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Gut microbiota and obesity

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Abstract

The human intestine harbors a complex bacterial community called the gut microbiota. This microbiota is specific to each individual despite the existence of several bacterial species shared by the majority of adults. The influence of the gut microbiota in human health and disease has been revealed in the recent years. Particularly, the use of germ-free animals and microbiota transplant showed that the gut microbiota may play a causal role in the development of obesity and associated metabolic disorders, and lead to identification of several mechanisms. In humans, differences in microbiota composition, functional genes and metabolic activities are observed between obese and lean individuals suggesting a contribution of the gut microbiota to these phenotypes. Finally, the evidence linking gut bacteria to host metabolism could allow the development of new therapeutic strategies based on gut microbiota modulation to treat or prevent obesity.

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Abbreviations

AMPK:

AMP-activated protein kinase

ANGPTL4:

Angiopoietin-like 4

BSH:

Bile salt hydrolase

DIO:

Diet-induced obesity

eCB:

Endocannabinoïd

FFAR:

Free fatty acid receptor

FMT:

Fecal microbiota transplant

GF:

Germ-free

GI:

Gastro-intestinal

GLP:

Glucagon-like peptide

HFD:

High-fat diet

HGC:

High gene count

IBD:

Inflammatory bowel disease

LGC:

Low gene count

LPL:

Lipoprotein lipase

LPS:

Lipopolysaccharides

PYY:

Peptide YY

SCFA:

Short chain fatty acid

TLR:

Toll-like receptor

TMA:

Trimethylamine

References

  1. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, Abraham JP, Abu-Rmeileh NM, Achoki T, AlBuhairan FS, Alemu ZA, Alfonso R, Ali MK, Ali R, Guzman NA, Ammar W, Anwari P, Banerjee A, Barquera S, Basu S, Bennett DA, Bhutta Z, Blore J, Cabral N, Nonato IC, Chang JC, Chowdhury R, Courville KJ, Criqui MH, Cundiff DK, Dabhadkar KC, Dandona L, Davis A, Dayama A, Dharmaratne SD, Ding EL, Durrani AM, Esteghamati A, Farzadfar F, Fay DF, Feigin VL, Flaxman A, Forouzanfar MH, Goto A, Green MA, Gupta R, Hafezi-Nejad N, Hankey GJ, Harewood HC, Havmoeller R, Hay S, Hernandez L, Husseini A, Idrisov BT, Ikeda N, Islami F, Jahangir E, Jassal SK, Jee SH, Jeffreys M, Jonas JB, Kabagambe EK, Khalifa SE, Kengne AP, Khader YS, Khang YH, Kim D, Kimokoti RW, Kinge JM, Kokubo Y, Kosen S, Kwan G, Lai T, Leinsalu M, Li Y, Liang X, Liu S, Logroscino G, Lotufo PA, Lu Y, Ma J, Mainoo NK, Mensah GA, Merriman TR, Mokdad AH, Moschandreas J, Naghavi M, Naheed A, Nand D, Narayan KM, Nelson EL, Neuhouser ML, Nisar MI, Ohkubo T, Oti SO, Pedroza A, Prabhakaran D, Roy N, Sampson U, Seo H, Sepanlou SG, Shibuya K, Shiri R, Shiue I, Singh GM, Singh JA, Skirbekk V, Stapelberg NJ, Sturua L, Sykes BL, Tobias M, Tran BX, Trasande L, Toyoshima H, van de Vijver S, Vasankari TJ, Veerman JL, Velasquez-Melendez G, Vlassov VV, Vollset SE, Vos T, Wang C, Wang X, Weiderpass E, Werdecker A, Wright JL, Yang YC, Yatsuya H, Yoon J, Yoon SJ, Zhao Y, Zhou M, Zhu S, Lopez AD, Murray CJ, Gakidou E (2014) 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 384(9945):766–781. doi:10.1016/S0140-6736(14)60460-8

    Article  PubMed  PubMed Central  Google Scholar 

  2. Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, Gortmaker SL (2011) The global obesity pandemic: shaped by global drivers and local environments. Lancet 378(9793):804–814. doi:10.1016/S0140-6736(11)60813-1

    Article  PubMed  Google Scholar 

  3. Hill JO (2006) Understanding and addressing the epidemic of obesity: an energy balance perspective. Endocr Rev 27(7):750–761

    Article  PubMed  Google Scholar 

  4. Clavel T, Desmarchelier C, Haller D, Gerard P, Rohn S, Lepage P, Daniel H (2014) Intestinal microbiota in metabolic diseases: from bacterial community structure and functions to species of pathophysiological relevance. Gut Microbes 5(4):544–551. doi:10.4161/gmic.29331

    Article  PubMed  Google Scholar 

  5. Rosenbaum M, Knight R, Leibel RL (2015) The gut microbiota in human energy homeostasis and obesity. Trends Endocrinol Metab 26(9):493–501. doi:10.1016/j.tem.2015.07.002

    Article  PubMed  CAS  Google Scholar 

  6. Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J (2014) The placenta harbors a unique microbiome. Sci Transl Med 6(237):237ra265. doi:10.1126/scitranslmed.3008599

    Article  CAS  Google Scholar 

  7. Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO (2007) Development of the human infant intestinal microbiota. PLoS Biol 5(7):e177

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Koenig JE, Spor A, Scalfone N, Fricker AD, Stombaugh J, Knight R, Angenent LT, Ley RE (2011) Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci USA 108(Suppl 1):4578–4585. doi:10.1073/pnas.1000081107

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Faith JJ, Guruge JL, Charbonneau M, Subramanian S, Seedorf H, Goodman AL, Clemente JC, Knight R, Heath AC, Leibel RL, Rosenbaum M, Gordon JI (2013) The long-term stability of the human gut microbiota. Science 341(6141):1237439. doi:10.1126/science.1237439

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Dethlefsen L, Huse S, Sogin ML, Relman DA (2008) The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol 6(11):e280. doi:10.1371/journal.pbio.0060280

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Dethlefsen L, Relman DA (2011) Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci USA 108(Suppl 1):4554–4561. doi:10.1073/pnas.1000087107

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Zhang C, Zhang M, Wang S, Han R, Cao Y, Hua W, Mao Y, Zhang X, Pang X, Wei C, Zhao G, Chen Y, Zhao L (2010) Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice. ISME J 4(2):232–241. doi:10.1038/ismej.2009.112

    Article  PubMed  CAS  Google Scholar 

  13. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R, Gordon JI (2009) A core gut microbiome in obese and lean twins. Nature 457(7228):480–484

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R (2012) Diversity, stability and resilience of the human gut microbiota. Nature 489(7415):220–230. doi:10.1038/nature11550

