Antibiotics have significant and long-lasting effects on the intestinal microbiota and consequently reduce colonization resistance against pathogens, including By altering the community structure of the gut microbiome, antibiotics alter the intestinal metabolome, which includes both host- and microbe-derived metabolites. The mechanisms by which antibiotics reduce colonization resistance against are unknown yet important for development of preventative and therapeutic approaches against this pathogen. This review focuses on how antibiotics alter the structure of the gut microbiota and how this alters microbial metabolism in the intestine. Interactions between gut microbial products and spore germination, growth, and toxin production are discussed. New bacterial therapies to restore changes in bacteria-driven intestinal metabolism following antibiotics will have important applications for treatment and prevention of infection.


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Literature Cited

  1. Aldridge BB, Rhee KY. 1.  2014. Microbial metabolomics: innovation, application, insight. Curr. Opin. Microbiol. 19:90–96 [Google Scholar]
  2. Antharam VC, Li EC, Ishmael A, Sharma A, Mai V. 2.  et al. 2013. Intestinal dysbiosis and depletion of butyrogenic bacteria in Clostridium difficile infection and nosocomial diarrhea. J. Clin. Microbiol. 51:2884–92 [Google Scholar]
  3. Antonopoulos DA, Huse SM, Morrison HG, Schmidt TM, Sogin ML, Young VB. 3.  2009. Reproducible community dynamics of the gastrointestinal microbiota following antibiotic perturbation. Infect. Immun. 77:2367–75 [Google Scholar]
  4. Antunes LC, Han J, Ferreira RB, Lolic P, Borchers CH, Finlay BB. 4.  2011. The effect of antibiotic treatment on the intestinal metabolome. Antimicrob. Agents Chemother. 55: 1494:1503 [Google Scholar]
  5. Artis D. 5.  2008. Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. Nat. Rev. Immunol. 8:411–20 [Google Scholar]
  6. Bartlett JG. 6.  1984. Antibiotic-associated colitis. Dis. Mon. 30:1–54 [Google Scholar]
  7. Bartlett JG. 7.  1996. Management of Clostridium difficile infection and other antibiotic-associated diarrhoeas. Eur. J. Gastroenterol. Hepatol. 8:1054–61 [Google Scholar]
  8. Bartlett JG. 8.  2002. Clinical practice: antibiotic-associated diarrhea. N. Engl. J. Med. 346:334–39 [Google Scholar]
  9. Bartlett JG. 9.  2006. Narrative review: the new epidemic of Clostridium difficile-associated enteric disease. Ann. Intern. Med. 145:758–64 [Google Scholar]
  10. Bartlett JG, Chang TW, Gurwith M, Gorbach SL, Onderdonk AB. 10.  1978. Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia. N. Engl. J. Med. 298:531–34 [Google Scholar]
  11. Bartlett JG, Onderdonk AB, Cisneros RL, Kasper DL. 11.  2004. Commentary: Bartlett JG, Onderdonk AB, Cisneros RL, Kasper DL. Clindamycin-associated colitis due to a toxin-producing species of Clostridium in hamsters. J. Infect. Dis. 1977; 136:701 J. Infect. Dis. 190:202–9 [Google Scholar]
  12. Bassis CM, Theriot CM, Young VB. 12.  2014. Alteration of the murine gastrointestinal microbiota by tigecycline leads to increased susceptibility to Clostridium difficile infection. Antimicrob. Agents Chemother. 58:2767–74 [Google Scholar]
