The journey of gut microbiome – An introduction and its influence on metabolic disorders

Abstract

BACKGROUND: Metabolic disorders such as Obesity, Diabetes Type 2 (T2DM) and Inflammatory Bowel Diseases (IBD) are the most prevalent globally. Recently, there has been a surge in the evidence indicating the correlation between the intestinal microbiota and development of these metabolic conditions apart from predisposing genetic and epigenetic factors. Gut microbiome is pivotal in controlling the host metabolism and physiology. But imbalances in the microbiota patterns lead to these disorders via several pathways. Animal and human studies so far have concentrated mostly on metagenomics for the whole microbiome characterization to understand how microbiome supports health in general. However, the accurate mechanisms connecting the metabolic disorders and alterations in gut microbial composition in host and the metabolites employed by the microorganisms in regulating the metabolic disorders is still vague.

OBJECTIVE: The review delineates the latest findings about the role of gut microbiome to the pathophysiology of Obesity, IBD and Diabetes Mellitus. Here, we provide a brief introduction to the gut microbiome followed by the current therapeutic interventions in restoration of the disrupted intestinal microbiota.

METHODS: A methodical PubMed search was performed using keywords like “gut microbiome,” “obesity,” “diabetes,” “IBD,” and “metabolic syndromes.” All significant and latest publications up to January 2018 were accounted for the review.

RESULTS: Out of the 93 articles cited, 63 articles focused on the gut microbiota association to these disorders. The rest 18 literature outlines the therapeutic approaches in maintaining the gut homeostasis using probiotics, prebiotics and faecal microbial transplant (FMT).

CONCLUSION: Metabolic disorders have intricate etiology and thus a lucid understanding of the complex host-microbiome inter-relationships will open avenues to novel therapeutics for the diagnosis, prevention and treatment of the metabolic diseases.

Key words： gut microbiome; metabolic disorders; obesity; diabetes type 2; inflammatorybowel diseases; probiotics; prebiotics; FMT

Conflicts of interest

There are no conflicts of interest between the authors.

References

1 Aas J, Gessert C E, Bakken J S (2003). Recurrent Clostridium difficile colitis: case series involving 18 patients treated with donor stool administered via a nasogastric tube. Clin Infect Dis, 36(5): 580–585

PMID

2 Adlerberth I, Wold A E (2009). Establishment of the gut microbiota in Western infants. Acta Paediatr, 98(2): 229–238

PMID

3 Allen J M, Mailing L J, Niemiro G M, Moore R, Cook M D, White B A, Holscher H D, Woods J A(2018).Exercise Alters Gut Microbiota Composition and Function in Lean and Obese Humans. Med Sci Sports Exerc, 50(4): 747–757.doi:10.1249/MSS.0000000000001495

PMID

4 Aw W, Fukuda S (2018). Understanding the role of the gut ecosystem in diabetes mellitus. J Diabetes Investig, 9(1): 5–12

PMID

5 Bäckhed F, Ding H, Wang T, Hooper L V, Koh G Y, Nagy A, Semenkovich C F, Gordon J I (2004). The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA, 101(44): 15718–15723

PMID

6 Bäckhed F, Ley R E, Sonnenburg J L, Peterson D A, Gordon J I (2005). Host-bacterial mutualism in the human intestine. Science, 307(5717): 1915–1920

PMID

7 Bäckhed F, Roswall J, Peng Y, Feng Q, Jia H, Kovatcheva-Datchary P, Li Y, Xia Y, Xie H, Zhong H, Khan M T, Zhang J, Li J, Xiao L, Al-Aama J, Zhang D, Lee Y S, Kotowska D, Colding C, Tremaroli V, Yin Y, Bergman S, Xu X, Madsen L, Kristiansen K, Dahlgren J, Wang J (2015). Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life. Cell Host Microbe, 17(5):690–703doi:10.1016/j.chom.2015.05.012

8 Barlow G M, Yu A, Mathur R (2015). Role of the Gut Microbiome in Obesity and Diabetes Mellitus. Nutr Clin Pract, 30(6): 787–797

PMID

9 Bevins C L, Salzman N H (2011). Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat Rev Microbiol, 9(5): 356–368

PMID

10 Boulangé C L, Neves A L, Chilloux J, Nicholson J K, Dumas M E (2016). Impact of the gut microbiota on inflammation, obesity, and metabolic disease. Genome Med, 8(1): 1-12

PMID

11 Brunkwall L, Orho-Melander M (2017). The gut microbiome as a target for prevention and treatment of hyperglycaemia in type 2 diabetes: from current human evidence to future possibilities. Diabetologia, 60(6): 943–951

PMID

12 Calças N, Mendonça L, Perez L, Ferreira R, Elisei C, Castro A (2017). Diet as a Therapy for Gut Dysbacteriosis. JSM Biochem Mol Biol, 4(1): 102, pp. 1–6.