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Franzosa EA, Huang K, Meadow JF, Gevers D, Lemon KP, Bohannan BJ, Huttenhower C (2015) Identifying personal microbiomes using metagenomic codes. Proc Natl Acad Sci USA 112(22):E2930–2938. doi:10.1073/pnas.1423854112

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Ley RE, Hamady M, Lozupone C, Turnbaugh PJ, Ramey RR, Bircher JS, Schlegel ML, Tucker TA, Schrenzel MD, Knight R, Gordon JI (2008) Evolution of mammals and their gut microbes. Science 320(5883):1647–1651

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. O’Hara AM, Shanahan F (2006) The gut flora as a forgotten organ. EMBO Rep 7(7):688–693. doi:10.1038/sj.embor.7400731

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Olsen GJ, Lane DJ, Giovannoni SJ, Pace NR, Stahl DA (1986) Microbial ecology and evolution: a ribosomal RNA approach. Annu Rev Microbiol 40:337–365

    Article  PubMed  CAS  Google Scholar 

  19. Gérard P (2011) Le microbiote intestinal: composition et fonctions. Phytothérapie 9(2):72–75

    Article  Google Scholar 

  20. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA (2005) Diversity of the human intestinal microbial flora. Science 308(5728):1635–1638

    Article  PubMed  PubMed Central  Google Scholar 

  21. Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR (2007) Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA 104(34):13780–13785

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Hsiao WW, Fraser-Liggett CM (2009) Human Microbiome Project–paving the way to a better understanding of ourselves and our microbes. Drug Discov Today 14(7–8):331–333

    Article  PubMed  Google Scholar 

  23. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI (2007) The human microbiome project. Nature 449(7164):804–810

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Frank DN, Pace NR (2008) Gastrointestinal microbiology enters the metagenomics era. Curr Opin Gastroenterol 24(1):4–10

    Article  PubMed  CAS  Google Scholar 

  25. Gill SR, Pop M, Deboy RT, Eckburg PB, Turnbaugh PJ, Samuel BS, Gordon JI, Relman DA, Fraser-Liggett CM, Nelson KE (2006) Metagenomic analysis of the human distal gut microbiome. Science 312(5778):1355–1359

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Li J, Jia H, Cai X, Zhong H, Feng Q, Sunagawa S, Arumugam M, Kultima JR, Prifti E, Nielsen T, Juncker AS, Manichanh C, Chen B, Zhang W, Levenez F, Wang J, Xu X, Xiao L, Liang S, Zhang D, Zhang Z, Chen W, Zhao H, Al-Aama JY, Edris S, Yang H, Wang J, Hansen T, Nielsen HB, Brunak S, Kristiansen K, Guarner F, Pedersen O, Dore J, Ehrlich SD, Meta HITC, Bork P, Wang J, Meta HITC (2014) An integrated catalog of reference genes in the human gut microbiome. Nat Biotechnol 32(8):834–841. doi:10.1038/nbt.2942

    Article  PubMed  CAS  Google Scholar 

  27. Dethlefsen L, McFall-Ngai M, Relman DA (2007) An ecological and evolutionary perspective on human-microbe mutualism and disease. Nature 449(7164):811–818

    Article  PubMed  CAS  Google Scholar 

  28. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Li S, Jian M, Zhou Y, Li Y, Zhang X, Li S, Qin N, Yang H, Wang J, Brunak S, Dore J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J, Bork P, Ehrlich SD, Wang J (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464(7285):59–65

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto JM, Bertalan M, Borruel N, Casellas F, Fernandez L, Gautier L, Hansen T, Hattori M, Hayashi T, Kleerebezem M, Kurokawa K, Leclerc M, Levenez F, Manichanh C, Nielsen HB, Nielsen T, Pons N, Poulain J, Qin J, Sicheritz-Ponten T, Tims S, Torrents D, Ugarte E, Zoetendal EG, Wang J, Guarner F, Pedersen O, de Vos WM, Brunak S, Dore J, Antolin M, Artiguenave F, Blottiere HM, Almeida M, Brechot C, Cara C, Chervaux C, Cultrone A, Delorme C, Denariaz G, Dervyn R, Foerstner KU, Friss C, van de Guchte M, Guedon E, Haimet F, Huber W, van Hylckama-Vlieg J, Jamet A, Juste C, Kaci G, Knol J, Lakhdari O, Layec S, Le Roux K, Maguin E, Merieux A, Melo Minardi R, M’Rini C, Muller J, Oozeer R, Parkhill J, Renault P, Rescigno M, Sanchez N, Sunagawa S, Torrejon A, Turner K, Vandemeulebrouck G, Varela E, Winogradsky Y, Zeller G, Weissenbach J, Ehrlich SD, Bork P (2011) Enterotypes of the human gut microbiome. Nature 473(7346):174–180. doi:10.1038/nature09944

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, Bewtra M, Knights D, Walters WA, Knight R, Sinha R, Gilroy E, Gupta K, Baldassano R, Nessel L, Li H, Bushman FD, Lewis JD (2011) Linking long-term dietary patterns with gut microbial enterotypes. Science 334(6052):105–108. doi:10.1126/science.1208344

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Knights D, Ward TL, McKinlay CE, Miller H, Gonzalez A, McDonald D, Knight R (2014) Rethinking “enterotypes”. Cell Host Microbe 16(4):433–437. doi:10.1016/j.chom.2014.09.013

    Article  PubMed  CAS  Google Scholar 

  32. Backhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI (2005) Host-bacterial mutualism in the human intestine. Science 307(5717):1915–1920

    Article  PubMed  CAS  Google Scholar 

  33. Hooper LV, Midtvedt T, Gordon JI (2002) How host-microbial interactions shape the nutrient environment of the mammalian intestine. Annu Rev Nutr 22:283–307

    Article  PubMed  CAS  Google Scholar 

  34. Gérard P, Bernalier-Donadille A (2007) Les fonctions majeures du microbiote intestinal. Cahiers de Nutrition et de Diététique 42:S28–S36

    Article  Google Scholar 

  35. Backhed F, Fraser CM, Ringel Y, Sanders ME, Sartor RB, Sherman PM, Versalovic J, Young V, Finlay BB (2012) Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications. Cell Host Microbe 12(5):611–622. doi:10.1016/j.chom.2012.10.012

    Article  PubMed  CAS  Google Scholar 

  36. Duca F, Gerard P, Covasa M, Lepage P (2014) Metabolic interplay between gut bacteria and their host. Front Horm Res 42:73–82. doi:10.1159/000358315

