Interactions between the Gastrointestinal Microbiome and Clostridium difficile

Annual Review of Microbiology

Volumn 69, Issue 1, 2015, Pages 445-461

  Theriot, Casey M ^a   Young, Vincent B ^b  

^a NORTH CAROLINA STATE UNIVERSITY   (United States)

^b UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

Antibiotics; Bacterial metabolism; Bile acids; Clostridium difficile; Colonization resistance; Gut microbiota

Indexed keywords

AMINO ACID; ANTIBIOTIC AGENT; BACTERIAL TOXIN; CARBOHYDRATE; ANTIINFECTIVE AGENT;

ANTIBIOTIC ASSOCIATED DIARRHEA; BACTERIAL GROWTH; BACTERIAL METABOLISM; BILE ACID METABOLISM; CLOSTRIDIUM DIFFICILE INFECTION; HUMAN; INTESTINE FLORA; MICROBIAL COMMUNITY; MICROBIAL METABOLISM; MICROBIOME; PEPTOCLOSTRIDIUM DIFFICILE; PRIORITY JOURNAL; REVIEW; SPORE GERMINATION; ANIMAL; CLOSTRIDIUM INFECTION; DRUG EFFECTS; FERMENTATION; IMMUNE EVASION; METABOLISM; MICROBIOLOGY; MICROFLORA; ORGANISMAL INTERACTION;

ANIMALS; ANTI-BACTERIAL AGENTS; CLOSTRIDIUM DIFFICILE; CLOSTRIDIUM INFECTIONS; FERMENTATION; GASTROINTESTINAL MICROBIOME; HUMANS; IMMUNE EVASION; MICROBIAL INTERACTIONS; MICROBIOTA;

EID: 84945295917     PISSN: 00664227     EISSN: 15453251     Source Type: Book Series    
DOI: 10.1146/annurev-micro-091014-104115     Document Type: Review

References (139)