13 Cani P D (2013). Gut microbiota and obesity: lessons from the microbiome. Brief Funct Genomics, 12(4): 381–387

PMID

14 Cani P D, Delzenne N M (2009). The role of the gut microbiota in energy metabolism and metabolic disease. Curr Pharm Des, 15(13): 1546–1558

PMID

15 Cani P D, Knauf C, Iglesias M A, Drucker D J, Delzenne N M, Burcelin R (2006). Improvement of glucose tolerance and hepatic insulin sensitivity by oligofructose requires a functional glucagon-like peptide 1 receptor. Diabetes, 55(5): 1484–1490

PMID

16 Cani P D, Lecourt E, Dewulf E M, Sohet F M, Pachikian B D, Naslain D, De Backer F, Neyrinck A M, Delzenne N M (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

PMID

17 Cani P D, Neyrinck A M, Fava F, Knauf C, Burcelin R G, Tuohy K M, Gibson G R, Delzenne N M (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

PMID

18 Catalán V, Gómez-Ambrosi J, Ramirez B, Rotellar F, Pastor C, Silva C, Rodríguez A, Gil M J, Cienfuegos J A, Frühbeck G (2007). Proinflammatory cytokines in obesity: impact of type 2 diabetes mellitus and gastric bypass. Obes Surg, 17(11): 1464–1474

PMID

19 Cénit M C, Matzaraki V, Tigchelaar E F, Zhernakova A (2014). Rapidly expanding knowledge on the role of the gut microbiome in health and disease. Biochim Biophys Acta, 1842(10): 1981–1992

PMID

20 Claesson MJ, Cusack S, O'Sullivan O, Greene-Diniz R, de Weerd H, Flannery E, Marchesi JR, Falush D, Dinan T, Fitzgerald G, Stanton C, van Sinderen D, O'Connor M, Harnedy N, O'Connor K, Henry C, O'Mahony D, Fitzgerald AP, Shanahan F, Twomey C, Hill C, Ross RP, O'Toole PW(2011). Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci USA, 108(Suppl 1): 4586–4591

PMID

21 Clarke S F, Murphy E F, Nilaweera K, Ross P R, Shanahan F, O’Toole P W, Cotter P D (2012). The gut microbiota and its relationship to diet and obesity. Gut Microbes, 3(3): 186–202

PMID

22 Couturier-Maillard A, Secher T, Rehman A, Normand S, De Arcangelis A, Haesler R, Huot L, Grandjean T, Bressenot A, Delanoye-Crespin A, Gaillot O, Schreiber S, Lemoine Y, Ryffel B, Hot D, Nùñez G, Chen G, Rosenstiel P, Chamaillard M (2013). NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer. J Clin Invest, 123(2): 700–711

PMID

23 D’Argenio V, Salvatore F (2015). The role of the gut microbiome in the healthy adult status. Clin Chim Acta, 451(Pt A): 97–102

PMID

24 D’Aversa F, Tortora A, Ianiro G, Ponziani F R, Annicchiarico B E, Gasbarrini A (2013). Gut microbiota and metabolic syndrome. Intern Emerg Med, 8(S1Suppl 1): 11–S15

PMID

25 Dahiya D K, Renuka , Puniya M, Shandilya U K, Dhewa T, Kumar N, Kumar S, Puniya A K, Shukla P (2017). Gut Microbiota Modulation and Its Relationship with Obesity Using Prebiotic Fibers and Probiotics: A Review. Front Microbiol, 8(April): Article-563, pp. 3-17

PMID

26 Delaere F, Duchampt A, Mounien L, Seyer P, Duraffourd C, Zitoun C, Thorens B, Mithieux G (2013). The role of sodium-coupled glucose co-transporter 3 in the satiety effect of portal glucose sensing. Mol Metab, 2(1): 47–53

PMID

27 Delzenne N M, Neyrinck A M, Bäckhed F, Cani P D (2011). Targeting gut microbiota in obesity: effects of prebiotics and probiotics. Nat Rev Endocrinol, 7(11): 639–646

PMID

28 Devaraj S, Hemarajata P, Versalovic J (2013). The human gut microbiome and body metabolism: implications for obesity and diabetes. Clin Chem, 59(4): 617–628

PMID

29 Dominguez-Bello M G, Costello E K, Contreras M, Magris M, Hidalgo G, Fierer N, Knight R (2010). Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci USA, 107(26): 11971–11975

PMID

30 Donnet-Hughes A, Perez P F, Doré J, Leclerc M, Levenez F, Benyacoub J, Serrant P, Segura-Roggero I, Schiffrin E J (2010). Potential role of the intestinal microbiota of the mother in neonatal immune education. Proc Nutr Soc, 69(03):407–415

PMID

31 Donohoe D R, Wali A, Brylawski B P, Bultman S J (2012). Microbial regulation of glucose metabolism and cell-cycle progression in mammalian colonocytes. PLoS One, 7(9): e46589

PMID

32 Elson C O, Cong Y (2012). Host-microbiota interactions in inflammatory bowel disease. Gut Microbes, 3(4): 332–344

PMID

33 Fessler M B, Rudel L L, Brown J M (2009). Toll-like receptor signaling links dietary fatty acids to the metabolic syndrome. Curr Opin Lipidol, 20(5): 379–385