    Article  PubMed  Google Scholar 

  37. Le Roy T, Llopis M, Lepage P, Bruneau A, Rabot S, Bevilacqua C, Martin P, Philippe C, Walker F, Bado A, Perlemuter G, Cassard-Doulcier A, Gérard P (2013) Intestinal microbiota determines development of nonalcoholic fatty liver disease in mice. Gut 62(12):1787–1794

    Article  PubMed  CAS  Google Scholar 

  38. Mayer EA, Tillisch K, Gupta A (2015) Gut/brain axis and the microbiota. J Clin Invest 125(3):926–938. doi:10.1172/JCI76304

    Article  PubMed  Google Scholar 

  39. Wostmann BS, Larkin C, Moriarty A, Bruckner-Kardoss E (1983) Dietary intake, energy metabolism, and excretory losses of adult male germfree Wistar rats. Lab Anim Sci 33(1):46–50

    PubMed  CAS  Google Scholar 

  40. Backhed 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 USA 101(44):15718–15723

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Backhed F, Manchester JK, Semenkovich CF, Gordon JI (2007) Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci USA 104(3):979–984

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Rabot S, Membrez M, Bruneau A, Gérard P, Harach T, Moser M, Raymond F, Mansourian R, Chou CJ (2010) Germ-free C57BL/6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolism. FASEB J 24(12):4948–4959

    Article  PubMed  CAS  Google Scholar 

  43. Fleissner CK, Huebel N, Abd El-Bary MM, Loh G, Klaus S, Blaut M (2010) Absence of intestinal microbiota does not protect mice from diet-induced obesity. Br J Nutr 104(6):919–929. doi:10.1017/S0007114510001303

    Article  PubMed  CAS  Google Scholar 

  44. Swartz TD, Sakar Y, Duca FA, Covasa M (2013) Preserved adiposity in the Fischer 344 rat devoid of gut microbiota. FASEB J 27(4):1701–1710. doi:10.1096/fj.12-221689

    Article  PubMed  CAS  Google Scholar 

  45. Flint HJ, Bayer EA, Rincon MT, Lamed R, White BA (2008) Polysaccharide utilization by gut bacteria: potential for new insights from genomic analysis. Nat Rev Microbiol 6(2):121–131

    Article  PubMed  CAS  Google Scholar 

  46. Stappenbeck TS, Hooper LV, Gordon JI (2002) Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc Natl Acad Sci USA 99(24):15451–15455

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Conterno L, Fava F, Viola R, Tuohy KM (2011) Obesity and the gut microbiota: does up-regulating colonic fermentation protect against obesity and metabolic disease? Genes Nutr 6(3):241–260. doi:10.1007/s12263-011-0230-1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Brown AJ, Goldsworthy SM, Barnes AA, Eilert MM, Tcheang L, Daniels D, Muir AI, Wigglesworth MJ, Kinghorn I, Fraser NJ, Pike NB, Strum JC, Steplewski KM, Murdock PR, Holder JC, Marshall FH, Szekeres PG, Wilson S, Ignar DM, Foord SM, Wise A, Dowell SJ (2003) The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 278(13):11312–11319. doi:10.1074/jbc.M211609200

    Article  PubMed  CAS  Google Scholar 

  49. Bjursell M, Admyre T, Goransson M, Marley AE, Smith DM, Oscarsson J, Bohlooly YM (2011) 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 300(1):E211–220. doi:10.1152/ajpendo.00229.2010

    Article  PubMed  CAS  Google Scholar 

  50. 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 USA 105(43):16767–16772

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Cani PD, Dewever C, Delzenne NM (2004) Inulin-type fructans modulate gastrointestinal peptides involved in appetite regulation (glucagon-like peptide-1 and ghrelin) in rats. Br J Nutr 92(3):521–526

    Article  PubMed  CAS  Google Scholar 

  52. Cani PD, Lecourt E, Dewulf EM, Sohet FM, Pachikian BD, Naslain D, De Backer F, Neyrinck AM, Delzenne NM (2009) 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 90(5):1236–1243. doi:10.3945/ajcn.2009.28095

    Article  PubMed  CAS  Google Scholar 

  53. Tarini J, Wolever TM (2010) 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 35(1):9–16. doi:10.1139/H09-119

    Article  PubMed  CAS  Google Scholar 

  54. 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. doi:10.1186/1475-2859-10-S1-S10

    Article  PubMed  PubMed Central  Google Scholar 

  55. Soliman MM, Ahmed MM, Salah-Eldin AE, Abdel-Aal AA (2011) Butyrate regulates leptin expression through different signaling pathways in adipocytes. J Vet Sci 12(4):319–323

    Article  PubMed  PubMed Central  Google Scholar 

  56. Lin HV, Frassetto A, Kowalik EJ Jr, Nawrocki AR, Lu MM, Kosinski JR, Hubert JA, Szeto D, Yao X, Forrest G, Marsh DJ (2012) Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One 7(4):e35240. doi:10.1371/journal.pone.0035240

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Moore PR, Evenson A et al (1946) Use of sulfasuxidine, streptothricin, and streptomycin in nutritional studies with the chick. J Biol Chem 165(2):437–441

    PubMed  CAS  Google Scholar 

  58. Coates ME, Fuller R, Harrison GF, Lev M, Suffolk SF (1963) A comparison of the growth of chicks in the Gustafsson germ-free apparatus and in a conventional environment, with and without dietary supplements of penicillin. Br J Nutr 17:141–150

    Article  PubMed  CAS  Google Scholar 

  59. Gaskins HR, Collier CT, Anderson DB (2002) Antibiotics as growth promotants: mode of action. Anim Biotechnol 13(1):29–42. doi:10.1081/ABIO-120005768

    Article  PubMed  CAS  Google Scholar 

  60. Cho I, Yamanishi S, Cox L, Methe BA, Zavadil J, Li K, Gao Z, Mahana D, Raju K, Teitler I, Li H, Alekseyenko AV, Blaser MJ (2012) Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature 488(7413):621–626. doi:10.1038/nature11400

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Cox LM, Yamanishi S, Sohn J, Alekseyenko AV, Leung JM, Cho I, Kim SG, Li H, Gao Z, Mahana D, Zarate Rodriguez JG, Rogers AB, Robine N, Loke P, Blaser MJ (2014) Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell 158(4):705–721. doi:10.1016/j.cell.2014.05.052

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Cox LM, Blaser MJ (2015) Antibiotics in early life and obesity. Nat Rev Endocrinol 11(3):182–190. doi:10.1038/nrendo.2014.210

    Article  PubMed  PubMed Central  Google Scholar 

  63. Membrez M, Blancher F, Jaquet M, Bibiloni R, Cani PD, Burcelin RG, Corthesy I, Mace K, Chou CJ (2008) Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice. FASEB J 22(7):2416–2426