  13. Bassis CM, Young VB, Schmidt TM. 13.  2013. Methods for characterizing microbial communities associated with the human body. The Human Microbiota: How Microbial Communities Affect Health and Disease DN Fredricks 51–74 Hoboken, NJ: Wiley [Google Scholar]
  14. Beaugerie L, Petit JC. 14.  2004. Microbial-gut interactions in health and disease: antibiotic-associated diarrhoea. Best Pract. Res. Clin. Gastroenterol. 18:337–52 [Google Scholar]
  15. Bernstein H, Bernstein C, Payne CM, Dvorakova K, Garewal H. 15.  2005. Bile acids as carcinogens in human gastrointestinal cancers. Mutat. Res. 589:47–65 [Google Scholar]
  16. Best EL, Freeman J, Wilcox MH. 16.  2012. Models for the study of Clostridium difficile infection. Gut. Microbes 3:145–67 [Google Scholar]
  17. Bohnhoff M, Drake BL, Miller CP. 17.  1954. Effect of streptomycin on susceptibility of intestinal tract to experimental Salmonella infection. Proc. Soc. Exp. Biol. Med. 86:132–37 [Google Scholar]
  18. Bohnhoff M, Miller CP. 18.  1962. Enhanced susceptibility to Salmonella infection in streptomycin-treated mice. J. Infect. Dis. 111:117–27 [Google Scholar]
  19. Bouillaut L, Dubois T, Sonenshein AL, Dupuy B. 19.  2014. Integration of metabolism and virulence in Clostridium difficile. Res. Microbiol. 166:375–83 [Google Scholar]
  20. Bouillaut L, Self WT, Sonenshein AL. 20.  2013. Proline-dependent regulation of Clostridium difficile Stickland metabolism. J. Bacteriol. 195:844–54 [Google Scholar]
  21. Buffie CG, Bucci V, Stein RR, McKenney PT, Ling L. 21.  et al. 2014. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517:205–8 [Google Scholar]
  22. Buffie CG, Pamer EG. 22.  2013. Microbiota-mediated colonization resistance against intestinal pathogens. Nat. Rev. Immunol. 13:790–801 [Google Scholar]
  23. Canani RB, Costanzo MD, Leone L, Pedata M, Meli R, Calignano A. 23.  2011. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J. Gastroenterol. 17:1519–28 [Google Scholar]
  24. Carlson PE Jr, Walk ST, Bourgis AE, Liu MW, Kopliku F. 24.  et al. 2013. The relationship between phenotype, ribotype, and clinical disease in human Clostridium difficile isolates. Anaerobe 24:109–16 [Google Scholar]
  25. Chang JY, Antonopoulos DA, Kalra A, Tonelli A, Khalife WT. 25.  et al. 2008. Decreased diversity of the fecal microbiome in recurrent Clostridium difficile-associated diarrhea. J. Infect. Dis. 197:435–38 [Google Scholar]
  26. Chen X, Katchar K, Goldsmith JD, Nanthakumar N, Cheknis A. 26.  et al. 2008. A mouse model of Clostridium difficile-associated disease. Gastroenterology 135:1984–92 [Google Scholar]
  27. Chiang JY. 27.  2009. Bile acids: regulation of synthesis. J. Lipid Res. 50:1955–66 [Google Scholar]
  28. Corthier G, Dubos F, Raibaud P. 28.  1985. Modulation of cytotoxin production by Clostridium difficile in the intestinal tracts of gnotobiotic mice inoculated with various human intestinal bacteria. Appl. Environ. Microbiol. 49:250–52 [Google Scholar]
  29. Cummings JH, Macfarlane GT. 29.  1991. The control and consequences of bacterial fermentation in the human colon. J. Appl. Bacteriol. 70:443–59 [Google Scholar]
  30. Dai ZL, Wu G, Zhu WY. 30.  2011. Amino acid metabolism in intestinal bacteria: links between gut ecology and host health. Front. Biosci. 16:1768–86 [Google Scholar]
  31. Dethlefsen L, Relman DA. 31.  2011. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. PNAS 108:Suppl. 14554–61 [Google Scholar]