PMID

34 Fluitman K S, Clercq N CD, Keijser B J F, Visser M, Nieuwdorp M, IJzerman R G (2017). The intestinal microbiota, energy balance, and malnutrition: emphasis on the role of short-chain fatty acids. Expert Rev Endocrinol Metab, 12(3): 215–226

35 Forslund K, Hildebrand F, Nielsen T, Falony G, Le Chatelier E, Sunagawa S, Prifti E, Vieira-Silva S, Gudmundsdottir V, Pedersen H K, Arumugam M, Kristiansen K, Voigt A Y, Vestergaard H, Hercog R, Costea P I, Kultima J R, Li J, Jørgensen T, Levenez F, Dore J, MetaHIT consortium, Nielsen H B, Brunak S, Raes J, Hansen T, Wang J, Ehrlich S D, Bork P, Pedersen O, Almeida M, Antolin M, Artiguenave F, Batto JM, Bertalan M, Blottière H, Boruel N, Brechot C, Bruls T, Burgdorf K, Casellas F, Cultrone A, de Vos WM, Delorme C, Denariaz G, Derrien M, Dervyn R, Feng Q, Grarup N, Guarner F, Guedon E, Haimet F, Jamet A, Juncker A, Juste C, Kennedy S, KhaciG, Kleerebezem M, Knoll J, Layec S, Leclerc M, Leonard P, LePaslier D, M'Rini C, Maguin E, Manichanh C, Mende D, Mérieux A, Oozeer R, Parkhill J, Pelletier E, Pons N, Qin J, Rasmussen S, Renault P, Rescigno M, Sanchez N, Sicheritz-Ponten T, Tap J, Tims S, Torrejon A, Turner K, van de Guchte M, van Hylckama Vlieg JE, Vandemeulebrouck G, Varela E, Viega P, Weissenbach J, Winogradski Y, Yamada T, Zoetendal EG (2015). Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature, 528(7581): 262–266

PMID

36 Frank D N, Amand A L St,Feldman R A, Boedeker E C, Harpaz N, Pace N R (2007). Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA, 104(34): 13780–13785

PMID

37 Furet J P, Kong L C, Tap J, Poitou C, Basdevant A, Bouillot J L, Mariat D, Corthier G, Doré J, Henegar C, Rizkalla S, Clément 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

PMID

38 Gevers D, Knight R, Petrosino J F, Huang K, McGuire A L, Birren B W, Nelson K E, White O, Methé B A, Huttenhower C (2012). The Human Microbiome Project: a community resource for the healthy human microbiome. PLoS Biol, 10(8): e1001377

PMID

39 Hager C L, Ghannoum M A (2017). The mycobiome: Role in health and disease, and as a potential probiotic target in gastrointestinal disease. Dig Liver Dis, 49(11): 1171–1176

PMID

40 Hansen R, Russell R K, Reiff C, Louis P, McIntosh F, Berry S H, Mukhopadhya I, Bisset W M, Barclay A R, Bishop J, Flynn D M, McGrogan P, Loganathan S, Mahdi G, Flint H J, El-Omar E M, Hold G L (2012). Microbiota of de-novo pediatric IBD: increased Faecalibacterium prausnitzii and reduced bacterial diversity in Crohn’s but not in ulcerative colitis. Am J Gastroenterol, 107(12): 1913–1922

PMID

41 Hartstra A V, Bouter K E, Bäckhed F, Nieuwdorp M (2015). Insights into the role of the microbiome in obesity and type 2 diabetes. Diabetes Care, 38(1): 159–165

PMID

42 Heisel T, Montassier E, Johnson A, Al-Ghalith G, Lin Y W, Wei L N, Knights D, Gale C A (2017). High-fat diet changes fungal microbiomes and interkingdom relationships in the murine gut. MSphere, 2(5): e00351–17

PMID

43 Hinzey E M, R D, L DN (2016). Firmicutes and Bacteroidetes. Nutrition 411, 8–11. Retrieved from:http://www.nutrition411.com/articles/firmicutes-and-bacteroidetes

44 Ho P, Ross D A (2017). More Than a Gut Feeling: The Implications of the Gut Microbiota in Psychiatry. Biol Psychiatry, 81(5): e35–e37

PMID

45 Holleran G, Lopetuso L R, Ianiro G, Pecere S, Pizzoferrato M, Petito V, Graziani C, McNamara D, Gasbarrini A, Scaldaferri F (2017). Gut microbiota and inflammatory bowel disease: so far so gut! Minerva Gastroenterol Dietol, 63(4): 373–384

