Control of Infection by Defined Microbial Communities.

James Collins, Jennifer M Auchtung
Author Information
  1. James Collins: Alkek Center for Metagenomics and Microbiome Research and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030.
  2. Jennifer M Auchtung: Alkek Center for Metagenomics and Microbiome Research and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030.

Abstract

Each year in the United States, billions of dollars are spent combating almost half a million infections (CDIs) and trying to reduce the ∼29,000 patient deaths in which has an attributed role. In Europe, disease prevalence varies by country and level of surveillance, though yearly costs are estimated at €3 billion. One factor contributing to the significant health care burden of is the relatively high frequency of recurrent CDIs. Recurrent CDI, i.e., a second episode of symptomatic CDI occurring within 8 weeks of successful initial CDI treatment, occurs in ∼25% of patients, with 35 to 65% of these patients experiencing multiple episodes of recurrent disease. Using microbial communities to treat recurrent CDI, either as whole fecal transplants or as defined consortia of bacterial isolates, has shown great success (in the case of fecal transplants) or potential promise (in the case of defined consortia of isolates). This review will briefly summarize the epidemiology and physiology of infection, describe our current understanding of how fecal microbiota transplants treat recurrent CDI, and outline potential ways that knowledge can be used to rationally design and test alternative microbe-based therapeutics.