    Article  PubMed  CAS  Google Scholar 

  64. Haight TH, Pierce WE (1955) Effect of prolonged antibiotic administration of the weight of healthy young males. J Nutr 56(1):151–161

    PubMed  CAS  Google Scholar 

  65. Ozawa E (1955) Studies on growth promotion by antibiotics. II. Results of aurofac administration to infants. J Antibiot 8(6):212–214

    PubMed  CAS  Google Scholar 

  66. Ajslev TA, Andersen CS, Gamborg M, Sorensen TI, Jess T (2011) 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) 35(4):522–529. doi:10.1038/ijo.2011.27

    Article  CAS  Google Scholar 

  67. Bailey LC, Forrest CB, Zhang P, Richards TM, Livshits A, DeRusso PA (2014) Association of antibiotics in infancy with early childhood obesity. JAMA Pediatr 168(11):1063–1069. doi:10.1001/jamapediatrics.2014.1539

    Article  PubMed  Google Scholar 

  68. Murphy R, Stewart AW, Braithwaite I, Beasley R, Hancox RJ, Mitchell EA, Group IPTS (2014) Antibiotic treatment during infancy and increased body mass index in boys: an international cross-sectional study. Int J Obes (Lond) 38(8):1115–1119. doi:10.1038/ijo.2013.218

    Article  Google Scholar 

  69. Trasande L, Blustein J, Liu M, Corwin E, Cox LM, Blaser MJ (2013) Infant antibiotic exposures and early-life body mass. Int J Obes (Lond) 37(1):16–23. doi:10.1038/ijo.2012.132

    Article  CAS  Google Scholar 

  70. Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 102(31):11070–11075

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Ley RE, Turnbaugh PJ, Klein S, Gordon JI (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444(7122):1022–1023

    Article  PubMed  CAS  Google Scholar 

  72. Armougom F, Henry M, Vialettes B, Raccah D, Raoult D (2009) Monitoring bacterial community of human gut microbiota reveals an increase in Lactobacillus in obese patients and methanogens in anorexic patients. PLoS One 4(9):e7125. doi:10.1371/journal.pone.0007125

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Furet JP, Kong LC, Tap J, Poitou C, Basdevant A, Bouillot JL, Mariat D, Corthier G, Dore J, Henegar C, Rizkalla S, Clement K (2010) Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes 59(12):3049–3057. doi:10.2337/db10-0253

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Santacruz A, Collado MC, Garcia-Valdes L, Segura MT, Martin-Lagos JA, Anjos T, Marti-Romero M, Lopez RM, Florido J, Campoy C, Sanz Y (2010) Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women. Br J Nutr 104(1):83–92. doi:10.1017/S0007114510000176

    Article  PubMed  CAS  Google Scholar 

  75. Collado MC, Isolauri E, Laitinen K, Salminen S (2008) Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am J Clin Nutr 88(4):894–899

    PubMed  CAS  Google Scholar 

  76. Duncan SH, Lobley GE, Holtrop G, Ince J, Johnstone AM, Louis P, Flint HJ (2008) Human colonic microbiota associated with diet, obesity and weight loss. Int J Obes (Lond) 32(11):1720–1724

    Article  CAS  Google Scholar 

  77. Jumpertz R, Le DS, Turnbaugh PJ, Trinidad C, Bogardus C, Gordon JI, Krakoff J (2011) Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am J Clin Nutr 94(1):58–65. doi:10.3945/ajcn.110.010132

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Schwiertz A, Taras D, Schafer K, Beijer S, Bos NA, Donus C, Hardt PD (2010) Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring) 18(1):190–195

    Article  Google Scholar 

  79. Million M, Angelakis E, Paul M, Armougom F, Leibovici L, Raoult D (2012) Comparative meta-analysis of the effect of Lactobacillus species on weight gain in humans and animals. Microb Pathog 53(2):100–108. doi:10.1016/j.micpath.2012.05.007

    Article  PubMed  Google Scholar 

  80. Kalliomaki M, Collado MC, Salminen S, Isolauri E (2008) Early differences in fecal microbiota composition in children may predict overweight. Am J Clin Nutr 87(3):534–538

    PubMed  CAS  Google Scholar 

  81. Yin YN, Yu QF, Fu N, Liu XW, Lu FG (2010) Effects of four Bifidobacteria on obesity in high-fat diet induced rats. World J Gastroenterol 16(27):3394–3401

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Kozyrskyj AL, Kalu R, Koleva PT, Bridgman SL (2015) Fetal programming of overweight through the microbiome: boys are disproportionately affected. J Dev Orig Health Dis. doi:10.1017/S2040174415001269

    PubMed  Google Scholar 

  83. Fei N, Zhao L (2013) An opportunistic pathogen isolated from the gut of an obese human causes obesity in germfree mice. ISME J 7(4):880–884. doi:10.1038/ismej.2012.153

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermudez-Humaran LG, Gratadoux JJ, Blugeon S, Bridonneau C, Furet JP, Corthier G, Grangette C, Vasquez N, Pochart P, Trugnan G, Thomas G, Blottiere HM, Dore J, Marteau P, Seksik P, Langella P (2008) Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci USA 105(43):16731–16736

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Cao Y, Shen J, Ran ZH (2014) Association between Faecalibacterium prausnitzii reduction and inflammatory bowel disease: a meta-analysis and systematic review of the literature. Gastroenterol Res Pract 2014:872725. doi:10.1155/2014/872725

    PubMed  PubMed Central  Google Scholar 

  86. Dao MC, Everard A, Aron-Wisnewsky J, Sokolovska N, Prifti E, Verger EO, Kayser BD, Levenez F, Chilloux J, Hoyles L, Consortium MI-O, Dumas ME, Rizkalla SW, Dore J, Cani PD, Clement K (2015) Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. doi:10.1136/gutjnl-2014-308778

    Google Scholar 

  87. Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y, Derrien M, Muccioli GG, Delzenne NM, de Vos WM, Cani PD (2013) Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci USA 110(22):9066–9071. doi:10.1073/pnas.1219451110

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. 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(7122):1027–1031

    Article  PubMed  Google Scholar 

  89. 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 USA 109(2):594–599. doi:10.1073/pnas.1116053109

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Schwiertz A, Taras D, Schafer K, Beijer S, Bos NA, Donus C, Hardt PD (2010) Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring) 18(1):190–195. doi:10.1038/oby.2009.167