1. Aldridge BB, Rhee KY. 2014. Microbial metabolomics: innovation, application, insight. Curr. Opin. Microbiol. 19: 90-96
2. Antharam VC, Li EC, Ishmael A, Sharma A, Mai V, et al. 2013. Intestinal dysbiosis and depletion of butyrogenic bacteria in Clostridium difficile infection and nosocomial diarrhea. J. Clin. Microbiol. 51: 2884-92
3. Antonopoulos DA, Huse SM, Morrison HG, Schmidt TM, Sogin ML, Young VB. 2009. Reproducible community dynamics of the gastrointestinal microbiota following antibiotic perturbation. Infect. Immun. 77: 2367-75
4. Antunes LC, Han J, Ferreira RB, Lolic P, Borchers CH, Finlay BB. 2011. The effect of antibiotic treatment on the intestinal metabolome. Antimicrob. Agents Chemother. 55: 1494: 1503
5. ArtisD. 2008. Epithelial-cell recognition of commensal bacteria andmaintenance of immunehomeostasis in the gut. Nat. Rev. Immunol. 8: 411-20
6. Bartlett JG. 1984. Antibiotic-associated colitis. Dis. Mon. 30: 1-54
7. Bartlett JG. 1996. Management of Clostridium difficile infection and other antibiotic-associated diarrhoeas. Eur. J. Gastroenterol. Hepatol. 8: 1054-61
8. Bartlett JG. 2002. Clinical practice: Antibiotic-associated diarrhea. N. Engl. J. Med. 346: 334-39
9. Bartlett JG. 2006. Narrative review: The new epidemic of Clostridium difficile-associated enteric disease. Ann. Intern. Med. 145: 758-64
10. Bartlett JG, Chang TW, Gurwith M, Gorbach SL, Onderdonk AB. 1978. Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia. N. Engl. J. Med. 298: 531-34
11. Bartlett JG, Onderdonk AB, Cisneros RL, Kasper DL. 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
12. Bassis CM, Theriot CM, Young VB. 2014. Alteration of the murine gastrointestinal microbiota by tigecycline leads to increased susceptibility to Clostridium difficile infection. Antimicrob. Agents Chemother. 58: 2767-74
13. BassisCM, YoungVB, SchmidtTM. 2013. Methods for characterizingmicrobial communities associated with the human body. In The Human Microbiota: How Microbial Communities Affect Health and Disease, ed. DN Fredricks, pp. 51-74. Hoboken, NJ: Wiley
14. Beaugerie L, Petit JC. 2004. Microbial-gut interactions in health and disease: Antibiotic-associated diarrhoea. Best Pract. Res. Clin. Gastroenterol. 18: 337-52
15. Bernstein H, Bernstein C, Payne CM, Dvorakova K, Garewal H. 2005. Bile acids as carcinogens in human gastrointestinal cancers. Mutat. Res. 589: 47-65
16. Best EL, Freeman J, Wilcox MH. 2012. Models for the study of Clostridium difficile infection. Gut. Microbes 3: 145-67
17. Bohnhoff M, Drake BL, Miller CP. 1954. Effect of streptomycin on susceptibility of intestinal tract to experimental Salmonella infection. Proc. Soc. Exp. Biol. Med. 86: 132-37
18. Bohnhoff M, Miller CP. 1962. Enhanced susceptibility to Salmonella infection in streptomycin-treated mice. J. Infect. Dis. 111: 117-27
19. Bouillaut L, Dubois T, Sonenshein AL, Dupuy B. 2014. Integration of metabolism and virulence in Clostridium difficile. Res. Microbiol. 166: 375-83
20. Bouillaut L, Self WT, Sonenshein AL. 2013. Proline-dependent regulation of Clostridium difficile Stickland metabolism. J. Bacteriol. 195: 844-54
21. Buffie CG, Bucci V, Stein RR, McKenney PT, Ling L, et al. 2014. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517: 205-8
22. Buffie CG, Pamer EG. 2013. Microbiota-mediated colonization resistance against intestinal pathogens. Nat. Rev. Immunol. 13: 790-801
23. Canani RB, Costanzo MD, Leone L, Pedata M, Meli R, Calignano A. 2011. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J. Gastroenterol. 17: 1519-28
24. Carlson PE Jr, Walk ST, Bourgis AE, Liu MW, Kopliku F, et al. 2013. The relationship between phenotype, ribotype, and clinical disease in human Clostridium difficile isolates. Anaerobe 24: 109-16
25. Chang JY, Antonopoulos DA, Kalra A, Tonelli A, Khalife WT, et al. 2008. Decreased diversity of the fecal microbiome in recurrent Clostridium difficile-associated diarrhea. J. Infect. Dis. 197: 435-38
26. Chen X, KatcharK, Goldsmith JD, NanthakumarN, Cheknis A, et al. 2008. Amousemodel of Clostridium difficile-associated disease. Gastroenterology 135: 1984-92
27. Chiang JY. 2009. Bile acids: regulation of synthesis. J. Lipid Res. 50: 1955-66