References

  1. Gut Microbes. 2013 Mar-Apr;4(2):125-35 [PMID: 23333862]
  2. J Hosp Infect. 2016 Jul;93(3):286-9 [PMID: 27209056]
  3. JAMA. 2015 Jan 27;313(4):398-408 [PMID: 25626036]
  4. Science. 2013 Sep 6;341(6150):1241214 [PMID: 24009397]
  5. Clin Infect Dis. 1994 Feb;18(2):181-7 [PMID: 8161624]
  6. JAMA. 2014 Nov 5;312(17):1772-8 [PMID: 25322359]
  7. Eur J Pediatr. 1993 Apr;152(4):319-22 [PMID: 8482281]
  8. Annu Rev Microbiol. 2011;65:501-21 [PMID: 21682645]
  9. Proc Natl Acad Sci U S A. 2010 May 18;107(20):9352-7 [PMID: 20435915]
  10. J Pediatr Gastroenterol Nutr. 2010 Jul;51(1):2-7 [PMID: 20512057]
  11. J Bacteriol. 2010 Oct;192(19):4983-90 [PMID: 20675492]
  12. Nature. 2012 Jun 13;486(7402):207-14 [PMID: 22699609]
  13. Clin Infect Dis. 2011 Nov;53(10):1003-6 [PMID: 21976462]
  14. Infect Immun. 2015 Oct;83(10):3838-46 [PMID: 26169276]
  15. Infect Immun. 1988 Oct;56(10):2610-4 [PMID: 3417352]
  16. Open Forum Infect Dis. 2015 Feb 04;2(1):ofv004 [PMID: 26034755]
  17. Lancet. 1998 Feb 28;351(9103):633-6 [PMID: 9500319]
  18. J Clin Microbiol. 2003 Jul;41(7):3413-4 [PMID: 12843107]
  19. Dig Dis Sci. 1979 Jul;24(7):545-50 [PMID: 456241]
  20. Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):18674-9 [PMID: 24167244]
  21. Transpl Infect Dis. 2012 Dec;14(6):E161-5 [PMID: 23121625]
  22. Antimicrob Agents Chemother. 2013 May;57(5):2326-32 [PMID: 23478961]
  23. Clin Infect Dis. 2012 Oct;55(8):1056-63 [PMID: 22784871]
  24. Antimicrob Agents Chemother. 2013 Nov;57(11):5266-70 [PMID: 23939887]
  25. Am J Gastroenterol. 2013 Apr;108(4):500-8 [PMID: 23511459]
  26. Inflamm Bowel Dis. 2016 Jul;22(7):1744-54 [PMID: 27120571]
  27. J Immunol Res. 2014;2014:462740 [PMID: 24995345]
  28. Int J Antimicrob Agents. 2016 Jul;48(1):1-10 [PMID: 27216385]
  29. Surgery. 1958 Nov;44(5):854-9 [PMID: 13592638]
  30. Clin Infect Dis. 2014 Feb;58(4):541-5 [PMID: 24368622]
  31. J Clin Microbiol. 1983 Oct;18(4):1017-9 [PMID: 6630458]
  32. Toxins (Basel). 2016 May 14;8(5): [PMID: 27187475]
  33. PLoS One. 2016 Aug 16;11(8):e0161174 [PMID: 27529553]
  34. J Clin Microbiol. 2000 Jun;38(6):2386-8 [PMID: 10835010]
  35. Front Cell Infect Microbiol. 2012 Mar 16;2:28 [PMID: 22919620]
  36. Minn Med. 2009 Jul;92(7):38-40 [PMID: 19708314]
  37. J Clin Microbiol. 2011 Dec;49(12):4040-6 [PMID: 21956985]
  38. Int Microbiol. 2005 Mar;8(1):43-8 [PMID: 15906260]
  39. Med Lett Drugs Ther. 2011 Sep 19;53(1373):73-4 [PMID: 21921871]
  40. Anaerobe. 2016 Feb;37:13-24 [PMID: 26596863]
  41. J Bacteriol. 2009 Feb;191(3):1115-7 [PMID: 19060152]
  42. J Infect Dis. 2013 Sep;208(6):917-20 [PMID: 23776194]
  43. J Clin Gastroenterol. 2017 Feb;51(2):145-150 [PMID: 26974758]
  44. Microbiome. 2013 Jan 09;1(1):3 [PMID: 24467987]
  45. Nat Commun. 2013;4:2601 [PMID: 24131955]
  46. Gastroenterology. 2015 Jul;149(1):223-37 [PMID: 25982290]
  47. N Engl J Med. 2000 Feb 10;342(6):390-7 [PMID: 10666429]
  48. J Bacteriol. 2008 Apr;190(7):2505-12 [PMID: 18245298]
  49. JAMA. 2016 Jan 12;315(2):142-9 [PMID: 26757463]
  50. Anaerobe. 2016 Aug;40:54-7 [PMID: 27180007]
  51. J Lipid Res. 2006 Feb;47(2):241-59 [PMID: 16299351]
  52. PLoS One. 2016 Mar 24;11(3):e0151964 [PMID: 27011211]
  53. PLoS Biol. 2008 Nov 18;6(11):e280 [PMID: 19018661]
  54. N Engl J Med. 2005 Dec 8;353(23):2442-9 [PMID: 16322602]
  55. Am J Gastroenterol. 2012 Nov;107(11):1755; author reply p.1755-6 [PMID: 23160295]
  56. Clin Infect Dis. 2012 Aug;55 Suppl 2:S132-42 [PMID: 22752862]
  57. Infect Immun. 2014 Jul;82(7):2815-25 [PMID: 24733099]
  58. Clin Gastroenterol Hepatol. 2014 Feb;12(2):283-8 [PMID: 24107393]
  59. Gut Liver. 2015 Mar;9(2):247-50 [PMID: 25721003]
  60. J Med Microbiol. 2008 Jun;57(Pt 6):717-724 [PMID: 18480328]