    Article  Google Scholar 

  91. Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, Almeida M, Arumugam M, Batto JM, Kennedy S, Leonard P, Li J, Burgdorf K, Grarup N, Jorgensen T, Brandslund I, Nielsen HB, Juncker AS, Bertalan M, Levenez F, Pons N, Rasmussen S, Sunagawa S, Tap J, Tims S, Zoetendal EG, Brunak S, Clement K, Dore J, Kleerebezem M, Kristiansen K, Renault P, Sicheritz-Ponten T, de Vos WM, Zucker JD, Raes J, Hansen T, Bork P, Wang J, Ehrlich SD, Pedersen O, Guedon E, Delorme C, Layec S, Khaci G, van de Guchte M, Vandemeulebrouck G, Jamet A, Dervyn R, Sanchez N, Maguin E, Haimet F, Winogradski Y, Cultrone A, Leclerc M, Juste C, Blottiere H, Pelletier E, LePaslier D, Artiguenave F, Bruls T, Weissenbach J, Turner K, Parkhill J, Antolin M, Manichanh C, Casellas F, Boruel N, Varela E, Torrejon A, Guarner F, Denariaz G, Derrien M, van Hylckama Vlieg JE, Veiga P, Oozeer R, Knol J, Rescigno M, Brechot C, M’Rini C, Merieux A, Yamada T (2013) Richness of human gut microbiome correlates with metabolic markers. Nature 500(7464):541–546. doi:10.1038/nature12506

    Article  PubMed  CAS  Google Scholar 

  92. Cotillard A, Kennedy SP, Kong LC, Prifti E, Pons N, Le Chatelier E, Almeida M, Quinquis B, Levenez F, Galleron N, Gougis S, Rizkalla S, Batto JM, Renault P, Dore J, Zucker JD, Clement K, Ehrlich SD, Blottiere H, Leclerc M, Juste C, de Wouters T, Lepage P, Fouqueray C, Basdevant A, Henegar C, Godard C, Fondacci M, Rohia A, Hajduch F, Weissenbach J, Pelletier E, Le Paslier D, Gauchi JP, Gibrat JF, Loux V, Carre W, Maguin E, van de Guchte M, Jamet A, Boumezbeur F, Layec S (2013) Dietary intervention impact on gut microbial gene richness. Nature 500(7464):585–588. doi:10.1038/nature12480

    Article  PubMed  CAS  Google Scholar 

  93. Mondot S, de Wouters T, Dore J, Lepage P (2013) The human gut microbiome and its dysfunctions. Dig Dis 31(3–4):278–285. doi:10.1159/000354678

    Article  PubMed  Google Scholar 

  94. Turnbaugh PJ, Backhed F, Fulton L, Gordon JI (2008) Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3(4):213–223

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI (2009) The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med 1 (6):6ra14

  96. Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, Griffin NW, Lombard V, Henrissat B, Bain JR, Muehlbauer MJ, Ilkayeva O, Semenkovich CF, Funai K, Hayashi DK, Lyle BJ, Martini MC, Ursell LK, Clemente JC, Van Treuren W, Walters WA, Knight R, Newgard CB, Heath AC, Gordon JI (2013) Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341(6150):1241214. doi:10.1126/science.1241214

    Article  PubMed  CAS  Google Scholar 

  97. Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, Srinivasan S, Sitaraman SV, Knight R, Ley RE, Gewirtz AT (2010) Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 328(5975):228–231

    Article  PubMed  CAS  Google Scholar 

  98. Di Luccia B, Crescenzo R, Mazzoli A, Cigliano L, Venditti P, Walser JC, Widmer A, Baccigalupi L, Ricca E, Iossa S (2015) Rescue of fructose-induced metabolic syndrome by antibiotics or faecal transplantation in a rat model of obesity. PLoS One 10(8):e0134893. doi:10.1371/journal.pone.0134893

    Article  PubMed  PubMed Central  Google Scholar 

  99. Hotamisligil GS (2006) Inflammation and metabolic disorders. Nature 444(7121):860–867

    Article  PubMed  CAS  Google Scholar 

  100. Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmee E, Cousin B, Sulpice T, Chamontin B, Ferrieres J, Tanti JF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56(7):1761–1772

    Article  PubMed  CAS  Google Scholar 

  101. Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC (1990) CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249(4975):1431–1433

    Article  PubMed  CAS  Google Scholar 

  102. Neal MD, Leaphart C, Levy R, Prince J, Billiar TR, Watkins S, Li J, Cetin S, Ford H, Schreiber A, Hackam DJ (2006) Enterocyte TLR4 mediates phagocytosis and translocation of bacteria across the intestinal barrier. J Immunol 176(5):3070–3079

    Article  PubMed  CAS  Google Scholar 

  103. Vreugdenhil AC, Rousseau CH, Hartung T, Greve JW, van ‘t Veer C, Buurman WA (2003) Lipopolysaccharide (LPS)-binding protein mediates LPS detoxification by chylomicrons. J Immunol 170(3):1399–1405

    Article  PubMed  CAS  Google Scholar 

  104. Creely SJ, McTernan PG, Kusminski CM, Fisher M, Da Silva NF, Khanolkar M, Evans M, Harte AL, Kumar S (2007) Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am J Physiol Endocrinol Metab 292(3):E740–747

    Article  PubMed  CAS  Google Scholar 

  105. Harte AL, da Silva NF, Creely SJ, McGee KC, Billyard T, Youssef-Elabd EM, Tripathi G, Ashour E, Abdalla MS, Sharada HM, Amin AI, Burt AD, Kumar S, Day CP, McTernan PG (2010) Elevated endotoxin levels in non-alcoholic fatty liver disease. J Inflamm (Lond) 7:15

    Article  CAS  Google Scholar 

  106. Davis JE, Gabler NK, Walker-Daniels J, Spurlock ME (2008) Tlr-4 deficiency selectively protects against obesity induced by diets high in saturated fat. Obesity (Silver Spring) 16(6):1248–1255

    Article  CAS  Google Scholar 

  107. Tsukumo DM, Carvalho-Filho MA, Carvalheira JB, Prada PO, Hirabara SM, Schenka AA, Araujo EP, Vassallo J, Curi R, Velloso LA, Saad MJ (2007) Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance. Diabetes 56(8):1986–1998

    Article  PubMed  CAS  Google Scholar 

  108. Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R (2008) Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57(6):1470–1481

    Article  PubMed  CAS  Google Scholar 

  109. Wang Z, Xiao G, Yao Y, Guo S, Lu K, Sheng Z (2006) The role of bifidobacteria in gut barrier function after thermal injury in rats. J Trauma 61(3):650–657

    Article  PubMed  Google Scholar 

  110. Griffiths EA, Duffy LC, Schanbacher FL, Qiao H, Dryja D, Leavens A, Rossman J, Rich G, Dirienzo D, Ogra PL (2004) In vivo effects of bifidobacteria and lactoferrin on gut endotoxin concentration and mucosal immunity in Balb/c mice. Dig Dis Sci 49(4):579–589