28. Corthier G, Dubos F, Raibaud P. 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
29. Cummings JH, Macfarlane GT. 1991. The control and consequences of bacterial fermentation in the human colon. J. Appl. Bacteriol. 70: 443-59
30. Dai ZL, Wu G, ZhuWY. 2011. Amino acid metabolism in intestinal bacteria: links between gut ecology and host health. Front. Biosci. 16: 1768-86
31. Dethlefsen L, Relman DA. 2011. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. PNAS 108(Suppl. 1): 4554-61
32. Ding T, Schloss PD. 2014. Dynamics and associations of microbial community types across the human body. Nature 509: 357-60
33. Dubberke ER, OlsenMA. 2012. Burden of Clostridium difficile on the healthcare system. Clin. Infect. Dis. 55: S88-92
34. Dupuy B, Sonenshein AL. 1998. Regulated transcription of Clostridium difficile toxin genes. Mol. Microbiol. 27: 107-20
35. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, et al. 2005. Diversity of the human intestinal microbial flora. Science 308: 1635-38
36. Fekety R, Silva J, Toshniwal R, Allo M, Armstrong J, et al. 1979. Antibiotic-associated colitis: effects of antibiotics on Clostridium difficile and the disease in hamsters. Rev. Infect. Dis. 1: 386-97
37. Flint HJ, Scott KP, Duncan SH, Louis P, Forano E. 2012. Microbial degradation of complex carbohydrates in the gut. Gut. Microbes 3: 289-306
38. Frank DN, Pace NR. 2008. Gastrointestinal microbiology enters the metagenomics era. Curr. Opin. Gastroenterol. 24: 4-10
39. Frank DN, St. Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. 2007. Molecularphylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. PNAS 104: 13780-85
40. Freedberg DE, Salmasian H, Friedman C, Abrams JA. 2013. Proton pump inhibitors and risk for recurrent Clostridium difficile infection among inpatients. Am. J. Gastroenterol. 108: 1794-801
41. Freeman J, Wilcox MH. 1999. Antibiotics and Clostridium difficile. Microbes Infect. 1: 377-84
42. Freter R. 1955. The fatal enteric cholera infection in the guinea pig, achieved by inhibition of normal enteric flora. J. Infect. Dis. 97: 57-65
43. Furusawa Y, Obata Y, Fukuda S, Endo TA, NakatoG, et al. 2013. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504: 446-50
44. Giel JL, Sorg JA, Sonenshein AL, Zhu J. 2010. Metabolism of bile salts in mice influences spore germination in Clostridium difficile. PLOS ONE 5: e8740
45. Gill SR, Pop M, Deboy RT, Eckburg PB, Turnbaugh PJ, et al. 2006. Metagenomic analysis of the human distal gut microbiome. Science 312: 1355-59
46. Hall JC, O'Toole E. 1935. Intestinal flora in new-born infants with a description of a new pathogenic anaerobe, Bacillus difficilis. Am. J. Dis. Child 49: 390-402
47. Hamilton MJ, Weingarden AR, Unno T, Khoruts A, Sadowsky MJ. 2013. High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria. Gut Microbes 4: 125-35
48. Heeg D, Burns DA, Cartman ST, Minton NP. 2012. Spores of Clostridium difficile clinical isolates display a diverse germination response to bile salts. PLOS ONE 7: e32381
49. Hogenauer C, HammerHF, Krejs GJ, Reisinger EC. 1998. Mechanisms and management of antibioticassociated diarrhea. Clin. Infect. Dis. 27: 702-10
50. Hove H, TvedeM, Mortensen PB. 1996. Antibiotic-associated diarrhoea, Clostridium difficile, and shortchain fatty acids. Scand. J. Gastroenterol. 31: 688-93
51. Hoverstad T, Carlstedt-Duke B, Lingaas E, Midtvedt T, Norin KE, 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
52. Hum. Microbiome Proj. C. 2012. A framework for human microbiome research. Nature 486: 215-21
53. Hum. Microbiome Proj. C. 2012. Structure, function and diversity of the healthy human microbiome. Nature 486: 207-14
54. Ikeda D, Karasawa T, Yamakawa K, Tanaka R, Namiki M, Nakamura S. 1998. Effect of isoleucine on toxin production by Clostridium difficile in a defined medium. Zentralbl. Bakteriol. 287: 375-86
55. Kamada N, Kim YG, Sham HP, Vallance BA, Puente JL, et al. 2012. Regulated virulence controls the ability of a pathogen to compete with the gut microbiota. Science 336: 1325-29
56. Karasawa T, Ikoma S, YamakawaK, Nakamura S. 1995. A defined growthmedium for Clostridium difficile. Microbiology 141(Part 2): 371-75
