Advertisement

The Promise of Personalized Medicine

  • Matthew L. Stoll
Chapter

Abstract

There is substantial potential for the human intestinal microbiota to be mined for its therapeutic potential. Absent exogenous perturbations, the intestinal microbiota tends to be highly stable throughout adult life, and it appears to be associated with a variety of rheumatic diseases. Furthermore, the microbiota can influence the metabolism of many medicines used to treat inflammatory diseases, thus potentially playing a role in the disease process even in the absence of specific abnormalities in its composition. We have multiple tools at hand to alter the microbiota, and the future may hold targeted approaches to remove specific bacteria associated with a particular condition. Finally, there is evidence that an individual’s baseline microbiota might predict his or her response to dietary therapy, thus ushering in an era of individualized medicine targeting the human intestinal microbiota.

Keywords

Microbiota Autoimmune diseases Probiotics Fecal microbial transplant Individualized medicine 

List of Abbreviations

AID

Anti-inflammatory diet

CGR

Cardiac glycoside reductase

EEN

Exclusive enteral nutrition

FMT

Fecal microbial transplantation

HMP

Human Microbiome Project

IBD

Inflammatory bowel disease

JIA

Juvenile idiopathic arthritis

RA

Rheumatoid arthritis

ReA

Reactive arthritis

SCFA

Short-chain fatty acids

SpA

Spondyloarthritis

References

  1. 1.
    Clunie GP, Lennard L. Relevance of thiopurine methyltransferase status in rheumatology patients receiving azathioprine. Rheumatology (Oxford). 2004;43(1):13–8.CrossRefGoogle Scholar
  2. 2.
    Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59–65.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Brewerton DA, Hart FD, Nicholls A, Caffrey M, James DC, Sturrock RD. Ankylosing spondylitis and HL-A 27. Lancet. 1973;1(7809):904–7.CrossRefPubMedGoogle Scholar
  4. 4.
    Backhed F, Roswall J, Peng Y, Feng Q, Jia H, Kovatcheva-Datchary P, et al. Dynamics and stabilization of the human gut Microbiome during the first year of life. Cell Host Microbe. 2015;17(6):852.CrossRefPubMedGoogle Scholar
  5. 5.
    Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A. 2010;107(26):11971–5.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486(7402):222–7.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Hollister EB, Riehle K, Luna RA, Weidler EM, Rubio-Gonzales M, Mistretta TA, et al. Structure and function of the healthy pre-adolescent pediatric gut microbiome. Microbiome. 2015;3:36.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Costello EK, Lauber CL, Hamady M, Fierer N, Gordon JI, Knight R. Bacterial community variation in human body habitats across space and time. Science. 2009;326(5960):1694–7.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Faith JJ, Guruge JL, Charbonneau M, Subramanian S, Seedorf H, Goodman AL, et al. The long-term stability of the human gut microbiota. Science. 2013;341(6141):1237439.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Franzosa EA, Huang K, Meadow JF, Gevers D, Lemon KP, Bohannan BJ, et al. Identifying personal microbiomes using metagenomic codes. Proc Natl Acad Sci U S A. 2015;112(22):E2930–8.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Taurog JD, Richardson JA, Croft JT, Simmons WA, Zhou M, Fernandez-Sueiro JL, et al. The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med. 1994;180(6):2359–64.CrossRefPubMedGoogle Scholar
  12. 12.
    Wu HJ, Ivanov II, Darce J, Hattori K, Shima T, Umesaki Y, et al. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity. 2010;32(6):815–27.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Berer K, Mues M, Koutrolos M, Rasbi ZA, Boziki M, Johner C, et al. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature. 2011;479(7374):538–41.CrossRefPubMedGoogle Scholar
  14. 14.
