Effect of antibiotics on gut microbiota, glucose metabolism and body weight regulation: A review of the literature

Diabetes, Obesity and Metabolism

Volumn 18, Issue 5, 2016, Pages 444-453

  Mikkelsen, K H ^a,b   Allin, K H ^b   Knop, F K ^a,b  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b Capital Region   (Denmark)

Author keywords

Glucose metabolism; Observational study; Pharmaco epidemiology; Type 2 diabetes

Indexed keywords

AMOXICILLIN; ANTIBIOTIC AGENT; BILE ACID; CLARITHROMYCIN; GENTAMICIN; MEROPENEM; PENICILLIN DERIVATIVE; PLACEBO; SHORT CHAIN FATTY ACID; TETRACYCLINE; VANCOMYCIN; ANTIINFECTIVE AGENT;

AMEBIASIS; BACTERIAL LOAD; CYSTIC FIBROSIS; DIARRHEA; DISEASE ASSOCIATION; DRUG EFFICACY; DRUG EXPOSURE; DRUG SAFETY; GLUCOSE METABOLISM; HELICOBACTER INFECTION; HUMAN; INFECTION; INFLAMMATION; INTESTINE FLORA; META ANALYSIS (TOPIC); METABOLIC SYNDROME X; MICROBIAL COLONIZATION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; ORAL GLUCOSE TOLERANCE TEST; PHARMACODYNAMICS; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK BENEFIT ANALYSIS; SIDE EFFECT; WEIGHT CONTROL; WEIGHT GAIN; ANIMAL; BIOLOGICAL MODEL; BODY WEIGHT; CHEMICALLY INDUCED; DIABETES MELLITUS, TYPE 2; DRUG EFFECTS; DYSBIOSIS; ENERGY METABOLISM; FOOD INTAKE; INSULIN RESISTANCE; MICROBIOLOGY; OBSERVATIONAL STUDY; OVERWEIGHT; PATHOPHYSIOLOGY;

ANIMALS; ANTI-BACTERIAL AGENTS; APPETITE REGULATION; BODY WEIGHT; DIABETES MELLITUS, TYPE 2; DYSBIOSIS; ENERGY METABOLISM; GASTROINTESTINAL MICROBIOME; HUMANS; INSULIN RESISTANCE; MODELS, BIOLOGICAL; OBSERVATIONAL STUDIES AS TOPIC; OVERWEIGHT;

EID: 84959512389     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/dom.12637     Document Type: Review

References (111)