    Article  PubMed  CAS  Google Scholar 

  111. Cani PD, Neyrinck AM, Fava F, Knauf C, Burcelin RG, Tuohy KM, Gibson GR, Delzenne NM (2007) Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia 50(11):2374–2383

    Article  PubMed  CAS  Google Scholar 

  112. Cani PD, Possemiers S, Van de Wiele T, Guiot Y, Everard A, Rottier O, Geurts L, Naslain D, Neyrinck A, Lambert DM, Muccioli GG, Delzenne NM (2009) Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 58(8):1091–1103. doi:10.1136/gut.2008.165886

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. Geurts L, Lazarevic V, Derrien M, Everard A, Van Roye M, Knauf C, Valet P, Girard M, Muccioli GG, Francois P, de Vos WM, Schrenzel J, Delzenne NM, Cani PD (2011) Altered gut microbiota and endocannabinoid system tone in obese and diabetic leptin-resistant mice: impact on apelin regulation in adipose tissue. Front Microbiol 2:149. doi:10.3389/fmicb.2011.00149

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  114. Muccioli GG, Naslain D, Backhed F, Reigstad CS, Lambert DM, Delzenne NM, Cani PD (2010) The endocannabinoid system links gut microbiota to adipogenesis. Mol Syst Biol 6:392. doi:10.1038/msb.2010.46

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Everard A, Geurts L, Caesar R, Van Hul M, Matamoros S, Duparc T, Denis RG, Cochez P, Pierard F, Castel J, Bindels LB, Plovier H, Robine S, Muccioli GG, Renauld JC, Dumoutier L, Delzenne NM, Luquet S, Backhed F, Cani PD (2014) Intestinal epithelial MyD88 is a sensor switching host metabolism towards obesity according to nutritional status. Nat Commun 5:5648. doi:10.1038/ncomms6648

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. Amar J, Chabo C, Waget A, Klopp P, Vachoux C, Bermudez-Humaran LG, Smirnova N, Berge M, Sulpice T, Lahtinen S, Ouwehand A, Langella P, Rautonen N, Sansonetti PJ, Burcelin R (2011) Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment. EMBO Mol Med 3(9):559–572. doi:10.1002/emmm.201100159

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  117. Amar J, Serino M, Lange C, Chabo C, Iacovoni J, Mondot S, Lepage P, Klopp C, Mariette J, Bouchez O, Perez L, Courtney M, Marre M, Klopp P, Lantieri O, Dore J, Charles M, Balkau B, Burcelin R, Group DESIRS (2011) Involvement of tissue bacteria in the onset of diabetes in humans: evidence for a concept. Diabetologia 54(12):3055–3061. doi:10.1007/s00125-011-2329-8

    Article  PubMed  CAS  Google Scholar 

  118. Burcelin R, Serino M, Chabo C, Garidou L, Pomie C, Courtney M, Amar J, Bouloumie A (2013) Metagenome and metabolism: the tissue microbiota hypothesis. Diabetes Obes Metab 15(Suppl 3):61–70. doi:10.1111/dom.12157

    Article  PubMed  CAS  Google Scholar 

  119. Wostmann BS (1973) Intestinal bile acids and cholesterol absorption in the germfree rat. J Nutr 103(7):982–990

    PubMed  CAS  Google Scholar 

  120. Wostmann BS, Wiech NL (1961) Total serum and liver cholesterol in germfree and conventional male rats. Am J Physiol 201:1027–1029

    PubMed  CAS  Google Scholar 

  121. Velagapudi VR, Hezaveh R, Reigstad CS, Gopalacharyulu P, Yetukuri L, Islam S, Felin J, Perkins R, Boren J, Oresic M, Backhed F (2010) The gut microbiota modulates host energy and lipid metabolism in mice. J Lipid Res 51(5):1101–1112. doi:10.1194/jlr.M002774

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  122. Gérard P, Lepercq P, Leclerc M, Gavini F, Raibaud P, Juste C (2007) Bacteroides sp. strain D8, the first cholesterol-reducing bacterium isolated from human feces. Appl Environ Microbiol 73(18):5742–5749

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Parmentier G, Eyssen H (1974) Mechanism of biohydrogenation of cholesterol to coprostanol by Eubacterium ATCC 21408. Biochim Biophys Acta 348(2):279–284

    Article  PubMed  CAS  Google Scholar 

  124. Sekimoto H, Shimada O, Makanishi M, Nakano T, Katayama O (1983) Interrelationship between serum and fecal sterols. Jpn J Med 22(1):14–20

    Article  PubMed  CAS  Google Scholar 

  125. Gérard P (2009) GI tract: microbial metabolism of steroids. In: Timmis KN (ed) Microbiology of hydrocarbons, oils, lipids, and derived compounds, vol 4. Springer, Heidelberg, pp 3133–3140

    Google Scholar 

  126. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL (2011) Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472(7341):57–63

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  127. Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL (2013) Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 368(17):1575–1584. doi:10.1056/NEJMoa1109400

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  128. Gérard P (2014) Metabolism of cholesterol and bile acids by the gut microbiota. Pathogens 3(1):14–24. doi:10.3390/pathogens3010014

    Article  PubMed Central  CAS  Google Scholar 

  129. Joyce SA, Shanahan F, Hill C, Gahan CG (2014) Bacterial bile salt hydrolase in host metabolism: potential for influencing gastrointestinal microbe-host crosstalk. Gut Microbes 5(5):669–674. doi:10.4161/19490976.2014.969986

    Article  PubMed  PubMed Central  Google Scholar 

  130. Kondo S, Xiao JZ, Satoh T, Odamaki T, Takahashi S, Sugahara H, Yaeshima T, Iwatsuki K, Kamei A, Abe K (2010) Antiobesity effects of Bifidobacterium breve strain B-3 supplementation in a mouse model with high-fat diet-induced obesity. Biosci Biotechnol Biochem 74(8):1656–1661. doi:10.1271/bbb.100267

    Article  PubMed  CAS  Google Scholar 

  131. An HM, Park SY, Lee do K, Kim JR, Cha MK, Lee SW, Lim HT, Kim KJ, Ha NJ (2011) Antiobesity and lipid-lowering effects of Bifidobacterium spp. in high fat diet-induced obese rats. Lipids Health Dis 10:116. doi:10.1186/1476-511X-10-116

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Chen J, Wang R, Li XF, Wang RL (2012) Bifidobacterium adolescentis supplementation ameliorates visceral fat accumulation and insulin sensitivity in an experimental model of the metabolic syndrome. Br J Nutr 107(10):1429–1434. doi:10.1017/S0007114511004491