    Vieira AT, Macia L, Galvao I, Martins FS, Canesso MC, Amaral FA, et al. A role for gut Microbiota and the metabolite-sensing receptor GPR43 in a murine model of gout. Arthritis Rheumatol. 2015;67(6):1646–56.CrossRefPubMedGoogle Scholar
  15. 15.
    Sokol H, Seksik P, Furet JP, Firmesse O, Nion-Larmurier I, Beaugerie L, et al. Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis. 2009;15(8):1183–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Machiels K, Joossens M, Sabino J, De Preter V, Arijs I, Eeckhaut V, et al. A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut. 2013;63(8):1275–83.CrossRefPubMedGoogle Scholar
  17. 17.
    Stoll ML, Kumar R, Morrow CD, Lefkowitz EJ, Cui X, Genin A, et al. Altered microbiota associated with abnormal humoral immune responses to commensal organisms in enthesitis-related arthritis. Arthritis Res Ther. 2014;16(6):486.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Shaw KA, Bertha M, Hofmekler T, Chopra P, Vatanen T, Srivatsa A, et al. Dysbiosis, inflammation, and response to treatment: a longitudinal study of pediatric subjects with newly diagnosed inflammatory bowel disease. Genome Med. 2016;8(1):75.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Maeda Y, Kurakawa T, Umemoto E, Motooka D, Ito Y, Gotoh K, et al. Dysbiosis contributes to arthritis development via activation of autoreactive T cells in the intestine. Arthritis Rheumatol. 2016;68(11):2646–61.CrossRefPubMedGoogle Scholar
  20. 20.
    Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife. 2013;2:e01202.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Tejesvi MV, Arvonen M, Kangas SM, Keskitalo PL, Pirttila AM, Karttunen TJ, et al. Faecal microbiome in new-onset juvenile idiopathic arthritis. Eur J Clin Microbiol Infect Dis. 2015;35(3):363–70.CrossRefPubMedGoogle Scholar
  22. 22.
    Giongo A, Gano KA, Crabb DB, Mukherjee N, Novelo LL, Casella G, et al. Toward defining the autoimmune microbiome for type 1 diabetes. ISME J. 2011;5(1):82–91.CrossRefPubMedGoogle Scholar
  23. 23.
    Murri M, Leiva I, Gomez-Zumaquero JM, Tinahones FJ, Cardona F, Soriguer F, et al. Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study. BMC Med. 2013;11:46.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Zhou Y, Zhi F. Lower level of Bacteroides in the gut Microbiota is associated with inflammatory bowel disease: a meta-analysis. Biomed Res Int. 2016;2016:5828959.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Durban A, Abellan JJ, Jimenez-Hernandez N, Salgado P, Ponce M, Ponce J, et al. Structural alterations of faecal and mucosa-associated bacterial communities in irritable bowel syndrome. Environ Microbiol Rep. 2012;4(2):242–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Scher JU, Ubeda C, Artacho A, Attur M, Isaac S, Reddy SM, et al. Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. Arthritis Rheumatol. 2015;67(1):128–39.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Michail S, Durbin M, Turner D, Griffiths AM, Mack DR, Hyams J, et al. Alterations in the gut microbiome of children with severe ulcerative colitis. Inflamm Bowel Dis. 2012;18(10):1799–808.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Taur Y, Jenq RR, Perales MA, Littmann ER, Morjaria S, Ling L, et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood. 2014;124(7):1174–82.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Stoll ML. Gut microbes, immunity, and spondyloarthritis. Clin Immunol. 2015;159(2):134–42.CrossRefPubMedGoogle Scholar
  30. 30.
    Thaiss CA, Zmora N, Levy M, Elinav E. The microbiome and innate immunity. Nature. 2016;535(7610):65–74.CrossRefGoogle Scholar
  31. 31.