PMID

46 Human Microbiome Project Consortium, Huttenhower C, Gevers D, Knight R, Abubucker S, Badger J H, Chinwalla A T, Creasy H H, Earl A M, FitzGerald M G, Fulton R S, Giglio M G, Hallsworth-Pepin K, Lobos E A, Madupu R, Magrini V, Martin J C, Mitreva M, Muzny D M, Sodergren E J, Versalovic J, Wollam A M, Worley K C, Wortman J R, Young S K, Zeng Q, Aagaard K M, Abolude O O, Allen-Vercoe E, Alm E J, Alvarado L, Andersen G L, Anderson S, Appelbaum E, Arachchi H M, Armitage G, Arze C A, Ayvaz T, Baker C C, Begg L, Belachew T, Bhonagiri V, Bihan M, Blaser M J, Bloom T, Bonazzi V, Paul Brooks J, Buck G A, Buhay C J, Busam D A, Campbell J L, Canon S R, Cantarel B L, Chain P S G, Chen I M A, Chen L, Chhibba S, Chu K, Ciulla D M, Clemente J C, Clifton S W, Conlan S, Crabtree J, Cutting M A, Davidovics N J, Davis C C, DeSantis T Z, Deal C, Delehaunty K D, Dewhirst F E, Deych E, Ding Y, Dooling D J, Dugan S P, Michael Dunne W, Scott Durkin A, Edgar R C, Erlich R L, Farmer C N, Farrell R M, Faust K, Feldgarden M, Felix V M, Fisher S, Fodor A A, Forney L J, Foster L, Di Francesco V, Friedman J, Friedrich D C, Fronick C C, Fulton L L, Gao H, Garcia N, Giannoukos G, Giblin C, Giovanni M Y, Goldberg J M, Goll J, Gonzalez A, Griggs A, Gujja S, Kinder Haake S, Haas B J, Hamilton H A, Harris E L, Hepburn T A, Herter B, Hoffmann D E, Holder M E, Howarth C, Huang K H, Huse S M, Izard J, Jansson J K, Jiang H, Jordan C, Joshi V, Katancik J A, Keitel W A, Kelley S T, Kells C, King N B, Knights D, Kong H H, Koren O, Koren S, Kota K C, Kovar C L, Kyrpides N C, La Rosa P S, Lee S L, Lemon K P, Lennon N, Lewis C M, Lewis L, Ley R E, Li K, Liolios K, Liu B, Liu Y, Lo C C, Lozupone C A, Dwayne Lunsford R, Madden T, Mahurkar A A, Mannon P J, Mardis E R, Markowitz V M, Mavromatis K, McCorrison J M, McDonald D, McEwen J, McGuire A L, McInnes P, Mehta T, Mihindukulasuriya K A, Miller J R, Minx P J, Newsham I, Nusbaum C, O’Laughlin M, Orvis J, Pagani I, Palaniappan K, Patel S M, Pearson M, Peterson J, Podar M, Pohl C, Pollard K S, Pop M, Priest M E, Proctor L M, Qin X, Raes J, Ravel J, Reid J G, Rho M, Rhodes R, Riehle K P, Rivera M C, Rodriguez-Mueller B, Rogers Y H, Ross M C, Russ C, Sanka R K, Sankar P, Fah Sathirapongsasuti J, Schloss J A, Schloss P D, Schmidt T M, Scholz M, Schriml L, Schubert A M, Segata N, Segre J A, Shannon W D, Sharp R R, Sharpton T J, Shenoy N, Sheth N U, Simone G A, Singh I, Smillie C S, Sobel J D, Sommer D D, Spicer P, Sutton G G, Sykes S M, Tabbaa D G, Thiagarajan M, Tomlinson C M, Torralba M, Treangen T J, Truty R M, Vishnivetskaya T A, Walker J, Wang L, Wang Z, Ward D V, Warren W, Watson M A, Wellington C, Wetterstrand K A, White J R, Wilczek-Boney K, Wu Y Q, Wylie K M, Wylie T, Yandava C, Ye L, Ye Y, Yooseph S, Youmans B P, Zhang L, Zhou Y, Zhu Y, Zoloth L, Zucker J D, Birren B W, Gibbs R A, Highlander S K, Methé B A, Nelson K E, Petrosino J F, Weinstock G M, Wilson R K, White O, and the (2012). Structure, function and diversity of the healthy human microbiome. Nature, 486(7402): 207–214

PMID

47 Hur K Y, Lee M S (2015). Gut Microbiota and Metabolic Disorders. Diabetes Metab J, 39(3): 198–203

PMID

48 Inohara N, Ogura Y, Fontalba A, Gutierrez O, Pons F, Crespo J, Fukase K, Inamura S, Kusumoto S, Hashimoto M, Foster S J, Moran A P, Fernandez-Luna J L, Nuñez G (2003). Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn’s disease. J Biol Chem, 278(8): 5509–5512

PMID

49 Jakobsson H E, Abrahamsson T R, Jenmalm M C, Harris K, Quince C, Jernberg C, Björkstén B, Engstrand L, Andersson A F (2014). Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section. Gut, 63(4): 559–566