  32. Ding T, Schloss PD. 32.  2014. Dynamics and associations of microbial community types across the human body. Nature 509:357–60 [Google Scholar]
  33. Dubberke ER, Olsen MA. 33.  2012. Burden of Clostridium difficile on the healthcare system. Clin. Infect. Dis. 55:S88–92 [Google Scholar]
  34. Dupuy B, Sonenshein AL. 34.  1998. Regulated transcription of Clostridium difficile toxin genes. Mol. Microbiol. 27:107–20 [Google Scholar]
  35. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L. 35.  et al. 2005. Diversity of the human intestinal microbial flora. Science 308:1635–38 [Google Scholar]
  36. Fekety R, Silva J, Toshniwal R, Allo M, Armstrong J. 36.  et al. 1979. Antibiotic-associated colitis: effects of antibiotics on Clostridium difficile and the disease in hamsters. Rev. Infect. Dis. 1:386–97 [Google Scholar]
  37. Flint HJ, Scott KP, Duncan SH, Louis P, Forano E. 37.  2012. Microbial degradation of complex carbohydrates in the gut. Gut. Microbes 3:289–306 [Google Scholar]
  38. Frank DN, Pace NR. 38.  2008. Gastrointestinal microbiology enters the metagenomics era. Curr. Opin. Gastroenterol. 24:4–10 [Google Scholar]
  39. Frank DN, St. Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. 39.  2007. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. PNAS 104:13780–85 [Google Scholar]
  40. Freedberg DE, Salmasian H, Friedman C, Abrams JA. 40.  2013. Proton pump inhibitors and risk for recurrent Clostridium difficile infection among inpatients. Am. J. Gastroenterol. 108:1794–801 [Google Scholar]
  41. Freeman J, Wilcox MH. 41.  1999. Antibiotics and Clostridium difficile. Microbes Infect. 1:377–84 [Google Scholar]
  42. Freter R. 42.  1955. The fatal enteric cholera infection in the guinea pig, achieved by inhibition of normal enteric flora. J. Infect. Dis. 97:57–65 [Google Scholar]
  43. Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G. 43.  et al. 2013. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504:446–50 [Google Scholar]
  44. Giel JL, Sorg JA, Sonenshein AL, Zhu J. 44.  2010. Metabolism of bile salts in mice influences spore germination in Clostridium difficile. PLOS ONE 5:e8740 [Google Scholar]
  45. Gill SR, Pop M, Deboy RT, Eckburg PB, Turnbaugh PJ. 45.  et al. 2006. Metagenomic analysis of the human distal gut microbiome. Science 312:1355–59 [Google Scholar]
  46. Hall JC, O'Toole E. 46.  1935. Intestinal flora in new-born infants with a description of a new pathogenic anaerobe, Bacillus difficilis. Am. J. Dis. Child 49:390–402 [Google Scholar]
  47. Hamilton MJ, Weingarden AR, Unno T, Khoruts A, Sadowsky MJ. 47.  2013. High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria. Gut Microbes 4:125–35 [Google Scholar]
  48. Heeg D, Burns DA, Cartman ST, Minton NP. 48.  2012. Spores of Clostridium difficile clinical isolates display a diverse germination response to bile salts. PLOS ONE 7:e32381 [Google Scholar]
  49. Hogenauer C, Hammer HF, Krejs GJ, Reisinger EC. 49.  1998. Mechanisms and management of antibiotic-associated diarrhea. Clin. Infect. Dis. 27:702–10 [Google Scholar]
  50. Hove H, Tvede M, Mortensen PB. 50.  1996. Antibiotic-associated diarrhoea, Clostridium difficile, and short-chain fatty acids. Scand. J. Gastroenterol. 31:688–93 [Google Scholar]