    Round JL, Lee SM, Li J, Tran G, Jabri B, Chatila TA, et al. The toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science. 2011;332(6032):974–7.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Farkas AM, Panea C, Goto Y, Nakato G, Galan-Diez M, Narushima S, et al. Induction of Th17 cells by segmented filamentous bacteria in the murine intestine. J Immunol Methods. 2015;421:104–11.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Hussaarts L, Yazdanbakhsh M, Guigas B. Priming dendritic cells for th2 polarization: lessons learned from helminths and implications for metabolic disorders. Front Immunol. 2014;5:499.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Summers RW, Elliott DE, Urban JF Jr, Thompson R, Weinstock JV. Trichuris suis therapy in Crohn’s disease. Gut. 2005;54(1):87–90.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Summers RW, Elliott DE, Urban JF Jr, Thompson RA, Weinstock JV. Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology. 2005;128(4):825–32.CrossRefPubMedGoogle Scholar
  36. 36.
    Spanogiannopoulos P, Bess EN, Carmody RN, Turnbaugh PJ. The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism. Nat Rev Microbiol. 2016;14(5):273–87.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Jourova L, Anzenbacher P, Anzenbacherova E. Human gut microbiota plays a role in the metabolism of drugs. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016;160(3):317–26.CrossRefPubMedGoogle Scholar
  38. 38.
    Morgan SL, Baggott JE, Vaughn WH, Austin JS, Veitch TA, Lee JY, et al. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial. Ann Intern Med. 1994;121(11):833–41.CrossRefPubMedGoogle Scholar
  39. 39.
    Graham LD, Myones BL, Rivas-Chacon RF, Pachman LM. Morbidity associated with long-term methotrexate therapy in juvenile rheumatoid arthritis. J Pediatr. 1992;120(3):468–73.CrossRefPubMedGoogle Scholar
  40. 40.
    Nayak RR, O’Loughlin C, Fischbach M, Turnbaugh PJ. Methotrexate is an antibacterial drug metabolized by human gut Bacteria [abstract]. Arthritis Rheum. 2016;68(suppl 10).Google Scholar
  41. 41.
    Robertson LW, Chandrasekaran A, Reuning RH, Hui J, Rawal BD. Reduction of digoxin to 20R-dihydrodigoxin by cultures of Eubacterium lentum. Appl Environ Microbiol. 1986;51(6):1300–3.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Greenblatt DJ, Smith TW, Koch-Weser J. Bioavailability of drugs: the digoxin dilemma. Clin Pharmacokinet. 1976;1(1):36–51.CrossRefPubMedGoogle Scholar
  43. 43.
    Lindenbaum J, Rund DG, Butler VP Jr, Tse-Eng D, Saha JR. Inactivation of digoxin by the gut flora: reversal by antibiotic therapy. N Engl J Med. 1981;305(14):789–94.CrossRefPubMedGoogle Scholar
  44. 44.
    Saha JR, Butler VP Jr, Neu HC, Lindenbaum J. Digoxin-inactivating bacteria: identification in human gut flora. Science. 1983;220(4594):325–7.CrossRefPubMedGoogle Scholar
  45. 45.
    Haiser HJ, Gootenberg DB, Chatman K, Sirasani G, Balskus EP, Turnbaugh PJ. Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta. Science. 2013;341(6143):295–8.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Sokol H. Probiotics and antibiotics in IBD. Dig Dis. 2014;32(Suppl 1):10–7.CrossRefPubMedGoogle Scholar
  47. 47.
    Carter JD. Reactive arthritis: defined etiologies, emerging pathophysiology, and unresolved treatment. Infect Dis Clin N Am. 2006;20(4):827–47.CrossRefGoogle Scholar
  48. 48.
    Barber CE, Kim J, Inman RD, Esdaile JM, James MT. Antibiotics for treatment of reactive arthritis: a systematic review and metaanalysis. J Rheumatol. 2013;40(6):916–28.CrossRefPubMedGoogle Scholar
  49. 49.
    Smieja M, MacPherson DW, Kean W, Schmuck ML, Goldsmith CH, Buchanan W, et al. Randomised, blinded, placebo controlled trial of doxycycline for chronic seronegative arthritis. Ann Rheum Dis. 2001;60(12):1088–94.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Derikx LA, Dieleman LA, Hoentjen F. Probiotics and prebiotics in ulcerative colitis. Best Pract Res Clin Gastroenterol. 2016;30(1):55–71.CrossRefPubMedGoogle Scholar
  51. 51.
    Jenks K, Stebbings S, Burton J, Schultz M, Herbison P, Highton J. Probiotic therapy for the treatment of spondyloarthritis: a randomized controlled trial. J Rheumatol. 2010;37(10):2118–25.CrossRefPubMedGoogle Scholar
  52. 52.