PMID

50 Jovel J, Patterson J, Wang W, Hotte N, O'Keefe S, Mitchel T, Perry T, Kao D, Mason AL, Madsen KL, Wong GK (2016). Characterization of the Gut Microbiome Using 16S or Shotgun Metagenomics. Front Microbiol, 7:459, 1–17

51 Karlsson F H, Tremaroli V, Nookaew I, Bergström G, Behre C J, Fagerberg B, Nielsen J, Bäckhed F(2013). Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature, 498(7452): 99–103

52 Khor B, Gardet A, Xavier R J (2011). Genetics and pathogenesis of inflammatory bowel disease. Nature, 474(7351): 307–317

PMID

53 Khoruts A, Dicksved J, Jansson J K, Sadowsky M J (2010). Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea. J Clin Gastroenterol, 44(5): 354–360

PMID

54 Koenig J E, Spor A, Scalfone N, Fricker A D, Stombaugh J, Knight R, Angenent L T, Ley R E (2011). Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci USA, 108(Suppl 1): 4578–4585

PMID

55 Komaroff A L (2017). The microbiome and risk for obesity and diabetes. JAMA, 317(4): 355–356

PMID

56 Kumar R, Yi N, Zhi D, Eipers P, Goldsmith K T, Dixon P, Crossman D K, Crowley M R, Lefkowitz E J, Rodriguez J M, Morrow C D (2017). Identification of donor microbe species that colonize and persist long term in the recipient after fecal transplant for recurrentClostridium difficile. NPJ Biofilms Microbiomes, 3(1): 12

PMID

57 Larsson E, Tremaroli V, Lee YS, Koren O, Nookaew I, Fricker A, Nielsen J, Ley RE, Bäckhed F (2012). Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through MyD88. Gut, 61(8):1124–31

PMID

58 Larsen N, Vogensen FK, van den Berg FWJ, Nielsen DS, Andreasen AS, Pedersen BK, Al-Soud WA, Sørensen SJ, Hansen LH, Jakobsen M (2010). Gut Microbiota in Human Adults with Type 2 Diabetes Differs from Non-Diabetic Adults. PLoS ONE 5:e9085

59 Le Barz M, Anhê F F, Varin T V, Desjardins Y, Levy E, Roy D, Urdaci M C, Marette A (2015). Probiotics as Complementary Treatment for Metabolic Disorders. Diabetes Metab J, 39(4): 291–303

PMID

60 Lederberg J, McCray A T (2001). ‘Ome Sweet ’Omics- A Genealogical Treasury of Words Genealogical Treasury of Words. Scientist, 15(7): 8. Available at:https://lhncbc.nlm.nih.gov/publication/lhncbc-2001-047

61 Leeuwenhoek A Van (1683). An abstract of a Letter from Antonie van Leeuwenhoek, Sep. 12, 1683. About Animals in the scrurf of the Teeth. Philosophical Transactions of the Royal Society of London,14: 568–574.

62 Lepage P, Häsler R, Spehlmann M E, Rehman A, Zvirbliene A, Begun A, Ott S, Kupcinskas L, Doré J, Raedler A, Schreiber S (2011). Twin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitis. Gastroenterology, 141(1): 227–236

PMID

63 Ley R E, Bäckhed F, Turnbaugh P, Lozupone C A, Knight R D, Gordon J I (2005). Obesity alters gut microbial ecology. Proc Natl Acad Sci USA, 102(31): 11070–11075

PMID

64 Ley R E, Turnbaugh P J, Klein S, Gordon J I (2006). Microbial ecology: human gut microbes associated with obesity. Nature, 444(7122): 1022–1023

PMID

65 Li X, Qin L (2005). Metagenomics-based drug discovery and marine microbial diversity. Trends Biotechnol, 23(11):539–43

PMID

66 Machiels K, Joossens M, Sabino J, De Preter V, Arijs I, Eeckhaut V, Ballet V, Claes K, Van Immerseel F, Verbeke K, Ferrante M, Verhaegen J, Rutgeerts P, Vermeire S (2014). A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut, 63(8): 1275–1283

PMID

67 Marchesi J R (2010). Prokaryotic and eukaryotic diversity of the human gut. Adv Appl Microbiol, 72, 43–62

PMID

68 Matsuoka K, Kanai T (2015). The gut microbiota and inflammatory bowel disease. Semin Immunopathol, 37(1): 47–55

PMID

69 McIlroy J, Ianiro G, Mukhopadhya I, Hansen R, Hold G L (2018). Review article: the gut microbiome in inflammatory bowel disease-avenues for microbial management. Aliment Pharmacol Ther, 47(1): 26–42