  51. Hoverstad T, Carlstedt-Duke B, Lingaas E, Midtvedt T, Norin KE. 51.  et al. 1986. Influence of ampicillin, clindamycin, and metronidazole on faecal excretion of short-chain fatty acids in healthy subjects. Scand. J. Gastroenterol. 21:621–26 [Google Scholar]
  52. 52. Hum. Microbiome Proj. C 2012. A framework for human microbiome research. Nature 486:215–21 [Google Scholar]
  53. 53. Hum. Microbiome Proj. C 2012. Structure, function and diversity of the healthy human microbiome. Nature 486:207–14 [Google Scholar]
  54. Ikeda D, Karasawa T, Yamakawa K, Tanaka R, Namiki M, Nakamura S. 54.  1998. Effect of isoleucine on toxin production by Clostridium difficile in a defined medium. Zentralbl. Bakteriol. 287:375–86 [Google Scholar]
  55. Kamada N, Kim YG, Sham HP, Vallance BA, Puente JL. 55.  et al. 2012. Regulated virulence controls the ability of a pathogen to compete with the gut microbiota. Science 336:1325–29 [Google Scholar]
  56. Karasawa T, Ikoma S, Yamakawa K, Nakamura S. 56.  1995. A defined growth medium for Clostridium difficile. Microbiology 141:Part 2371–75 [Google Scholar]
  57. Karasawa T, Maegawa T, Nojiri T, Yamakawa K, Nakamura S. 57.  1997. Effect of arginine on toxin production by Clostridium difficile in defined medium. Microbiol. Immunol. 41:581–85 [Google Scholar]
  58. Karlsson S, Lindberg A, Norin E, Burman LG, Akerlund T. 58.  2000. Toxins, butyric acid, and other short-chain fatty acids are coordinately expressed and down-regulated by cysteine in Clostridium difficile. Infect. Immun. 68:5881–88 [Google Scholar]
  59. Kelly CP. 59.  2012. Current strategies for management of initial Clostridium difficile infection. J. Hosp. Med. 7:Suppl. 3S5–10 [Google Scholar]
  60. Kelly CP, LaMont JT. 60.  1998. Clostridium difficile infection. Annu. Rev. Med. 49:375–90 [Google Scholar]
  61. Kelly CP, LaMont JT. 61.  2008. Clostridium difficile—more difficult than ever. N. Engl. J. Med. 359:1932–40 [Google Scholar]
  62. Kinross J, Li JV, Muirhead LJ, Nicholson J. 62.  2014. Nutritional modulation of the metabonome: applications of metabolic phenotyping in translational nutritional research. Curr. Opin. Gastroenterol. 30:196–207 [Google Scholar]
  63. Kinross JM, Darzi AW, Nicholson JK. 63.  2011. Gut microbiome-host interactions in health and disease. Genome Med. 3:14 [Google Scholar]
  64. Knights D, Ward TL, McKinlay CE, Miller H, Gonzalez A. 64.  et al. 2014. Rethinking “enterotypes”. Cell Host Microbe 16:433–37 [Google Scholar]
  65. Koenigsknecht MJ, Theriot CM, Bergin IL, Schumacher CA, Schloss PD, Young VB. 65.  2014. Dynamics and establishment of Clostridium difficile infection in the murine gastrointestinal tract. Infect. Immun. 83:934–41 [Google Scholar]
  66. Koenigsknecht MJ, Young VB. 66.  2013. Faecal microbiota transplantation for the treatment of recurrent Clostridium difficile infection: current promise and future needs. Curr. Opin. Gastroenterol. 29:628–32 [Google Scholar]
  67. Larsbrink J, Rogers TE, Hemsworth GR, McKee LS, Tauzin AS. 67.  et al. 2014. A discrete genetic locus confers xyloglucan metabolism in select human gut Bacteroidetes. Nature 506:498–502 [Google Scholar]
  68. Lawley TD, Clare S, Walker AW, Stares MD, Connor TR. 68.  et al. 2012. Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice. PLOS Pathogens 8:e1002995 [Google Scholar]