1. Xu J, Gordon JI. Honor thy symbionts. Proc Natl Acad Sci U S A 2003; 100: 10452-10459.
2. Qin J, Li Y, Cai Z etal. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 2012; 490: 55-60.
3. Karlsson FH, Tremaroli V, Nookaew I etal. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 2013; 498: 99-103.
4. Le Chatelier E, Nielsen T, Qin J etal. Richness of human gut microbiome correlates with metabolic markers. Nature 2013; 500: 541-546.
5. 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: 1027-1031.
6. Bäckhed F, Ding H, Wang T etal. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A 2004; 101: 15718-15723.
7. Vrieze A, Van Nood E, Holleman F etal. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology; 143: 913-916.e7.
8. Ridaura VK, Faith JJ, Rey FE etal. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 2013; 341: 1241214.
9. Martin G. p-Aminobenzoic Acid and sulfonamides in rat nutrition. Exp Biol Med 1942; 51: 56-59.
10. Dibner JJ, Richards JD. Antibiotic growth promoters in agriculture: history and mode of action. Poult Sci 2005; 84: 634-643.
11. Saiman L, Anstead M, Mayer-Hamblett N etal. Effect of azithromycin on pulmonary function in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA 2010; 303: 1707-1715.
12. Gough EK, Moodie EEM, Prendergast AJ etal. The impact of antibiotics on growth in children in low and middle income countries: systematic review and meta-analysis of randomised controlled trials. BMJ 2014; 348: g2267.
13. Mueller NT, Whyatt R, Hoepner L etal. Prenatal exposure to antibiotics, cesarean section and risk of childhood obesity. Int J Obes (Lond) 2015; 39: 665-670.
14. Mor A, Antonsen S, Kahlert J etal. Prenatal exposure to systemic antibacterials and overweight and obesity in Danish schoolchildren: a prevalence study. Int J Obes (Lond) 2015; 39: 1450-1455.
15. Cocoros NM, Lash TL, Nørgaard M, Farkas DK, DeMaria A, Sørensen HT. Hospitalized prenatal and childhood infections and obesity in Danish male conscripts. Ann Epidemiol 2013; 23: 307-313.
16. Trasande L, Blustein J, Liu M, Corwin E, Cox LM, Blaser MJ. Infant antibiotic exposures and early-life body mass. Int J Obes (Lond) 2013; 37: 16-23.
17. Ajslev TA, Andersen CS, Gamborg M, Sørensen TIA, Jess T. Childhood overweight after establishment of the gut microbiota: the role of delivery mode, pre-pregnancy weight and early administration of antibiotics. Int J Obes (Lond) 2011; 35: 522-529.
18. Bailey LC, Forrest CB, Zhang P, Richards TM, Livshits A, DeRusso PA. Association of antibiotics in infancy with early childhood obesity. JAMA Pediatr 2014; 168: 1063-1069.
19. Murphy R, Stewart AW, Braithwaite I, Beasley R, Hancox RJ, Mitchell EA. Antibiotic treatment during infancy and increased body mass index in boys: an international cross-sectional study. Int J Obes (Lond) 2014; 38: 1115-1119.
20. Azad MB, Bridgman SL, Becker AB, Kozyrskyj AL. Infant antibiotic exposure and the development of childhood overweight and central adiposity. Int J Obes (Lond) 2014; 38: 1290-1298.
21. 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: 617-626.
22. Burgner D, Sabin M, Magnussen C etal. Infection-related hospitalization in childhood and adult metabolic outcomes. Pediatrics 2015; 136: 554-562.
23. Yamada T, Hara K, Kadowaki T. Association of adenovirus 36 infection with obesity and metabolic markers in humans: a meta-analysis of observational studies. PLoS One 2012; 7: e42031.
24. Lassenius MI, Pietilainen KH, Kaartinen K etal. Bacterial endotoxin activity in human serum is associated with dyslipidemia, insulin resistance, obesity, and chronic inflammation. Diabetes Care 2011; 34: 1809-1815.
25. Blustein J, Attina T, Liu M etal. Association of caesarean delivery with child adiposity from age 6 weeks to 15 years. Int J Obes (Lond) 2013; 37: 900-906.
26. Thuny F, Richet H, Casalta J-P, Angelakis E, Habib G, Raoult D. Vancomycin treatment of infective endocarditis is linked with recently acquired obesity. PLoS One 2010; 5: e9074.
27. Angelakis E, Million M, Kankoe S etal. Abnormal weight gain and gut microbiota modifications are side effects of long-term doxycycline and hydroxychloroquine treatment. Antimicrob Agents Chemother 2014; 58: 3342-3347.
28. Francois F, Roper J, Joseph N etal. The effect of H pylori eradication on meal-associated changes in plasma ghrelin and leptin. BMC Gastroenterol 2011; 11: 37.
29. Lane JA, Murray LJ, Harvey IM, Donovan JL, Nair P, Harvey RF. Randomised clinical trial: helicobacter pylori eradication is associated with a significantly increased body mass index in a placebo-controlled study. Aliment Pharmacol Ther 2011; 33: 922-929.