PMID

70 Methé B A, Nelson K E, Pop M, Creasy H H, Giglio M G, Huttenhower C, Gevers D, Petrosino J F, Abubucker S, Badger J H, Chinwalla A T, Earl A M, FitzGerald M G, Fulton R S, Hallsworth-Pepin K, Lobos EA, Madupu R, Magrini V, Martin J C, Mitreva M, Muzny D M, SodergrenE J, Versalovic J, Wollam A M, Worley K C, Wortman J R, Young S K, Zeng Q, Aagaard K M, Abolude O O, Allen-Vercoe E, Alm E J, Alvarado L, Andersen G L, Anderson S, Appelbaum E, Arachchi H M, Armitage G, Arze C A, Ayvaz T, Baker C C, Begg L, Belachew T, Bhonagiri V, Bihan M, Blaser M J, Bloom T, Bonazzi V R, Brooks P, Buck G A, Buhay C J, Busam D A, Campbell J L, Canon S R, Cantarel B L, Chain P S, Chen I M, Chen L, Chhibba S, Chu K, Ciulla D M, Clemente J C, Clifton S W, Conlan S, Crabtree J, Cutting M A, Davidovics N J, Davis C C, DeSantis T Z, Deal C, Delehaunty K D, Dewhirst F E, Deych E, Ding Y, Dooling D J, Dugan S P, Dunne W Jr, Durkin A, Edgar R C, Erlich R L, Farmer C N, Farrell R M, Faust K, Feldgarden M, Felix V M, Fisher S, Fodor A A, Forney L, Foster L, Di Francesco V, Friedman J, Friedrich D C, Fronick C C, Fulton L L, Gao H, Garcia N, Giannoukos G, Giblin C, Giovanni M Y, Goldberg J M, Goll J, Gonzalez A, Griggs A, Gujja S, Haas B J, Hamilton H A, Harris EL, Hepburn T A, Herter B, Hoffmann D E, Holder M E, Howarth C, Huang K H, Huse S M, Izard J, Jansson J K, Jiang H, Jordan C, Joshi V, Katancik J A, Keitel W A, Kelley S T, Kells C, Kinder-Haake S, King N B, Knight R, Knights D, Kong H H, Koren O, Koren S, Kota K C, Kovar C L, Kyrpides N C, La Rosa P S, Lee S L, Lemon K P, Lennon N, Lewis C M, Lewis L, Ley R E, Li K, Liolios K, Liu B, Liu Y, Lo C C, Lozupone C A, Lunsford R, Madden T, Mahurkar A A, Mannon P J, Mardis E R, Markowitz V M, Mavrommatis K, McCorrison J M, McDonald D, McEwen J, McGuire A L, McInnes P, Mehta T, Mihindukulasuriya K A, Miller J R, Minx P J, Newsham I, Nusbaum C, O'Laughlin M, Orvis J, Pagani I, Palaniappan K, Patel S M, Pearson M, Peterson J, Podar M, Pohl C, Pollard K S, Priest M E, Proctor L M, Qin X, Raes J, Ravel J, Reid J G, Rho M, Rhodes R, Riehle K P, Rivera M C, Rodriguez-Mueller B, Rogers Y H, Ross M C, Russ C, Sanka R K, Sankar P, Sathirapongsasuti J, Schloss J A, Schloss P D, Schmidt T M, Scholz M, Schriml L, Schubert A M, Segata N, Segre J A, Shannon W D, Sharp R R, Sharpton T J, Shenoy N, Sheth N U, Simone G A, Singh I, Smillie C S, Sobel J D, Sommer D D, Sommer P, Sutton G G, Sykes S M, Tabbaa D G, Thiagarajan M, Tomlinson C M, Torralba M, Treangen T J, Truty R M, Vishnivetskaya T A, Walker J, Wang L, Wang Z, Ward D V, Warren W, Watson M A, Wellington C, Wetterstrand K A, White J R, Wilczek-Boney K, Wu Y Q, Wylie K M, Wylie T, Yandava C, Ye L, Ye Y, Yooseph S, Youmans B P, Zhang L, Zhou Y, Zhu Y, Zoloth L, Zucker J D, Birren B W, Gibbs R A, Highlander S K, Weinstock G M, Wilson R K, White O (2012). A framework for human microbiome. Nature, 486(7402): 215-S

71 Morgan X C, Tickle T L, Sokol H, Gevers D, Devaney K L, Ward D V, Reyes J A, Shah S A, LeLeiko N, Snapper S B, Bousvaros A, Korzenik J, Sands B E, Xavier R J, Huttenhower C (2012). Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol, 13(9): R79

PMID

72 O’Hara A M, Shanahan F (2006). The gut flora as a forgotten organ. EMBO Rep, 7(7): 688–693

PMID

73 Ogura Y, Bonen D K, Inohara N, Nicolae D L, Chen F F, Ramos R, Britton H, Moran T, Karaliuskas R, Duerr R H, Achkar J P, Brant S R, Bayless T M, Kirschner B S, Hanauer S B, Nuñez G, Cho J H (2001). A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature, 411(6837): 603–606

PMID

74 Pace N R, Stahl D A, Lane D J, Olsen G J (1986). The Analysis of Natural Microbial Populations by Ribosomal RNA Sequences. Adv Microb Ecol, 9: 1–55

75 Palmer C, Bik E M, DiGiulio D B, Relman D A, Brown P O (2007). Development of the human infant intestinal microbiota. PLoS Biol, 5(7): e177