57. Karasawa T, Maegawa T, Nojiri T, Yamakawa K, Nakamura S. 1997. Effect of arginine on toxin production by Clostridium difficile in defined medium. Microbiol. Immunol. 41: 581-85
58. Karlsson S, Lindberg A, Norin E, Burman LG, Akerlund T. 2000. Toxins, butyric acid, and other shortchain fatty acids are coordinately expressed and down-regulated by cysteine in Clostridium difficile. Infect. Immun. 68: 5881-88
59. Kelly CP. 2012. Current strategies for management of initial Clostridium difficile infection. J. Hosp. Med. 7(Suppl. 3): S5-10
60. Kelly CP, LaMont JT. 1998. Clostridium difficile infection. Annu. Rev. Med. 49: 375-90
61. Kelly CP, LaMont JT. 2008. Clostridium difficile-more difficult than ever. N. Engl. J. Med. 359: 1932-40
62. Kinross J, Li JV, Muirhead LJ, Nicholson J. 2014. Nutritional modulation of the metabonome: Applications ofmetabolic phenotyping in translational nutritional research. Curr. Opin. Gastroenterol. 30: 196-207
63. Kinross JM, Darzi AW, Nicholson JK. 2011. Gut microbiome-host interactions in health and disease. Genome Med. 3: 14
64. Knights D, Ward TL, McKinlay CE, Miller H, Gonzalez A, et al. 2014. Rethinking "enterotypes". Cell Host Microbe 16: 433-37
65. Koenigsknecht MJ, Theriot CM, Bergin IL, Schumacher CA, Schloss PD, Young VB. 2014. Dynamics and establishment of Clostridium difficile infection in the murine gastrointestinal tract. Infect. Immun. 83: 934-41
66. Koenigsknecht MJ, Young VB. 2013. Faecal microbiota transplantation for the treatment of recurrent Clostridium difficile infection: current promise and future needs. Curr. Opin. Gastroenterol. 29: 628-32
67. Larsbrink J, Rogers TE, Hemsworth GR, McKee LS, Tauzin AS, et al. 2014. A discrete genetic locus confers xyloglucan metabolism in select human gut Bacteroidetes. Nature 506: 498-502
68. Lawley TD, Clare S, Walker AW, Stares MD, Connor TR, 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
69. Lawley TD, Young VB. 2013. Murine models to study Clostridium difficile infection and transmission. Anaerobe 24: 94-97
70. Leatham MP, Banerjee S, Autieri SM, Mercado-Lubo R, Conway T, Cohen PS. 2009. Precolonized human commensal Escherichia coli strains serve as a barrier to E. Coli O157: H7 growth in the streptomycintreated mouse intestine. Infect. Immun. 77: 2876-86
71. Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, et al. 2015. Burden of Clostridium difficile infection in the United States. N. Engl. J. Med. 372: 825-34
72. Ley RE, Peterson DA, Gordon JI. 2006. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124: 837-48
73. Lupp C, Robertson ML, Wickham ME, Sekirov I, Champion OL, et al. 2007. Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae. Cell Host Microbe 2: 119-29
74. MacfarlaneGT, Macfarlane S. 2012. Bacteria, colonic fermentation, and gastrointestinal health. JAOAC Int. 95: 50-60
75. Mani N, Dupuy B. 2001. Regulation of toxin synthesis in Clostridium difficile by an alternative RNA polymerase sigma factor. PNAS 98: 5844-49
76. Matamouros S, England P, Dupuy B. 2007. Clostridium difficile toxin expression is inhibited by the novel regulator TcdC. Mol. Microbiol. 64: 1274-88
77. MayT, Mackie RI, FaheyGCJr, Cremin JC, Garleb KA. 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
78. McCollum DL, Rodriguez JM. 2012. Detection, treatment, and prevention of Clostridium difficile infection. Clin. Gastroenterol. Hepatol. 10: 581-92
79. McDonald LC, Killgore GE, Thompson A, Owens RC Jr, Kazakova SV, et al. 2005. An epidemic, toxin gene-variant strain of Clostridium difficile. N. Engl. J. Med. 353: 2433-41
80. McFarland LV. 2008. Antibiotic-associated diarrhea: epidemiology, trends and treatment. Future Microbiol. 3: 563-78
81. McFee RB, Abdelsayed GG. 2009. Clostridium difficile. Dis. Mon. 55: 439-70
82. Merrigan M, Venugopal A, Mallozzi M, Roxas B, Viswanathan VK, et al. 2010. Human hypervirulent Clostridium difficile strains exhibit increased sporulation as well as robust toxin production. J. Bacteriol. 192: 4904-11
83. Midtvedt T. 1974. Microbial bile acid transformation. Am. J. Clin. Nutr. 27: 1341-47
84. Moeller AH, PeetersM, Ayouba A, Ngole EM, Esteban A, et al. 2015. Stability of the gorilla microbiome despite simian immunodeficiency virus infection. Mol. Ecol. 24: 690-97