  61. Toxicol Appl Pharmacol. 2014 Jun 1;277(2):138-45 [PMID: 24657338]
  62. J Infect Dis. 1977 Nov;136(5):701-5 [PMID: 915343]
  63. Anaerobe. 2015 Aug;34:1-7 [PMID: 25817005]
  64. Nat Rev Microbiol. 2012 Nov;10(11):735-42 [PMID: 23000955]
  65. N Engl J Med. 2011 Feb 3;364(5):422-31 [PMID: 21288078]
  66. Infect Immun. 2013 Oct;81(10):3757-69 [PMID: 23897605]
  67. Clin Infect Dis. 2016 Mar 1;62(5):596-602 [PMID: 26565008]
  68. Lancet. 2005 Sep 24-30;366(9491):1079-84 [PMID: 16182895]
  69. J Biol Chem. 2005 Jun 3;280(22):21237-45 [PMID: 15767259]
  70. J Infect. 2013 Feb;66(2):115-28 [PMID: 23103666]
  71. Infect Immun. 1984 Jul;45(1):185-91 [PMID: 6735467]
  72. J Immunol. 2012 Sep 15;189(6):3085-91 [PMID: 22888139]
  73. Immunology. 2016 Jan;147(1):114-24 [PMID: 26455347]
  74. Int J Infect Dis. 2014 Oct;27:20-5 [PMID: 25130165]
  75. Anaerobe. 2016 Oct;41:68-78 [PMID: 27108093]
  76. J Bacteriol. 2010 Oct;192(19):4904-11 [PMID: 20675495]
  77. Infect Control Hosp Epidemiol. 2010 Jan;31(1):21-7 [PMID: 19929371]
  78. ISME J. 2014 Aug;8(8):1621-33 [PMID: 24577353]
  79. Infect Immun. 2012 Aug;80(8):2704-11 [PMID: 22615253]
  80. Circ Res. 1973 Oct;33(4):393-402 [PMID: 4741941]
  81. J Gerontol A Biol Sci Med Sci. 2016 Jul;71(7):916-22 [PMID: 26809495]
  82. Gastroenterology. 2017 Jun;152(8):1817-1819 [PMID: 28461190]
  83. Ann Intern Med. 2008 Apr 15;148(8):632-3 [PMID: 18413636]
  84. Lancet. 1983 Oct 8;2(8354):845 [PMID: 6137662]
  85. Arch Intern Med. 2012 Jan 23;172(2):191-3 [PMID: 22271132]
  86. Nat Commun. 2014 Apr 15;5:3654 [PMID: 24736369]
  87. Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4639-44 [PMID: 20616009]
  88. Nature. 2016 Jul 06;535(7610):85-93 [PMID: 27383983]
  89. Clin Infect Dis. 2012 Aug;55 Suppl 2:S104-9 [PMID: 22752857]
  90. J Infect. 2009 Jun;58(6):403-10 [PMID: 19394704]
  91. Lancet. 1989 May 27;1(8648):1156-60 [PMID: 2566734]
  92. Clin Infect Dis. 2014 Sep 15;59(6):858-61 [PMID: 24917658]
  93. Infect Immun. 2015 Mar;83(3):934-41 [PMID: 25534943]
  94. Gut Microbes. 2014 Jan-Feb;5(1):15-27 [PMID: 24253566]
  95. J Hosp Infect. 1998 Feb;38(2):93-100 [PMID: 9522287]
  96. Clin Infect Dis. 2015 Jul 15;61(2):233-41 [PMID: 25828993]
  97. CMAJ. 2005 Oct 25;173(9):1037-42 [PMID: 16179431]
  98. Nat Microbiol. 2016 Jul 11;1(8):16108 [PMID: 27573114]
  99. mSphere. 2016 Jan 06;1(1): [PMID: 27239562]
  100. Cell Host Microbe. 2015 Jun 10;17(6):852 [PMID: 26308884]
  101. Infect Control Hosp Epidemiol. 2015 Nov;36(11):1318-23 [PMID: 26288985]
  102. J Pharm Pract. 2013 Oct;26(5):464-75 [PMID: 24064435]
  103. Clin Gastroenterol Hepatol. 2010 May;8(5):471-3 [PMID: 20117243]
  104. J Med Microbiol. 2008 Jun;57(Pt 6):784-789 [PMID: 18480338]
  105. Am J Physiol. 1999 Feb;276(2):G485-90 [PMID: 9950823]
  106. Microbiome. 2016 Mar 14;4:12 [PMID: 26975510]
  107. Anaerobe. 2015 Jun;33:105-8 [PMID: 25769665]
  108. Clin Infect Dis. 2012 Nov;55(9):1209-15 [PMID: 22843784]
  109. Scand J Gastroenterol. 2013 Mar;48(3):266-73 [PMID: 23163886]
  110. Am J Gastroenterol. 2012 May;107(5):761-7 [PMID: 22290405]
  111. N Engl J Med. 2013 Jan 31;368(5):407-15 [PMID: 23323867]
  112. J Infect Dis. 2016 Jul 15;214(2):173-81 [PMID: 26908752]
  113. Science. 2012 Jun 8;336(6086):1268-73 [PMID: 22674334]
  114. Gastroenterology. 2008 Feb;134(2):577-94 [PMID: 18242222]
  115. Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4578-85 [PMID: 20668239]
  116. Nat Genet. 2013 Jan;45(1):109-13 [PMID: 23222960]
  117. Nature. 2012 Aug 9;488(7410):178-84 [PMID: 22797518]
  118. Can J Infect Dis Med Microbiol. 2016;2016:8207418 [PMID: 27366181]
  119. Clin Infect Dis. 2013 Jun;56(11):1589-600 [PMID: 23463640]