  69. Lawley TD, Young VB. 69.  2013. Murine models to study Clostridium difficile infection and transmission. Anaerobe 24:94–97 [Google Scholar]
  70. Leatham MP, Banerjee S, Autieri SM, Mercado-Lubo R, Conway T, Cohen PS. 70.  2009. Precolonized human commensal Escherichia coli strains serve as a barrier to E. coli O157:H7 growth in the streptomycin-treated mouse intestine. Infect. Immun. 77:2876–86 [Google Scholar]
  71. Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK. 71.  et al. 2015. Burden of Clostridium difficile infection in the United States. N. Engl. J. Med. 372:825–34 [Google Scholar]
  72. Ley RE, Peterson DA, Gordon JI. 72.  2006. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124:837–48 [Google Scholar]
  73. Lupp C, Robertson ML, Wickham ME, Sekirov I, Champion OL. 73.  et al. 2007. Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae. Cell Host Microbe 2:119–29 [Google Scholar]
  74. Macfarlane GT, Macfarlane S. 74.  2012. Bacteria, colonic fermentation, and gastrointestinal health. J AOAC Int. 95:50–60 [Google Scholar]
  75. Mani N, Dupuy B. 75.  2001. Regulation of toxin synthesis in Clostridium difficile by an alternative RNA polymerase sigma factor. PNAS 98:5844–49 [Google Scholar]
  76. Matamouros S, England P, Dupuy B. 76.  2007. Clostridium difficile toxin expression is inhibited by the novel regulator TcdC. Mol. Microbiol. 64:1274–88 [Google Scholar]
  77. May T, Mackie RI, Fahey GC Jr, Cremin JC, Garleb KA. 77.  1994. Effect of fiber source on short-chain fatty acid production and on the growth and toxin production by Clostridium difficile. Scand. J. Gastroenterol. 29:916–22 [Google Scholar]
  78. McCollum DL, Rodriguez JM. 78.  2012. Detection, treatment, and prevention of Clostridium difficile infection. Clin. Gastroenterol. Hepatol. 10:581–92 [Google Scholar]
  79. McDonald LC, Killgore GE, Thompson A, Owens RC Jr, Kazakova SV. 79.  et al. 2005. An epidemic, toxin gene-variant strain of Clostridium difficile. N. Engl. J. Med. 353:2433–41 [Google Scholar]
  80. McFarland LV. 80.  2008. Antibiotic-associated diarrhea: epidemiology, trends and treatment. Future Microbiol. 3:563–78 [Google Scholar]
  81. McFee RB, Abdelsayed GG. 81.  2009. Clostridium difficile. Dis. Mon. 55:439–70 [Google Scholar]
  82. Merrigan M, Venugopal A, Mallozzi M, Roxas B, Viswanathan VK. 82.  et al. 2010. Human hypervirulent Clostridium difficile strains exhibit increased sporulation as well as robust toxin production. J. Bacteriol. 192:4904–11 [Google Scholar]
  83. Midtvedt T. 83.  1974. Microbial bile acid transformation. Am. J. Clin. Nutr. 27:1341–47 [Google Scholar]
  84. Moeller AH, Peeters M, Ayouba A, Ngole EM, Esteban A. 84.  et al. 2015. Stability of the gorilla microbiome despite simian immunodeficiency virus infection. Mol. Ecol. 24:690–97 [Google Scholar]
  85. Moore WE, Holdeman LV. 85.  1974. Human fecal flora: the normal flora of 20 Japanese-Hawaiians. Appl. Microbiol. 27:961–79 [Google Scholar]
  86. Nagaro KJ, Phillips ST, Cheknis AK, Sambol SP, Zukowski WE. 86.  et al. 2013. Nontoxigenic Clostridium difficile protects hamsters against challenge with historic and epidemic strains of toxigenic BI/NAP1/027 C. difficile. Antimicrob. Agents Chemother. 57:5266–70 [Google Scholar]