PMID

76 Park D Y, Ahn Y T, Park S H, Huh C S, Yoo S R, Yu R, Sung M K, McGregor R A, Choi M S (2013). Supplementation of Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 in diet-induced obese mice is associated with gut microbial changes and reduction in obesity. PLoS One, 8(3): e59470

PMID

77 Björkstén A E, Gosalbes M J, Friedrichs A, Knecht H, Artacho A, Eismann K, Otto W, Rojo D, Bargiela R, von Bergen M, Neulinger S C, Däumer C, Heinsen F A, Latorre A, Barbas C, Seifert J, dos Santos V M, Ott S J, Ferrer M, Moya A (2013). Gut microbiota disturbance during antibiotic therapy: a multi-omic approach. Gut, 62(11): 1591–1601

PMID

78 Perry R J, Peng L, Barry N A, Cline G W, Zhang D, Cardone R L, Petersen K F, Kibbey R G, Goodman A L, Shulman G I (2016). Acetate mediates a microbiome-brain--cell axis to promote metabolic syndrome. Nature, 534(7606): 213–217

PMID

79 The NIH HMP Working Group, Peterson J, Garges S, Giovanni M, McInnes P, Wang L, Schloss JA, Bonazzi V, McEwen JE, Wetterstrand KA, Deal C, Baker CC, Di Francesco V, Howcroft TK, Karp RW, Lunsford RD, Wellington CR, Belachew T, Wright M, Giblin C, David H, Mills M, Salomon R, Mullins C, Akolkar B, Begg L, Davis C, Grandison L, Humble M, Khalsa J, Little AR, Peavy H, Pontzer C, Portnoy M, Sayre MH, Starke-Reed P, Zakhari S, Read J, Watson B, Guyer M (2009). The NIH Human Microbiome Project. Genome Res, 19(12): 2317–2323

PMID

80 Petnicki-Ocwieja T, Hrncir T, Liu Y J, Biswas A, Hudcovic T, Tlaskalova-Hogenova H, Kobayashi K S (2009). Nod2 is required for the regulation of commensal microbiota in the intestine. Proc Natl Acad Sci USA, 106(37): 15813–15818

PMID

81 Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, Liang S, Zhang W, Guan Y, Shen D, Peng Y, Zhang D, Jie Z, Wu W, Qin Y, Xue W, Li J, Han L, Lu D, Wu P, Dai Y, Sun X, Li Z, Tang A, Zhong S, Li X, Chen W, Xu R, Wang M, Feng Q, Gong M, Yu J, Zhang Y, Zhang M, Hansen T, Sanchez G, Raes J, Falony G, Okuda S, Almeida M, LeChatelier E, Renault P, Pons N, Batto JM, Zhang Z, Chen H, Yang R, Zheng W, Li S, Yang H, Wang J, Ehrlich SD, Nielsen R, Pedersen O, Kristiansen K, Wang J(2012). A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature, 490(7418): 55–60

PMID

82 Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende D R, 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 J M, Hansen T, Le Paslier D, Linneberg A, Nielsen H B, 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, Doré J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J; MetaHIT Consortium, Bork P, Ehrlich SD, Wang J, Antolin M, Artiguenave F, Blottiere H, Borruel N, Bruls T, Casellas F, Chervaux C, Cultrone A, Delorme C, Denariaz G, Dervyn R, Forte M, Friss C, van de Guchte M, Guedon E, Haimet F, Jamet A, Juste C, Kaci G, Kleerebezem M, Knol J, Kristensen M, Layec S, Le Roux K, Leclerc M, Maguin E, Minardi RM, Oozeer R, Rescigno M, Sanchez N, Tims S, Torrejon T, Varela E, de Vos W, Winogradsky Y, Zoetendal E(2010).A human gut microbial gene catalogue established by metagenomic sequencing. Nature, 464(7285): 59–65

PMID

83 Ridaura V K, Faith J J, Rey F E, Cheng J, Duncan A E, Kau A L, Ggriffin N W, Lombard V, Henrissat B, Bain JR, Muehlbauer M J, Ilkaveya O, Semenkovich C F, Funai K, Hayashi D K, Lyle B J, Martini M C, Ursell L K, Clemente J C, Treuren W V, Walters W A, Knight R, Newgard C B, Heath AC & Gordon JI (2013). Cultured gut microbiota from twins discordant for obesity modulate adiposity and metabolic phenotypes in mice. Science, 341(6150): 1–22

PMID

84 Roberfroid M, Gibson G R, Hoyles L, McCartney A L, Rastall R, Rowland I, Wolvers D, Watzl B, Szajewska H, Stahl B, Guarner F, Respondek F, Whelan K, Coxam V, Davicco M J, Léotoing L, Wittrant Y, Delzenne N M, Cani P D, Neyrinck A M, Meheust A (2010). Prebiotic effects: metabolic and health benefits. Br J Nutr, 104(S2Suppl 2): S1–S63