  120. Aliment Pharmacol Ther. 2016 Jun;43(11):1142-53 [PMID: 27086647]
  121. J Bacteriol. 2011 Jan;193(1):274-82 [PMID: 20971909]
  122. Microbiome. 2017 May 4;5(1):50 [PMID: 28473000]
  123. Am J Gastroenterol. 2002 Jul;97(7):1769-75 [PMID: 12135033]
  124. Pediatr Infect Dis J. 2014 Nov;33(11):1198-200 [PMID: 24853539]
  125. J Antimicrob Chemother. 2014 Apr;69(4):881-91 [PMID: 24324224]
  126. J Bacteriol. 2015 Dec 14;198(5):777-86 [PMID: 26668265]
  127. Ther Adv Infect Dis. 2013 Feb;1(1):19-35 [PMID: 25165542]
  128. PLoS One. 2010 Jan 15;5(1):e8740 [PMID: 20090901]
  129. J Clin Gastroenterol. 2016 May-Jun;50(5):403-7 [PMID: 26352106]
  130. J Gastroenterol. 2017 Apr;52(4):452-465 [PMID: 27329502]
  131. Am J Gastroenterol. 2013 Aug;108(8):1367 [PMID: 23912408]
  132. Infect Dis Ther. 2016 Sep;5(3):231-51 [PMID: 27370914]
  133. Am J Gastroenterol. 2012 Jul;107(7):1001-10 [PMID: 22710578]
  134. Clin Infect Dis. 2012 Dec;55(12):1661-8 [PMID: 22972866]
  135. PLoS Biol. 2016 Jul 12;14(7):e1002503 [PMID: 27404502]
  136. Clin Microbiol Infect. 2014 Nov;20(11):1112-8 [PMID: 25273480]
  137. Nat Commun. 2014;5:3114 [PMID: 24445449]
  138. Cell Microbiol. 2015 Dec;17(12):1752-65 [PMID: 26445410]
  139. J Clin Microbiol. 2004 Mar;42(3):1203-6 [PMID: 15004076]
  140. J Antimicrob Chemother. 2013 Sep;68(9):1951-61 [PMID: 23620467]
  141. Lancet. 1978 Apr 15;1(8068):802-3 [PMID: 85818]
  142. J Clin Gastroenterol. 2012 Feb;46(2):145-9 [PMID: 22157239]
  143. PLoS One. 2015 Feb 23;10(2):e0117195 [PMID: 25707002]
  144. BMC Infect Dis. 2015 Nov 14;15:516 [PMID: 26573915]
  145. Infect Control Hosp Epidemiol. 2010 May;31(5):431-55 [PMID: 20307191]
  146. Gut Microbes. 2014;5(6):696-710 [PMID: 25564777]
  147. J Pediatr Gastroenterol Nutr. 2000 Sep;31(3):220-31 [PMID: 10997362]
  148. Nature. 2015 Jan 8;517(7533):205-8 [PMID: 25337874]
  149. Scand J Gastroenterol. 1994 Oct;29(10):916-22 [PMID: 7839098]
  150. Lancet. 1978 May 20;1(8073):1063-6 [PMID: 77366]
  151. J Infect Dis. 2008 Feb 1;197(3):435-8 [PMID: 18199029]
  152. Microbiome. 2014 Nov 25;2:42 [PMID: 25426290]
  153. Nutrients. 2016 Apr 06;8(4):202 [PMID: 27058556]
  154. N Engl J Med. 2005 Dec 8;353(23):2433-41 [PMID: 16322603]
  155. Infect Dis Ther. 2016 Sep;5(3):207-30 [PMID: 27470257]
  156. J Med Microbiol. 2001 Aug;50(8):720-727 [PMID: 11478676]
  157. Infection. 2016 Oct;44(5):599-606 [PMID: 27062378]
  158. Anaerobe. 2016 Oct;41:51-57 [PMID: 27180657]
  159. Scand J Gastroenterol. 1986 Jun;21(5):621-6 [PMID: 3749800]
  160. Br Med J. 1978 Mar 18;1(6114):695 [PMID: 630301]
  161. Antimicrob Agents Chemother. 2011 Apr;55(4):1494-503 [PMID: 21282433]
  162. Emerg Microbes Infect. 2013 Sep;2(9):e62 [PMID: 26038491]
  163. J Lipid Res. 2009 Dec;50(12):2340-57 [PMID: 19498215]
  164. JAMA. 2015 May 5;313(17):1719-27 [PMID: 25942722]
  165. Clin Infect Dis. 2003 Mar 1;36(5):580-5 [PMID: 12594638]
  166. J Clin Gastroenterol. 2004 Jul;38(6):475-83 [PMID: 15220681]
  167. Anaerobe. 2013 Dec;24:109-16 [PMID: 23608205]
  168. J Clin Microbiol. 2013 Jun;51(6):1938-41 [PMID: 23554188]
  169. Antimicrob Agents Chemother. 2007 Aug;51(8):2883-7 [PMID: 17562803]
  170. J Infect Dis. 1982 Dec;146(6):727-33 [PMID: 7142747]
  171. N Engl J Med. 2015 Feb 26;372(9):825-34 [PMID: 25714160]
  172. J Clin Microbiol. 2012 Dec;50(12):4078-82 [PMID: 23052318]
  173. Nature. 2013 Oct 3;502(7469):96-9 [PMID: 23995682]

Grants

  1. R21 AI121522/NIAID NIH HHS
  2. R33 AI121522/NIAID NIH HHS
  3. U01 AI124290/NIAID NIH HHS

MeSH Term

Animals
Clostridioides difficile
Clostridium Infections
Fecal Microbiota Transplantation
Feces
Gastrointestinal Microbiome
Humans

Word Cloud

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