation of gut microbiota in life-long calorie-restricted mice. Nat Commun. 2013;4:2163.