    Article  PubMed  CAS  Google Scholar 

  133. Chen JJ, Wang R, Li XF, Wang RL (2011) Bifidobacterium longum supplementation improved high-fat-fed-induced metabolic syndrome and promoted intestinal Reg I gene expression. Exp Biol Med 236(7):823–831. doi:10.1258/ebm.2011.010399

    Article  CAS  Google Scholar 

  134. Cano PG, Santacruz A, Trejo FM, Sanz Y (2013) Bifidobacterium CECT 7765 improves metabolic and immunological alterations associated with obesity in high-fat diet-fed mice. Obesity (Silver Spring) 21(11):2310–2321. doi:10.1002/oby.20330

    Article  CAS  Google Scholar 

  135. Moya-Perez A, Neef A, Sanz Y (2015) Bifidobacterium pseudocatenulatum CECT 7765 reduces obesity-associated inflammation by restoring the lymphocyte-macrophage balance and gut microbiota structure in high-fat diet-fed mice. PLoS One 10(7):e0126976. doi:10.1371/journal.pone.0126976

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  136. Lee HY, Park JH, Seok SH, Baek MW, Kim DJ, Lee KE, Paek KS, Lee Y, Park JH (2006) Human originated bacteria, Lactobacillus rhamnosus PL60, produce conjugated linoleic acid and show anti-obesity effects in diet-induced obese mice. Biochim Biophys Acta 1761(7):736–744. doi:10.1016/j.bbalip.2006.05.007

    Article  PubMed  CAS  Google Scholar 

  137. Lee K, Paek K, Lee HY, Park JH, Lee Y (2007) Antiobesity effect of trans-10, cis-12-conjugated linoleic acid-producing Lactobacillus plantarum PL62 on diet-induced obese mice. J Appl Microbiol 103(4):1140–1146. doi:10.1111/j.1365-2672.2007.03336.x

    Article  PubMed  CAS  Google Scholar 

  138. Hamad EM, Sato M, Uzu K, Yoshida T, Higashi S, Kawakami H, Kadooka Y, Matsuyama H, Abd El-Gawad IA, Imaizumi K (2009) Milk fermented by Lactobacillus gasseri SBT2055 influences adipocyte size via inhibition of dietary fat absorption in Zucker rats. Br J Nutr 101(5):716–724. doi:10.1017/S0007114508043808

    Article  PubMed  CAS  Google Scholar 

  139. Aronsson L, Huang Y, Parini P, Korach-Andre M, Hakansson J, Gustafsson JA, Pettersson S, Arulampalam V, Rafter J (2010) Decreased fat storage by Lactobacillus paracasei is associated with increased levels of angiopoietin-like 4 protein (ANGPTL4). PLoS One 5(9). doi:10.1371/journal.pone.0013087

  140. Okubo T, Takemura N, Yoshida A, Sonoyama K (2013) KK/Ta mice administered Lactobacillus plantarum strain no. 14 have lower adiposity and higher insulin sensitivity. Biosci Microbiota Food Health 32(3):93–100. doi:10.12938/bmfh.32.93

    Article  PubMed  PubMed Central  Google Scholar 

  141. Fak F, Backhed F (2012) Lactobacillus reuteri prevents diet-induced obesity, but not atherosclerosis, in a strain dependent fashion in Apoe−/− mice. PLoS One 7(10):e46837. doi:10.1371/journal.pone.0046837

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Kim SW, Park KY, Kim B, Kim E, Hyun CK (2013) Lactobacillus rhamnosus GG improves insulin sensitivity and reduces adiposity in high-fat diet-fed mice through enhancement of adiponectin production. Biochem Biophys Res Commun 431(2):258–263. doi:10.1016/j.bbrc.2012.12.121

    Article  PubMed  CAS  Google Scholar 

  143. Wang LX, Liu K, Gao DW, Hao JK (2013) Protective effects of two Lactobacillus plantarum strains in hyperlipidemic mice. World J Gastroenterol 19(20):3150–3156. doi:10.3748/wjg.v19.i20.3150

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  144. Tomaro-Duchesneau C, Saha S, Malhotra M, Jones ML, Labbe A, Rodes L, Kahouli I, Prakash S (2014) Effect of orally administered L. fermentum NCIMB 5221 on markers of metabolic syndrome: an in vivo analysis using ZDF rats. Appl Microbiol Biotechnol 98(1):115–126. doi:10.1007/s00253-013-5252-8

    Article  PubMed  CAS  Google Scholar 

  145. Park KY, Kim B, Hyun CK (2015) Lactobacillus rhamnosus GG reverses insulin resistance but does not block its onset in diet-induced obese mice. J Microbiol Biotechnol 25(5):753–757

    PubMed  CAS  Google Scholar 

  146. Martin FP, Wang Y, Sprenger N, Yap IK, Lundstedt T, Lek P, Rezzi S, Ramadan Z, van Bladeren P, Fay LB, Kochhar S, Lindon JC, Holmes E, Nicholson JK (2008) Probiotic modulation of symbiotic gut microbial-host metabolic interactions in a humanized microbiome mouse model. Mol Syst Biol 4:157. doi:10.1038/msb4100190

    PubMed  PubMed Central  Google Scholar 

  147. Park YH, Kim JG, Shin YW, Kim SH, Whang KY (2007) Effect of dietary inclusion of Lactobacillus acidophilus ATCC 43121 on cholesterol metabolism in rats. J Microbiol Biotechnol 17(4):655–662

    PubMed  CAS  Google Scholar 

  148. Kadooka Y, Sato M, Imaizumi K, Ogawa A, Ikuyama K, Akai Y, Okano M, Kagoshima M, Tsuchida T (2010) Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial. Eur J Clin Nutr 64(6):636–643. doi:10.1038/ejcn.2010.19

    Article  PubMed  CAS  Google Scholar 

  149. Kadooka Y, Sato M, Ogawa A, Miyoshi M, Uenishi H, Ogawa H, Ikuyama K, Kagoshima M, Tsuchida T (2013) Effect of Lactobacillus gasseri SBT2055 in fermented milk on abdominal adiposity in adults in a randomised controlled trial. Br J Nutr 110(9):1696–1703. doi:10.1017/S0007114513001037

    Article  PubMed  CAS  Google Scholar 

  150. Ogawa A, Kadooka Y, Kato K, Shirouchi B, Sato M (2014) Lactobacillus gasseri SBT2055 reduces postprandial and fasting serum non-esterified fatty acid levels in Japanese hypertriacylglycerolemic subjects. Lipids Health Dis 13:36. doi:10.1186/1476-511X-13-36