  87. Nakamura S, Nakashio S, Yamakawa K, Tanabe N, Nishida S. 87.  1982. Carbohydrate fermentation by Clostridium difficile. Microbiol. Immunol. 26:107–11 [Google Scholar]
  88. Ng KM, Ferreyra JA, Higginbottom SK, Lynch JB, Kashyap PC. 88.  et al. 2013. Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature 502:96–99 [Google Scholar]
  89. Onderdonk AB, Cisneros RL, Bartlett JG. 89.  1980. Clostridium difficile in gnotobiotic mice. Infect. Immun. 28:277–82 [Google Scholar]
  90. Owens RC Jr, Donskey CJ, Gaynes RP, Loo VG, Muto CA. 90.  2008. Antimicrobial-associated risk factors for Clostridium difficile infection. Clin. Infect. Dis. 46:Suppl. 1S19–31 [Google Scholar]
  91. Pepin J, Saheb N, Coulombe MA, Alary ME, Corriveau MP. 91.  et al. 2005. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec. Clin. Infect. Dis. 41:1254–60 [Google Scholar]
  92. Peterfreund GL, Vandivier LE, Sinha R, Marozsan AJ, Olson WC. 92.  et al. 2012. Succession in the gut microbiome following antibiotic and antibody therapies for Clostridium difficile. PLOS ONE 7:e46966 [Google Scholar]
  93. Proctor LM. 93.  2011. The Human Microbiome Project in 2011 and beyond. Cell Host Microbe 10:287–91 [Google Scholar]
  94. Rea MC, Sit CS, Clayton E, O'Connor PM, Whittal RM. 94.  et al. 2010. Thuricin CD, a posttranslationally modified bacteriocin with a narrow spectrum of activity against Clostridium difficile. PNAS 107:9352–57 [Google Scholar]
  95. Reeves AE, Koenigsknecht MJ, Bergin IL, Young VB. 95.  2012. Suppression of Clostridium difficile in the gastrointestinal tracts of germfree mice inoculated with a murine isolate from the family Lachnospiraceae. Infect. Immun. 80:3786–94 [Google Scholar]
  96. Reeves AE, Theriot CM, Bergin IL, Huffnagle GB, Schloss PD, Young VB. 96.  2011. The interplay between microbiome dynamics and pathogen dynamics in a murine model of Clostridium difficile infection. Gut Microbes 2:145–58 [Google Scholar]
  97. Ridlon JM, Kang D-J, Hylemon PB. 97.  2006. Bile salt biotransformations by human intestinal bacteria. J. Lipid Res. 47:241–59 [Google Scholar]
  98. Robinson CD, Auchtung JM, Collins J, Britton RA. 98.  2014. Epidemic Clostridium difficile strains demonstrate increased competitive fitness compared to nonepidemic isolates. Infect. Immun. 82:2815–25 [Google Scholar]
  99. Rolfe RD. 99.  1984. Role of volatile fatty acids in colonization resistance to Clostridium difficile. Infect. Immun. 45:185–91 [Google Scholar]
  100. Romick-Rosendale LE, Goodpaster AM, Hanwright PJ, Patel NB, Wheeler ET. 100.  et al. 2009. NMR-based metabonomics analysis of mouse urine and fecal extracts following oral treatment with the broad-spectrum antibiotic enrofloxacin (Baytril). Magn. Reson. Chem. 47:Suppl. 1S36–46 [Google Scholar]
  101. Savage DC. 101.  1977. Microbial ecology of the gastrointestinal tract. Annu. Rev. Microbiol. 31:107–33 [Google Scholar]
  102. Scaria J, Chen JW, Useh N, He H, McDonough SP. 102.  et al. 2014. Comparative nutritional and chemical phenome of Clostridium difficile isolates determined using phenotype microarrays. Int. J. Infect. Dis. 27:20–25 [Google Scholar]
  103. Schubert AM, Rogers MA, Ring C, Mogle J, Petrosino JP. 103.  et al. 2014. Microbiome data distinguish patients with Clostridium difficile infection and non-C. difficile-associated diarrhea from healthy controls. mBio 5:e01021–14 [Google Scholar]