30. Haight TH, Pierce WE. Effect of prolonged antibiotic administration on the weight of healthy young males one figure. J Nutr 1955; 56: 151-161.
31. Mikkelsen KH, Frost M, Bahl MI etal. Effect of antibiotics on gut microbiota, gut hormones and glucose metabolism. PLoS One 2015; 10: e0142352.
32. Chou H-W, Wang J-L, Chang C-H, Lee J-J, Shau W-Y, Lai M-S. Risk of severe dysglycemia among diabetic patients receiving levofloxacin, ciprofloxacin, or moxifloxacin in Taiwan. Clin Infect Dis 2013; 57: 971-980.
33. Mohr JF, McKinnon PS, Peymann PJ, Kenton I, Septimus E, Okhuysen PC. A retrospective, comparative evaluation of dysglycemias in hospitalized patients receiving gatifloxacin, levofloxacin, ciprofloxacin, or ceftriaxone. Pharmacother J Hum Pharmacol Drug Ther 2005; 25: 1303-1309.
34. Boursi B, Mamtani R, Haynes K, Yang Y-X. The effect of past antibiotic exposure on diabetes risk. Eur J Endocrinol 2015; 172: 639-648.
35. Mikkelsen KH, Knop FK, Frost M, Hallas J, Pottegård A. Use of antibiotics and risk of type 2 diabetes: a population-based case-control study. J Clin Endocrinol Metab 2015; 100: 3633-3640.
36. Falagas ME, Kompoti M. Obesity and infection. Lancet Infect Dis 2006; 6: 438-446.
37. Vrieze A, Out C, Fuentes S etal. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity. J Hepatol 2014; 60: 824-831.
38. Reijnders D, Goosens G, Neis E etal. Effects of gut microbiota manipulation by antibiotics on host metabolism in obese humans. Conference Abstract, EMBL, Heidelberg, 2015.
39. Di Caprio JM, Rantz LA. Effects of terramycin on the bacterial flora of the bowel in man. AMA Arch Intern Med 1950; 86: 649-657.
40. Nord CE. The effect of antimicrobial agents on the ecology of the human intestinal microflora. Vet Microbiol 1993; 35: 193-197.
41. Rettedal EA, Gumpert H, Sommer MOA. Cultivation-based multiplex phenotyping of human gut microbiota allows targeted recovery of previously uncultured bacteria. Nat Commun 2014; 5: 4714.
42. Kuczynski J, Lauber CL, Walters WA etal. Experimental and analytical tools for studying the human microbiome. Nat Rev Genet 2011; 13: 47-58.
43. Jernberg C, Löfmark S, Edlund C, Jansson JK. Long-term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J 2007; 1: 56-66.
44. Jakobsson HE, Jernberg C, Andersson AF, Sjölund-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.
45. Dethlefsen L, Relman DA. Colloquium paper: incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci U S A 2010; 108: 4554-4561.
46. Panda S, El khader I, Casellas F etal. Short-term effect of antibiotics on human gut microbiota. PLoS One 2014; 9: e95476.
47. Pallav K, Dowd SE, Villafuerte J etal. Effects of polysaccharopeptide from Trametes versicolor and amoxicillin on the gut microbiome of healthy volunteers: a randomized clinical trial. Gut Microbes 2014; 5: 458-467.
48. Zaura E, Brandt BW, Teixeira de Mattos MJ etal. Same exposure but two radically different responses to antibiotics: resilience of the salivary microbiome versus long-term microbial shifts in feces. mBIO 2015; 6: e01693-15.
49. Cochetière MFDL, Durand T, Lepage P, Bourreille A, Galmiche JP, Doré J. Resilience of the dominant human fecal microbiota upon short-course antibiotic challenge. J Clin Microbiol 2005; 43: 5588-5592.
50. Fouhy F, Guinane CM, Hussey S etal. High-throughput sequencing reveals the incomplete, short-term recovery of infant gut microbiota following parenteral antibiotic treatment with ampicillin and gentamicin. Antimicrob Agents Chemother 2012; 56: 5811-5820.
51. Arat S, Spivak A, Horn SV etal. Microbiome changes in healthy volunteers treated with GSK1322322, a novel antibiotic targeting bacterial peptide deformylase. Antimicrob Agents Chemother 2015; 59: 1182-1192.
52. Arboleya S, Sánchez B, Milani C etal. Intestinal microbiota development in preterm neonates and effect of perinatal antibiotics. J Pediatr 2015; 166: 538-544.
53. Clarke SF, Murphy EF, O'Sullivan O etal. Exercise and associated dietary extremes impact on gut microbial diversity. Gut 2014; 63: 1913-1920.
54. Forslund K, Hildebrand F, Nielsen T etal. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 2015; 528: 262-266.
55. Wu GD, Chen J, Hoffmann C etal. Linking long-term dietary patterns with gut microbial enterotypes. Science 2011; 334: 105-108.
56. Bajaj JS, Heuman DM, Sanyal AJ etal. Modulation of the metabiome by rifaximin in patients with cirrhosis and minimal hepatic encephalopathy. PLoS One 2013; 8: 60042.