PMID

85 Sartor R B (2008). Microbial influences in inflammatory bowel diseases. Gastroenterology, 134(2): 577–594

PMID

86 Savage D C (1977). Microbial ecology of the gastrointestinal tract. Annu Rev Microbiol, 31(1): 107–133

PMID

87 Scanlan P D, Shanahan F, O’Mahony C, Marchesi J R (2006). Culture-independent analyses of temporal variation of the dominant fecal microbiota and targeted bacterial subgroups in Crohn’s disease. J Clin Microbiol, 44(11): 3980–3988

PMID

88 Scott L J, Mohlke K L, Bonnycastle L L, Willer C J, Li Y, Duren W L, Erdos M R, Stringham H M, Chines P S, Jackson A U, Prokunina-Olsson L, Ding C J, Swift A J, Narisu N, Hu T, Pruim R, Xiao R, Li X Y, Conneely K N, Riebow N L, Sprau A G, Tong M, White P P, Hetrick K N, Barnhart M W, Bark C W, Goldstein J L, Watkins L, Xiang F, Saramies J, Buchanan T A, Watanabe R M, Valle T T, Kinnunen L, Abecasis G R, Pugh E W, Doheny K F, Bergman R N, Tuomilehto J, Collins F S, Boehnke M (2007). A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science, 316(5829): 1341–1345

PMID

89 Sharon I, Morowitz M J, Thomas B C, Costello E K, Relman D A, Banfield J F (2013). Time series community genomics analysis reveals rapid shifts in bacterial species, strains, and phage during infant gut colonization. Genome Res, 23(1): 111–120

PMID

90 Sheehan D, Shanahan F (2017). The Gut Microbiota in Inflammatory Bowel Disease. Gastroenterol Clin North Am, 46(1): 143–154

PMID

91 Slattery J, MacFabe D F, Frye R E (2016). The significance of the enteric microbiome on the development of childhood disease: A review of prebiotic and probiotic therapies in disorders of childhood. Clin Med Insights Pediatr, 10: CMPed.S38338–107

PMID

92 Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermúdez-Humarán L G, Gratadoux J J, Blugeon S, Bridonneau C, Furet J P, Corthier G, Grangette C, Vasquez N, Pochart P, Trugnan G, Thomas G, Blottière H M, Doré 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

PMID

93 Sokol H, Seksik P (2010). The intestinal microbiota in inflammatory bowel diseases: time to connect with the host. Curr Opin Gastroenterol, 26(4): 327–331

PMID

94 Tang W H W, Kitai T, Hazen S L (2017). Gut Microbiota in Cardiovascular Health and Disease. Circ Res, 120(7): 1183–1196

PMID

95 Tong M, Li X, Wegener Parfrey L, Roth B, Ippoliti A, Wei B, Borneman J, McGovern D P, Frank D N, Li E, Horvath S, Knight R, Braun J (2013). A modular organization of the human intestinal mucosal microbiota and its association with inflammatory bowel disease. PLoS One, 8(11): e80702

PMID

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

PMID

97 Turnbaugh P J, Ley R E, Mahowald M A, Magrini V, Mardis E R, Gordon J I (2006). An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, 444(7122): 1027– 1131

PMID

98 Tvede M, Rask-Madsen J (1989). Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients. Lancet, 333(8648): 1156–1160

PMID

99 Vrieze A, Van Nood E, Holleman F, Salojärvi J, Kootte R S, Bartelsman J F, Dallinga-Thie G M, Ackermans M T, Serlie M J, Oozeer R, Derrien M, Druesne A, Van Hylckama Vlieg J E, Bloks V W, Groen A K, Heilig H G, Zoetendal E G, Stroes E S, de Vos W M, Hoekstra J B, Nieuwdorp M (2012). Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology, 143(4): 913–6.

PMID

100 Walsh C J, Guinane C M, O’Toole P W, Cotter P D (2014). Beneficial modulation of the gut microbiota. FEBS Lett, 588(22): 4120–4130

PMID

101 Wolf K J, Lorenz R G (2012). Gut Microbiota and Obesity. Curr Obes Rep, 1(1): 1–8

PMID

102 Woodworth M H, Carpentieri C, Sitchenko K L, Kraft C S (2017). Challenges in fecal donor selection and screening for fecal microbiota transplantation: A review. Gut Microbes, 8(3): 225–237

PMID

103 Yadav H, Lee J H, Lloyd J, Walter P, Rane S G (2013). Beneficial metabolic effects of a probiotic via butyrate-induced GLP-1 hormone secretion. J Biol Chem, 288(35): 25088–97

PMID

104 Zhu W, Winter M G, Byndloss M X, Spiga L, Duerkop B A, Hughes E R, Büttner L, de Lima Romão E, Behrendt C L, Lopez C A, Sifuentes-Dominguez L, Huff-Hardy K, Wilson R P, Gillis C C, Tükel Ç, Koh A Y, Burstein E, Hooper L V, Bäumler A J, Winter S E (2018). Precision editing of the gut microbiota ameliorates colitis. Nature, 553(7687): 208–211

PMID