    Brophy S, Burrows CL, Brooks C, Gravenor MB, Siebert S, Allen SJ. Internet-based randomised controlled trials for the evaluation of complementary and alternative medicines: probiotics in spondyloarthropathy. BMC Musculoskelet Disord. 2008;9:4.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Shukla A, Gaur P, Aggarwal A. Effect of probiotics on clinical and immune parameters in enthesitis-related arthritis category of juvenile idiopathic arthritis. Clin Exp Immunol. 2016;185(3):301–8.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Kristensen NB, Bryrup T, Allin KH, Nielsen T, Hansen TH, Pedersen O. Alterations in fecal microbiota composition by probiotic supplementation in healthy adults: a systematic review of randomized controlled trials. Genome Med. 2016;8(1):52.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Shen TC, Albenberg L, Bittinger K, Chehoud C, Chen YY, Judge CA, et al. Engineering the gut microbiota to treat hyperammonemia. J Clin Invest. 2015;125(7):2841–50.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334(6052):105–8.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559–63.CrossRefGoogle Scholar
  58. 58.
    Bindels LB, Neyrinck AM, Salazar N, Taminiau B, Druart C, Muccioli GG, et al. Non digestible oligosaccharides modulate the gut Microbiota to control the development of Leukemia and associated Cachexia in mice. PLoS One. 2015;10(6):e0131009.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Lukens JR, Gurung P, Vogel P, Johnson GR, Carter RA, McGoldrick DJ, et al. Dietary modulation of the microbiome affects autoinflammatory disease. Nature. 2014;516(7530):246–9.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    McAllan L, Skuse P, Cotter PD, O’Connor P, Cryan JF, Ross RP, et al. Protein quality and the protein to carbohydrate ratio within a high fat diet influences energy balance and the gut microbiota in C57BL/6J mice. PLoS One. 2014;9(2):e88904.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Le Leu RK, Young GP, Hu Y, Winter J, Conlon MA, et al. Dig Dis Sci. 2013;58(12):3475–82.CrossRefPubMedGoogle Scholar
  62. 62.
    Sprong RC, Schonewille AJ, van der Meer R. Dietary cheese whey protein protects rats against mild dextran sulfate sodium-induced colitis: role of mucin and microbiota. J Dairy Sci. 2010;93(4):1364–71.CrossRefPubMedGoogle Scholar
  63. 63.
    Kakodkar S, Farooqui AJ, Mikolaitis SL, Mutlu EA. The specific carbohydrate diet for inflammatory bowel disease: a case series. J Acad Nutr Diet. 2015;115(8):1226–32.CrossRefPubMedGoogle Scholar
  64. 64.
    Ruemmele FM. Role of diet in inflammatory bowel disease. Ann Nutr Metab. 2016;68(Suppl 1):33–41.CrossRefPubMedGoogle Scholar
  65. 65.
    Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, de Roos P, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504(7480):451–5.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Cao Y, Shen J, Ran ZH. Association between Faecalibacterium prausnitzii reduction and inflammatory bowel disease: a meta-analysis and systematic review of the literature. Gastroenterol Res Pract. 2014;2014:872725.PubMedPubMedCentralGoogle Scholar
  67. 67.
    Brotherton CS, Taylor AG, Bourguignon C, Anderson JG. A high-fiber diet may improve bowel function and health-related quality of life in patients with Crohn disease. Gastroenterol Nurs. 2014;37(3):206–16.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Olendzki BC, Silverstein TD, Persuitte GM, Ma Y, Baldwin KR, Cave D. An anti-inflammatory diet as treatment for inflammatory bowel disease: a case series report. Nutr J. 2014;13:5.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Sigall-Boneh R, Pfeffer-Gik T, Segal I, Zangen T, Boaz M, Levine A. Partial enteral nutrition with a Crohn’s disease exclusion diet is effective for induction of remission in children and young adults with Crohn’s disease. Inflamm Bowel Dis. 2014;20(8):1353–60.CrossRefPubMedGoogle Scholar
  70. 70.