57. Raymond F, Ouameur AA, Déraspe M etal. The initial state of the human gut microbiome determines its reshaping by antibiotics. ISME J 2015; doi: 10.1038/ismej.2015.148. [Epub ahead of print].
58. Cho I, Yamanishi S, Cox L etal. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature 2012; 488: 621-626.
59. Chevalier C, Stojanović O, Colin DJ etal. Gut microbiota orchestrates energy homeostasis during cold. Cell 2015; 163: 1360-1374.
60. Gill SR, Pop M, DeBoy RT etal. Metagenomic analysis of the human distal gut microbiome. Science 2006; 312: 1355-1359.
61. Cummings JH, Pomare EW, Branch WJ, Naylor CP, Macfarlane GT. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 1987; 28: 1221-1227.
62. Macfarlane G, Gibson G. Carbohydrate fermentation, energy transduction and gas metabolism in the human large intestine. In: Mackie RI, White BA, eds. Gastrointestinal Microbiology, Vol. 1. London: Chapman and Hall, 1997; 269-318.
63. Crawford PA, Crowley JR, Sambandam N etal. Regulation of myocardial ketone body metabolism by the gut microbiota during nutrient deprivation. Proc Natl Acad Sci U S A 2009; 106: 11276-11281.
64. Lin HV, Frassetto A, Kowalik EJ Jr etal. 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.
65. Tolhurst G, Heffron H, Lam YS etal. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 2011; 61: 364-371.
66. Duca FA, Lam TKT. Gut microbiota, nutrient sensing and energy balance. Diabetes Obes Metab 2014; 16: 68-76.
67. Samuel BS, Shaito A, Motoike T etal. 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 2008; 105: 16767-16772.
68. Cani PD, Possemiers S, Van de Wiele T etal. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 2009; 58: 1091-1103.
69. Duca FA, Swartz TD, Sakar Y, Covasa M. Increased oral detection, but decreased intestinal signaling for fats in mice lacking gut microbiota. PLoS One 2012; 7: e39748.
70. Cherbut C, Ferrier L, Rozé C etal. Short-chain fatty acids modify colonic motility through nerves and polypeptide YY release in the rat. Am J Physiol Gastrointest Liver Physiol 1998; 275: G1415-G1422.
71. Wichmann A, Allahyar A, Greiner TU etal. Microbial modulation of energy availability in the colon regulates intestinal transit. Cell Host Microbe 2013; 14: 582-590.
72. Carvalho BM, Guadagnini D, Tsukumo DML etal. Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice. Diabetologia 2012; 55: 2823-2834.
73. Garner CD, Antonopoulos DA, Wagner B etal. Perturbation of the small intestine microbial ecology by streptomycin alters pathology in a salmonella enterica serovar typhimurium murine model of infection. Infect Immun 2009; 77: 2691-2702.
74. Roberfroid MB. Prebiotics and synbiotics: concepts and nutritional properties. Br J Nutr 1998; 80: S197-S202.
75. Nilsson A, Johansson E, Ekström L, Björck I. Effects of a brown beans evening meal on metabolic risk markers and appetite regulating hormones at a subsequent standardized breakfast: a randomized cross-over study. PLoS One 2013; 8: e59985.
76. Parnell JA, Reimer RA. Prebiotic fibres dose-dependently increase satiety hormones and alter Bacteroidetes and Firmicutes in lean and obese JCR:LA-cp rats. Br J Nutr 2012; 107: 601-613.
77. Russo F, Linsalata M, Clemente C etal. Inulin-enriched pasta improves intestinal permeability and modifies the circulating levels of zonulin and glucagon-like peptide 2 in healthy young volunteers. Nutr Res 2012; 32: 940-946.
78. Kellow NJ, Coughlan MT, Reid CM. Metabolic benefits of dietary prebiotics in human subjects: a systematic review of randomised controlled trials. Br J Nutr 2014; 111: 1147-1161.
79. Høverstad T, Carlstedt-Duke B, Lingaas E etal. Influence of ampicillin, clindamycin, and metronidazole on faecal excretion of short-chain fatty acids in healthy subjects. Scand J Gastroenterol 1986; 21: 621-626.
80. Lewis S, Brazier J, Beard D, Nazem N, Proctor D. Effects of metronidazole and oligofructose on faecal concentrations of sulphate-reducing bacteria and their activity in human volunteers. Scand J Gastroenterol 2005; 40: 1296-1303.
81. Rahat-Rozenbloom S, Fernandes J, Gloor GB, Wolever TMS. Evidence for greater production of colonic short-chain fatty acids in overweight than lean humans. Int J Obes (Lond) 2014; 38: 1525-1531.
82. Aguirre M, Jonkers DMAE, Troost FJ, Roeselers G, Venema K. In vitro characterization of the impact of different substrates on metabolite production energy extraction and composition of Gut microbiota from lean and obese subjects. PLoS One 2014; 9: 113864.