85. MooreWE, Holdeman LV. 1974. Human fecal flora: The normal flora of 20 Japanese-Hawaiians. Appl. Microbiol. 27: 961-79
86. Nagaro KJ, Phillips ST, Cheknis AK, Sambol SP, ZukowskiWE, 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
87. Nakamura S, Nakashio S, Yamakawa K, Tanabe N, Nishida S. 1982. Carbohydrate fermentation by Clostridium difficile. Microbiol. Immunol. 26: 107-11
88. Ng KM, Ferreyra JA, Higginbottom SK, Lynch JB, Kashyap PC, et al. 2013. Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature 502: 96-99
89. Onderdonk AB, Cisneros RL, Bartlett JG. 1980. Clostridium difficile in gnotobiotic mice. Infect. Immun. 28: 277-82
90. Owens RC Jr, Donskey CJ, Gaynes RP, Loo VG, Muto CA. 2008. Antimicrobial-associated risk factors for Clostridium difficile infection. Clin. Infect. Dis. 46(Suppl. 1): S19-31
91. Pepin J, Saheb N, Coulombe MA, AlaryME, CorriveauMP, 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
92. Peterfreund GL, Vandivier LE, Sinha R, Marozsan AJ, Olson WC, et al. 2012. Succession in the gut microbiome following antibiotic and antibody therapies for Clostridium difficile. PLOS ONE 7: e46966
93. Proctor LM. 2011. The Human Microbiome Project in 2011 and beyond. Cell Host Microbe 10: 287-91
94. ReaMC, Sit CS, Clayton E, O'Connor PM, Whittal RM, et al. 2010. Thuricin CD, a posttranslationally modified bacteriocin with a narrow spectrum of activity against Clostridium difficile. PNAS 107: 9352-57
95. Reeves AE, Koenigsknecht MJ, Bergin IL, Young VB. 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
96. Reeves AE, Theriot CM, Bergin IL, HuffnagleGB, Schloss PD, YoungVB. 2011. The interplay between microbiome dynamics and pathogen dynamics in a murine model of Clostridium difficile infection. Gut Microbes 2: 145-58
97. Ridlon JM, Kang D-J, Hylemon PB. 2006. Bile salt biotransformations by human intestinal bacteria. J. Lipid Res. 47: 241-59
98. Robinson CD, Auchtung JM, Collins J, Britton RA. 2014. Epidemic Clostridium difficile strains demonstrate increased competitive fitness compared to nonepidemic isolates. Infect. Immun. 82: 2815-25
99. Rolfe RD. 1984. Role of volatile fatty acids in colonization resistance to Clostridium difficile. Infect. Immun. 45: 185-91
100. Romick-Rosendale LE, Goodpaster AM, Hanwright PJ, Patel NB, Wheeler ET, et al. 2009. NMRbased metabonomics analysis of mouse urine and fecal extracts following oral treatment with the broadspectrum antibiotic enrofloxacin (Baytril). Magn. Reson. Chem. 47(Suppl. 1): S36-46
101. Savage DC. 1977. Microbial ecology of the gastrointestinal tract. Annu. Rev. Microbiol. 31: 107-33
102. Scaria J, Chen JW, Useh N, He H, McDonough SP, et al. 2014. Comparative nutritional and chemical phenome of Clostridium difficile isolates determined using phenotype microarrays. Int. J. Infect. Dis. 27: 20-25
103. Schubert AM, Rogers MA, Ring C, Mogle J, Petrosino JP, et al. 2014. Microbiome data distinguish patients with Clostridium difficile infection and non-C. difficile-associated diarrhea from healthy controls. mBio 5: e01021-14
104. Seekatz AM, Aas J, Gessert CE, Rubin TA, Saman DM, et al. 2014. Recovery of the gut microbiome following fecal microbiota transplantation. mBio 5: e00893-14
105. Silvester KR, Englyst HN, Cummings JH. 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
106. Smith DG, Robinson HJ. 1945. The influence of streptomycin and streptothricin on the intestinal flora of mice. J. Bacteriol. 50: 613-21
107. Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, et al. 2013. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341: 569-73
108. Sonnenburg JL, Xu J, Leip DD, Chen CH, Westover BP, et al. 2005. Glycan foraging in vivo by an intestine-adapted bacterial symbiont. Science 307: 1955-59
109. Sorg JA. 2014. Microbial bile acid metabolic clusters: The bouncers at the bar. CellHostMicrobe 16: 551-52
110. Sorg JA, Sonenshein AL. 2008. Bile salts and glycine as cogerminants for Clostridium difficile spores. J. Bacteriol. 190: 2505-12
111. Sorg JA, Sonenshein AL. 2009. Chenodeoxycholate is an inhibitor of Clostridium difficile spore germination. J. Bacteriol. 191: 1115-17