  104. Seekatz AM, Aas J, Gessert CE, Rubin TA, Saman DM. 104.  et al. 2014. Recovery of the gut microbiome following fecal microbiota transplantation. mBio 5:e00893–14 [Google Scholar]
  105. Silvester KR, Englyst HN, Cummings JH. 105.  1995. Ileal recovery of starch from whole diets containing resistant starch measured in vitro and fermentation of ileal effluent. Am. J. Clin. Nutr. 62:403–11 [Google Scholar]
  106. Smith DG, Robinson HJ. 106.  1945. The influence of streptomycin and streptothricin on the intestinal flora of mice. J. Bacteriol. 50:613–21 [Google Scholar]
  107. Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA. 107.  et al. 2013. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341:569–73 [Google Scholar]
  108. Sonnenburg JL, Xu J, Leip DD, Chen CH, Westover BP. 108.  et al. 2005. Glycan foraging in vivo by an intestine-adapted bacterial symbiont. Science 307:1955–59 [Google Scholar]
  109. Sorg JA. 109.  2014. Microbial bile acid metabolic clusters: the bouncers at the bar. Cell Host Microbe 16:551–52 [Google Scholar]
  110. Sorg JA, Sonenshein AL. 110.  2008. bile salts and glycine as cogerminants for Clostridium difficile spores. J. Bacteriol. 190:2505–12 [Google Scholar]
  111. Sorg JA, Sonenshein AL. 111.  2009. Chenodeoxycholate is an inhibitor of Clostridium difficile spore germination. J. Bacteriol. 191:1115–17 [Google Scholar]
  112. Sorg JA, Sonenshein AL. 112.  2010. Inhibiting the initiation of Clostridium difficile spore germination using analogs of chenodeoxycholic acid, a bile acid. J. Bacteriol. 192:4983–90 [Google Scholar]
  113. Sridharan GV, Choi K, Klemashevich C, Wu C, Prabakaran D. 113.  et al. 2014. Prediction and quantification of bioactive microbiota metabolites in the mouse gut. Nat. Commun. 5:5492 [Google Scholar]
  114. Stabler RA, He M, Dawson L, Martin M, Valiente E. 114.  et al. 2009. Comparative genome and phenotypic analysis of Clostridium difficile 027 strains provides insight into the evolution of a hypervirulent bacterium. Genome Biol. 10:R102 [Google Scholar]
  115. Stanley JD, Bartlett JG, Dart BW IV, Ashcraft JH. 115.  2013. Clostridium difficile infection. Curr. Probl. Surg. 50:302–37 [Google Scholar]
  116. Stecher B, Macpherson AJ, Hapfelmeier S, Kremer M, Stallmach T, Hardt WD. 116.  2005. Comparison of Salmonella enterica serovar Typhimurium colitis in germfree mice and mice pretreated with streptomycin. Infect. Immun. 73:3228–41 [Google Scholar]
  117. Swann JR, Want EJ, Geier FM, Spagou K, Wilson ID. 117.  et al. 2011. Systemic gut microbial modulation of bile acid metabolism in host tissue compartments. PNAS 108:Suppl. 14523–30 [Google Scholar]
  118. Tedesco FJ, Barton RW, Alpers DH. 118.  1974. Clindamycin-associated colitis: a prospective study. Ann. Intern. Med. 81:429–33 [Google Scholar]
  119. Theriot CM, Koenigsknecht MJ, Carlson PE Jr, Hatton GE, Nelson AM. 119.  et al. 2014. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. Nat. Commun. 5:3114 [Google Scholar]
  120. Tremaroli V, Backhed F. 120.  2012. Functional interactions between the gut microbiota and host metabolism. Nature 489:242–49 [Google Scholar]
  121. van der Waaij D, Berghuis-de Vries JM, Lekkerkerk L-van der Wees. 121.  1971. Colonization resistance of the digestive tract in conventional and antibiotic-treated mice. J. Hyg. 69:405–11 [Google Scholar]