    Whitten KE, Rogers P, Ooi CY, Day AS. International survey of enteral nutrition protocols used in children with Crohn’s disease. J Dig Dis. 2012;13(2):107–12.CrossRefPubMedGoogle Scholar
  71. 71.
    Heuschkel RB, Menache CC, Megerian JT, Baird AE. Enteral nutrition and corticosteroids in the treatment of acute Crohn’s disease in children. J Pediatr Gastroenterol Nutr. 2000;31(1):8–15.CrossRefPubMedGoogle Scholar
  72. 72.
    Berntson L, Hedlund-Treutiger I, Alving K. Anti-inflammatory effect of exclusive enteral nutrition in patients with juvenile idiopathic arthritis. Clin Exp Rheumatol. 2016;34(5):941–5.PubMedPubMedCentralGoogle Scholar
  73. 73.
    Berntson L, Agback P, Dicksved J. Changes in fecal microbiota and metabolomics in a child with juvenile idiopathic arthritis (JIA) responding to two treatment periods with exclusive enteral nutrition (EEN). Clin Rheumatol. 2016;35(6):1501–6.CrossRefPubMedGoogle Scholar
  74. 74.
    Kang C, Zhang Y, Zhu X, Liu K, Wang X, Chen M, et al. Healthy subjects differentially respond to dietary capsaicin correlating with the specific gut enterotypes. J Clin Endocrinol Metab. 2016;101(12):4681–9. jc20162786.CrossRefPubMedGoogle Scholar
  75. 75.
    Stapel SO, Asero R, Ballmer-Weber BK, Knol EF, Strobel S, Vieths S, et al. Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI task force report. Allergy. 2008;63(7):793–6.CrossRefPubMedGoogle Scholar
  76. 76.
    Shivappa N, Steck SE, Hurley TG, Hussey JR, Hebert JR. Designing and developing a literature-derived, population-based dietary inflammatory index. Public Health Nutr. 2014;17(8):1689–96.CrossRefPubMedGoogle Scholar
  77. 77.
    Russell GH, Kaplan JL, Youngster I, Baril-Dore M, Schindelar L, Hohmann E, et al. Fecal transplant for recurrent Clostridium difficile infection in children with and without inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2014;58(5):588–92.CrossRefPubMedGoogle Scholar
  78. 78.
    Zhang FM, Wang HG, Wang M, Cui BT, Fan ZN, Ji GZ. Fecal microbiota transplantation for severe enterocolonic fistulizing Crohn’s disease. World J Gastroenterol. 2013;19(41):7213–6.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Suskind DL, Brittnacher MJ, Wahbeh G, Shaffer ML, Hayden HS, Qin X, et al. Fecal microbial transplant effect on clinical outcomes and fecal microbiome in active Crohn’s disease. Inflamm Bowel Dis. 2015;21(3):556–63.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Suskind DL, Singh N, Nielson H, Wahbeh G. Fecal microbial transplant via nasogastric tube for active pediatric ulcerative colitis. J Pediatr Gastroenterol Nutr. 2015;60(1):27–9.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Quera R, Espinoza R, Estay C, Rivera D. Bacteremia as an adverse event of fecal microbiota transplantation in a patient with Crohn’s disease and recurrent Clostridium difficile infection. J Crohns Colitis. 2014;8(3):252–3.CrossRefPubMedGoogle Scholar
  82. 82.
    Kuntz TM, Gilbert JA. Introducing the Microbiome into precision medicine. Trends Pharmacol Sci. 2016;38(1):81–91.CrossRefPubMedGoogle Scholar
  83. 83.
    Guo L, McLean JS, Yang Y, Eckert R, Kaplan CW, Kyme P, et al. Precision-guided antimicrobial peptide as a targeted modulator of human microbial ecology. Proc Natl Acad Sci USA. 2015;112(24):7569–74.CrossRefGoogle Scholar
  84. 84.
    Kutter E, De Vos D, Gvasalia G, Alavidze Z, Gogokhia L, Kuhl S, et al. Phage therapy in clinical practice: treatment of human infections. Curr Pharm Biotechnol. 2010;11(1):69–86.CrossRefPubMedGoogle Scholar
  85. 85.
    Stoll ML, Kumar R, Lefkowitz EJ, Cron RQ, Morrow CD, Barnes S. Fecal metabolomics in pediatric spondyloarthritis implicate decreased metabolic diversity and altered tryptophan metabolism as pathogenic factors. Genes Immun. 2016;17(7):400–5.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pediatrics, Division of RheumatologyUniversity of Alabama at BirminghamBirminghamUSA

Personalised recommendations