83. Fava F, Gitau R, Griffin BA, Gibson GR, Tuohy KM, Lovegrove JA. The type and quantity of dietary fat and carbohydrate alter faecal microbiome and short-chain fatty acid excretion in a metabolic syndrome "at-risk" population. Int J Obes (Lond) 2013; 37: 216-223.
84. Mudaliar S, Henry RR, Sanyal AJ etal. Efficacy and safety of the farnesoid x receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology 2013; 145: 574-582.e1.
85. Thomas C, Gioiello A, Noriega L etal. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab 2009; 10: 167-177.
86. Ridlon JM, Kang DJ, Hylemon PB, Bajaj JS. Bile acids and the gut microbiome. Curr Opin Gastroenterol 2014; 30: 332-338.
87. Lefebvre P, Cariou B, Lien F, Kuipers F, Staels B. Role of bile acids and bile acid receptors in metabolic regulation. Physiol Rev 2009; 89: 147-191.
88. Out C, Patankar JV, Doktorova M etal. Gut microbiota inhibit Asbt-dependent intestinal bile acid reabsorption via Gata4. J Hepatol 2015; 63: 697-704.
89. Sayin SI, Wahlström A, Felin J etal. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab 2013; 17: 225-235.
90. Wostmann BS. Intestinal bile acids and cholesterol absorption in the germfree rat. J Nutr 1973; 103: 982-990.
91. Carulli N, Ponz de Leon M, Loria P, Iori R, Rosi A, Romani M. Effect of the selective expansion of cholic acid pool on bile lipid composition: possible mechanism of bile acid induced biliary cholesterol desaturation. Gastroenterology 1981; 81: 539-546.
92. Berr F, Kullak-Ublick GA, Paumgartner G, Munzing W, Hylemon PB. 7 alpha-dehydroxylating bacteria enhance deoxycholic acid input and cholesterol saturation of bile in patients with gallstones. Gastroenterology 1996; 111: 1611-1620.
93. Kurdi P, Kawanishi K, Mizutani K, Yokota A. Mechanism of growth inhibition by free bile acids in lactobacilli and bifidobacteria. J Bacteriol 2006; 188: 1979-1986.
94. Islam KBMS, Fukiya S, Hagio M etal. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology 2011; 141: 1773-1781.
95. Devkota S, Wang Y, Musch MW etal. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice. Nature 2012; 487: 104-108.
96. Hofmann AF, Eckmann L. How bile acids confer gut mucosal protection against bacteria. Proc Natl Acad Sci U S A 2006; 103: 4333-4334.
97. Lorenzo-Zúñiga V, Bartolí R, Planas R etal. Oral bile acids reduce bacterial overgrowth, bacterial translocation, and endotoxemia in cirrhotic rats. Hepatology 2003; 37: 551-557.
98. Bajaj JS, Heuman DM, Hylemon PB etal. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J Hepatol 2014; 60: 940-947.
99. Bauer TM, Schwacha H, Steinbrückner B etal. Small intestinal bacterial overgrowth in human cirrhosis is associated with systemic endotoxemia. Am J Gastroenterol 2002; 97: 2364-2370.
100. Kakiyama G, Pandak WM, Gillevet PM etal. Modulation of the fecal bile acid profile by gut microbiota in cirrhosis. J Hepatol 2013; 58: 949-955.
101. Joyce SA, MacSharry J, Casey PG etal. Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut. Proc Natl Acad Sci U S A 2014; 111: 7421-7426.
102. Nieuwdorp M, Vrieze A, Jonker A etal. Intestinal microbiota is associated with inflamed visceral adipose tissue (Abstract). Diabetologia 2012; 55: S1-S538.
103. Amar J, Serino M, Lange C etal. Involvement of tissue bacteria in the onset of diabetes in humans: evidence for a concept. Diabetologia 2011; 54: 3055-3061.
104. Moreno-Navarrete JM, Escoté X, Ortega F etal. A role for adipocyte-derived lipopolysaccharide-binding protein in inflammation- and obesity-associated adipose tissue dysfunction. Diabetologia 2013; 56: 2524-2537.
105. Koren O, Spor A, Felin J etal. Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc Natl Acad Sci U S A 2011; 108(Suppl. 1): 4592-4598.
106. Van Cromphaut SJ, Vanhorebeek I, de van Berghe GV. Glucose metabolism and insulin resistance in sepsis. Curr Pharm Des 2008; 14: 1887-1899.
107. Amar J, Chabo C, Waget A etal. Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment. EMBO Mol Med 2011; 3: 559-572.
108. Cani PD, Amar J, Iglesias MA etal. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007; 56: 1761-1772.
109. Mehta NN, McGillicuddy FC, Anderson PD etal. Experimental endotoxemia induces adipose inflammation and insulin resistance in humans. Diabetes 2010; 59: 172-181.
110. Ortiz S, Zapater P, Estrada JL etal. Bacterial DNA translocation holds increased insulin resistance and systemic inflammatory levels in morbid obese patients. J Clin Endocrinol Metab 2014; 99: 2573-2585.
111. Membrez M, Blancher F, Jaquet M etal. Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice. FASEB J Off Publ Fed Am Soc Exp Biol 2008; 22: 2416-2426.