  122. Van Houte J, Gibbons RJ. 122.  1966. Studies of the cultivable flora of normal human feces. Antonie Van Leeuwenhoek 32:212–22 [Google Scholar]
  123. van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG. 123.  et al. 2013. Duodenal infusion of donor feces for recurrent Clostridium difficile. N. Engl. J. Med. 368:407–15 [Google Scholar]
  124. Vollaard EJ, Clasener HA. 124.  1994. Colonization resistance. Antimicrob. Agents Chemother. 38:409–14 [Google Scholar]
  125. Voth DE, Ballard JD. 125.  2005. Clostridium difficile toxins: mechanism of action and role in disease. Clin. Microbiol. Rev. 18:247–63 [Google Scholar]
  126. Vrieze A, Out C, Fuentes S, Jonker L, Reuling I. 126.  et al. 2014. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity. J. Hepatol. 60:824–31 [Google Scholar]
  127. Warny M, Pepin J, Fang A, Killgore G, Thompson A. 127.  et al. 2005. Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet 366:1079–84 [Google Scholar]
  128. Weingarden AR, Chen C, Bobr A, Yao D, Lu Y. 128.  et al. 2014. Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection. Am. J. Physiol. Gastrointest. Liver Physiol. 306:G310–19 [Google Scholar]
  129. Wells JE, Hylemon PB. 129.  2000. Identification and characterization of a bile acid 7α-dehydroxylation operon in Clostridium sp. strain TO-931, a highly active 7α-dehydroxylating strain isolated from human feces. Appl. Environ. Microbiol. 66:1107–13 [Google Scholar]
  130. Wensinck F, Ruseler-van Embden JG. 130.  1971. The intestinal flora of colonization-resistant mice. J. Hyg. 69:413–21 [Google Scholar]
  131. Wilson KH. 131.  1993. The microecology of Clostridium difficile. Clin. Infect. Dis. 16:Suppl. 4S214–18 [Google Scholar]
  132. Wilson KH, Kennedy MJ, Fekety FR. 132.  1982. Use of sodium taurocholate to enhance spore recovery on a medium selective for Clostridium difficile. J. Clin. Microbiol. 15:443–46 [Google Scholar]
  133. Wilson KH, Perini F. 133.  1988. Role of competition for nutrients in suppression of Clostridium difficile by the colonic microflora. Infect. Immun. 56:2610–14 [Google Scholar]
  134. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY. 134.  et al. 2011. Linking long-term dietary patterns with gut microbial enterotypes. Science 334:105–8 [Google Scholar]
  135. Yap IK, Li JV, Saric J, Martin FP, Davies H. 135.  et al. 2008. Metabonomic and microbiological analysis of the dynamic effect of vancomycin-induced gut microbiota modification in the mouse. J. Proteome Res. 7:3718–28 [Google Scholar]
  136. Young VB, Schmidt TM. 136.  2004. Antibiotic-associated diarrhea accompanied by large-scale alterations in the composition of the fecal microbiota. J. Clin. Microbiol. 42:1203–6 [Google Scholar]
  137. Young VB, Schmidt TM. 137.  2008. Overview of the gastrointestinal microbiota. Adv. Exp. Med. Biol. 635:29–40 [Google Scholar]
  138. Zhao Y, Wu J, Li JV, Zhou NY, Tang H, Wang Y. 138.  2013. Gut microbiota composition modifies fecal metabolic profiles in mice. J. Proteome Res. 12:2987–99 [Google Scholar]
  139. Zheng X, Xie G, Zhao A, Zhao L, Yao C. 139.  et al. 2011. The footprints of gut microbial-mammalian co-metabolism. J. Proteome Res. 10:5512–22 [Google Scholar]

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