112. Sorg JA, Sonenshein AL. 2010. Inhibiting the initiation of Clostridium difficile spore germination using analogs of chenodeoxycholic acid, a bile acid. J. Bacteriol. 192: 4983-90
113. SridharanGV, Choi K, Klemashevich C, WuC, Prabakaran D, et al. 2014. Prediction and quantification of bioactive microbiota metabolites in the mouse gut. Nat. Commun. 5: 5492
114. Stabler RA, He M, Dawson L, Martin M, Valiente E, 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
115. Stanley JD, Bartlett JG, Dart BW IV, Ashcraft JH. 2013. Clostridium difficile infection. Curr. Probl. Surg. 50: 302-37
116. Stecher B, Macpherson AJ, Hapfelmeier S, Kremer M, Stallmach T, HardtWD. 2005. Comparison of Salmonella enterica serovar Typhimurium colitis in germfree mice andmice pretreated with streptomycin. Infect. Immun. 73: 3228-41
117. Swann JR, Want EJ, Geier FM, Spagou K, Wilson ID, et al. 2011. Systemic gut microbial modulation of bile acid metabolism in host tissue compartments. PNAS 108(Suppl. 1): 4523-30
118. Tedesco FJ, Barton RW, Alpers DH. 1974. Clindamycin-associated colitis: A prospective study. Ann. Intern. Med. 81: 429-33
119. TheriotCM, KoenigsknechtMJ, Carlson PE Jr, HattonGE, Nelson AM, et al. 2014. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. Nat. Commun. 5: 3114
120. TremaroliV, Backhed F. 2012. Functional interactions between the gut microbiota and host metabolism. Nature 489: 242-49
121. van der Waaij D, Berghuis-de Vries JM, Lekkerkerk L-van derWees. 1971. Colonization resistance of the digestive tract in conventional and antibiotic-treated mice. J. Hyg. 69: 405-11
122. Van Houte J, Gibbons RJ. 1966. Studies of the cultivable flora of normal human feces. Antonie Van Leeuwenhoek 32: 212-22
123. vanNood E, Vrieze A, NieuwdorpM, Fuentes S, Zoetendal EG, et al. 2013. Duodenal infusion of donor feces for recurrent Clostridium difficile. N. Engl. J. Med. 368: 407-15
124. Vollaard EJ, Clasener HA. 1994. Colonization resistance. Antimicrob. Agents Chemother. 38: 409-14
125. Voth DE, Ballard JD. 2005. Clostridium difficile toxins: mechanism of action and role in disease. Clin. Microbiol. Rev. 18: 247-63
126. Vrieze A, OutC, Fuentes S, Jonker L, Reuling I, et al. 2014. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity. J. Hepatol. 60: 824-31
127. Warny M, Pepin J, Fang A, Killgore G, Thompson A, 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
128. Weingarden AR, Chen C, Bobr A, Yao D, Lu Y, 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
129. Wells JE, Hylemon PB. 2000. Identification and characterization of a bile acid 7-dehydroxylation operon in Clostridium sp. Strain TO-931, a highly active 7-dehydroxylating strain isolated from human feces. Appl. Environ. Microbiol. 66: 1107-13
130. Wensinck F, Ruseler-van Embden JG. 1971. The intestinal flora of colonization-resistant mice. J. Hyg. 69: 413-21
131. Wilson KH. 1993. The microecology of Clostridium difficile. Clin. Infect. Dis. 16(Suppl. 4): S214-18
132. Wilson KH, Kennedy MJ, Fekety FR. 1982. Use of sodium taurocholate to enhance spore recovery on a medium selective for Clostridium difficile. J. Clin. Microbiol. 15: 443-46
133. Wilson KH, Perini F. 1988. Role of competition for nutrients in suppression of Clostridium difficile by the colonic microflora. Infect. Immun. 56: 2610-14
134. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, et al. 2011. Linking long-term dietary patterns with gut microbial enterotypes. Science 334: 105-8
135. Yap IK, Li JV, Saric J, Martin FP, Davies H, 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
136. Young VB, Schmidt TM. 2004. Antibiotic-associated diarrhea accompanied by large-scale alterations in the composition of the fecal microbiota. J. Clin. Microbiol. 42: 1203-6
137. YoungVB, SchmidtTM. 2008. Overview of the gastrointestinalmicrobiota. Adv. Exp. Med. Biol. 635: 29-40
138. Zhao Y, Wu J, Li JV, Zhou NY, Tang H, Wang Y. 2013. Gut microbiota composition modifies fecal metabolic profiles in mice. J. Proteome Res. 12: 2987-99
139. Zheng X, Xie G, Zhao A, Zhao L, Yao C, et al. 2011. The footprints of gut microbial-mammalian co-metabolism. J. Proteome Res. 10: 5512-22