    Article  PubMed  PubMed Central  Google Scholar 

  151. Floch MH (2014) Recommendations for probiotic use in humans—a 2014 update. Pharmaceuticals 7(10):999–1007. doi:10.3390/ph7100999

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  152. Roberfroid M, Gibson GR, Hoyles L, McCartney AL, Rastall R, Rowland I, Wolvers D, Watzl B, Szajewska H, Stahl B, Guarner F, Respondek F, Whelan K, Coxam V, Davicco MJ, Leotoing L, Wittrant Y, Delzenne NM, Cani PD, Neyrinck AM, Meheust A (2010) Prebiotic effects: metabolic and health benefits. Br J Nutr 104(Suppl 2):S1–63. doi:10.1017/S0007114510003363

    Article  PubMed  CAS  Google Scholar 

  153. Everard A, Lazarevic V, Derrien M, Girard M, Muccioli GG, Neyrinck AM, Possemiers S, Van Holle A, Francois P, de Vos WM, Delzenne NM, Schrenzel J, Cani PD (2011) Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes 60(11):2775–2786. doi:10.2337/db11-0227

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  154. Neyrinck AM, Possemiers S, Druart C, Van de Wiele T, De Backer F, Cani PD, Larondelle Y, Delzenne NM (2011) Prebiotic effects of wheat arabinoxylan related to the increase in bifidobacteria, Roseburia and Bacteroides/Prevotella in diet-induced obese mice. PLoS One 6(6):e20944. doi:10.1371/journal.pone.0020944

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  155. Parnell JA, Reimer RA (2012) Prebiotic fibres dose-dependently increase satiety hormones and alter Bacteroidetes and Firmicutes in lean and obese JCR:LA-cp rats. Br J Nutr 107(4):601–613. doi:10.1017/S0007114511003163

    Article  PubMed  CAS  Google Scholar 

  156. Everard A, Lazarevic V, Gaia N, Johansson M, Stahlman M, Backhed F, Delzenne NM, Schrenzel J, Francois P, Cani PD (2014) Microbiome of prebiotic-treated mice reveals novel targets involved in host response during obesity. ISME J 8(10):2116–2130. doi:10.1038/ismej.2014.45

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  157. Respondek F, Gerard P, Bossis M, Boschat L, Bruneau A, Rabot S, Wagner A, Martin JC (2013) Short-chain fructo-oligosaccharides modulate intestinal microbiota and metabolic parameters of humanized gnotobiotic diet induced obesity mice. PLoS One 8(8):e71026. doi:10.1371/journal.pone.0071026

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  158. Cani PD, Daubioul CA, Reusens B, Remacle C, Catillon G, Delzenne NM (2005) Involvement of endogenous glucagon-like peptide-1(7-36) amide on glycaemia-lowering effect of oligofructose in streptozotocin-treated rats. J Endocrinol 185(3):457–465. doi:10.1677/joe.1.06100

    Article  PubMed  CAS  Google Scholar 

  159. Cani PD, Neyrinck AM, Maton N, Delzenne NM (2005) Oligofructose promotes satiety in rats fed a high-fat diet: involvement of glucagon-like peptide-1. Obes Res 13(6):1000–1007. doi:10.1038/oby.2005.117

    Article  PubMed  CAS  Google Scholar 

  160. Chassaing B, Miles-Brown JP, Pellizzon M, Ulman E, Ricci M, Zhang L, Patterson AD, Vijay-Kumar M, Gewirtz AT (2015) Lack of soluble fiber drives diet-induced adiposity in mice. Am J Physiol Gastrointest Liver Physiol 00172:02015. doi:10.1152/ajpgi.00172.2015

    Google Scholar 

  161. Cani PD, Joly E, Horsmans Y, Delzenne NM (2006) Oligofructose promotes satiety in healthy human: a pilot study. Eur J Clin Nutr 60(5):567–572. doi:10.1038/sj.ejcn.1602350

    Article  PubMed  CAS  Google Scholar 

  162. Dewulf EM, Cani PD, Claus SP, Fuentes S, Puylaert PG, Neyrinck AM, Bindels LB, de Vos WM, Gibson GR, Thissen JP, Delzenne NM (2013) Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women. Gut 62(8):1112–1121. doi:10.1136/gutjnl-2012-303304

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  163. Genta S, Cabrera W, Habib N, Pons J, Carillo IM, Grau A, Sanchez S (2009) Yacon syrup: beneficial effects on obesity and insulin resistance in humans. Clin Nutr 28(2):182–187. doi:10.1016/j.clnu.2009.01.013

    Article  PubMed  CAS  Google Scholar 

  164. Kellow NJ, Coughlan MT, Reid CM (2014) Metabolic benefits of dietary prebiotics in human subjects: a systematic review of randomised controlled trials. Br J Nutr 111(7):1147–1161. doi:10.1017/S0007114513003607

    Article  PubMed  CAS  Google Scholar 

  165. Parnell JA, Reimer RA (2009) Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Am J Clin Nutr 89(6):1751–1759. doi:10.3945/ajcn.2009.27465

    Article  PubMed  CAS  Google Scholar 

  166. Aroniadis OC, Brandt LJ (2013) Fecal microbiota transplantation: past, present and future. Curr Opin Gastroenterol 29(1):79–84. doi:10.1097/MOG.0b013e32835a4b3e

    Article  PubMed  Google Scholar 

  167. Eiseman B, Silen W, Bascom GS, Kauvar AJ (1958) Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery 44(5):854–859

    PubMed  CAS  Google Scholar 

  168. Kassam Z, Lee CH, Yuan Y, Hunt RH (2013) Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol 108(4):500–508. doi:10.1038/ajg.2013.59

    Article  PubMed  Google Scholar 

  169. Vrieze A, Van Nood E, Holleman F, Salojarvi J, Kootte RS, Bartelsman JF, Dallinga-Thie GM, Ackermans MT, Serlie MJ, Oozeer R, Derrien M, Druesne A, Van Hylckama Vlieg JE, Bloks VW, Groen AK, Heilig HG, Zoetendal EG, Stroes ES, de Vos WM, Hoekstra JB, Nieuwdorp M (2012) Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 143(4):913–916 e917. doi:10.1053/j.gastro.2012.06.031

    Article  PubMed  CAS  Google Scholar 

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  1. INRA, UMR1319 MICALIS, Equipe AMIPEM, Building 442, Domaine de Vilvert, 78350, Jouy-en-Josas, France

    Philippe Gérard

  2. AgroParisTech, UMR MICALIS, 78350, Jouy-en-Josas, France

    Philippe Gérard

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Gérard, P. Gut microbiota and obesity. Cell. Mol. Life Sci. 73, 147–162 (2016). https://doi.org/10.1007/s00018-015-2061-5

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