Gut microbiota changes associated with Clostridioides difficile infection and its various treatment strategies

References

• Magill SS, O’Leary E, Janelle SJ, Thompson DL, Dumyati G, Nadle J, Wilson LE, Kainer MA, Lynfield R, Greissman S, et al. Changes in prevalence of health care–associated infections in U.S. hospitals. Hospitals N Engl J Med. 2018;379(18):1732–13. doi:10.1056/NEJMoa1801550.
   PubMed Web of Science ®Google Scholar
• Guh AY, Mu Y, Winston LG, Johnston H, Olson D, Farley MM, Wilson LE, Holzbauer SM, Phipps EC, Dumyati GK, et al. Trends in U.S. burden of clostridioides difficile infection and outcomes. N Engl J Med. 2020;382(14):1320–1330. doi:10.1056/NEJMoa1910215.
   PubMed Web of Science ®Google Scholar
• Louie TJ, Miller MA, Mullane KM, Weiss K, Lentnek A, Golan Y, Gorbach S, Sears P, Shue Y-K. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364(5):422–431. doi:10.1056/NEJMoa0910812.
   PubMed Web of Science ®Google Scholar
• Cornely OA, Crook DW, Esposito R, Poirier A, Somero MS, Weiss K, Sears P, Gorbach S. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Dis. 2012;12(4):281–289. doi:10.1016/S1473-3099(11)70374-7.
   PubMed Web of Science ®Google Scholar
• Feuerstadt P, Stong L, Dahdal DN, Sacks N, Lang K, Nelson WW. Healthcare resource utilization and direct medical costs associated with index and recurrent Clostridioides difficile infection: a real-world data analysis. J Med Econ. 2020;23(6):603–609. doi:10.1080/13696998.2020.1724117.
   PubMed Web of Science ®Google Scholar
• Loo VG, Bourgault AM, Poirier L, Lamothe F, Michaud S, Turgeon N, Toye B, Beaudoin A, Frost EH, Gilca R, et al. Host and pathogen factors for Clostridium difficile infection and colonization. N Engl J Med. 2011;365(18):1693–1703. doi:10.1056/NEJMoa1012413.
   PubMed Web of Science ®Google Scholar
• Slimings C, Riley TV. Antibiotics and hospital-acquired Clostridium difficile infection: update of systematic review and meta-analysis. J Antimicrob Chemother. 2014;69(4):881–891. doi:10.1093/jac/dkt477.
   PubMed Web of Science ®Google Scholar
• Francino MP. Antibiotics and the human gut microbiome: dysbioses and accumulation of resistances. Front Microbiol. 2015;6:1543. doi:10.3389/fmicb.2015.01543.
   PubMed Web of Science ®Google Scholar
• Brown KA, Khanafer N, Daneman N, Fisman DN. Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection.Antimicrob Agents Chemother. 2013;57(5):2326–2332. doi:10.1128/AAC.02176-12.
   PubMed Web of Science ®Google Scholar
• Paredes-Sabja D, Shen A, Sorg JA. Clostridium difficile spore biology: sporulation, germination, and spore structural proteins. Trends Microbiol. 2014;22(7):406–416. doi:10.1016/j.tim.2014.04.003.
   PubMed Web of Science ®Google Scholar
• Sorg JA, Sonenshein AL. Bile salts and glycine as cogerminants for Clostridium difficile spores. J Bacteriol. 2008;190(7):2505–2512. doi:10.1128/JB.01765-07.
   PubMed Web of Science ®Google Scholar
• Smits WK, Lyras D, Lacy DB, Wilcox MH, Kuijper EJ. Clostridium difficile infection. Nat Rev Dis Primers. 2016;2(1):16020. doi:10.1038/nrdp.2016.20.
   PubMedGoogle Scholar
• Shen A. Clostridium difficile toxins: mediators of inflammation. J Innate Immun. 2012;4(2):149–158. doi:10.1159/000332946.
   PubMed Web of Science ®Google Scholar
• Di Bella S, Ascenzi P, Siarakas S, PetrosilloN, di Masi A. Clostridium difficile toxins A and B: insights into pathogenic properties and extraintestinal effects. Toxins (Basel). 2016;8(5):134. doi:10.3390/toxins8050134.
   PubMed Web of Science ®Google Scholar
• Chandrasekaran R, Lacy DB. The role of toxins in Clostridium difficile infection. FEMS Microbiol Rev. 2017;41(6):723–750. doi:10.1093/femsre/fux048.
   PubMed Web of Science ®Google Scholar
• Sehgal K, Khanna S. Gut microbiome and Clostridioides difficile infection: a closer look at the microscopic interface. Therap Adv Gastroenterol. 2021;14:1756284821994736. doi:10.1177/1756284821994736.
   Web of Science ®Google Scholar
• Zhang Y, Saint Fleur A, Feng H. The development of live biotherapeutics against Clostridioides difficile infection towards reconstituting gut microbiota. Gut Microbes. 2022;14(1):2052698. doi:10.1080/19490976.2022.2052698.
   PubMed Web of Science ®Google Scholar
• Galloway-Pena J, Hanson B. Tools for analysis of the microbiome. Dig Dis Sci. 2020;65(3):674–685. doi:10.1007/s10620-020-06091-y.
   PubMed Web of Science ®Google Scholar
• Daquigan N, Seekatz AM, Greathouse KL, Young VB, White JR. High-resolution profiling of the gut microbiome reveals the extent of Clostridium difficile burden. NPJ Biofilms Microbiomes. 2017;3(1):35. doi:10.1038/s41522-017-0043-0.
   PubMedGoogle Scholar
• Carlson TJ, Gonzales-Luna AJ. Antibiotic treatment pipeline for Clostridioides difficile Infection (CDI): a wide array of narrow-spectrum agents. Curr Infect Dis Rep. 2020;22(8):22. doi:10.1007/s11908-020-00730-1.
   Web of Science ®Google Scholar
• Gonzales-Luna AJ, Carlson TJ. Follow your Gut: microbiome-based approaches in the developmental pipeline for the prevention and adjunctive treatment of Clostridioides difficile Infection (CDI). Curr Infect Dis Rep. 2020;22(8):22. doi:10.1007/s11908-020-00729-8.
   Web of Science ®Google Scholar
• Food and Drug Administration (FDA). REBYOTA; 2022.
   Google Scholar
• Food and Drug Administration (FDA). VOWST; 2023.
   Google Scholar
• Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59–65. doi:10.1038/nature08821.
   PubMed Web of Science ®Google Scholar
• Human Microbiome Project C. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486:207–214.
   PubMed Web of Science ®Google Scholar
• Costea PI, Zeller G, Sunagawa S, Pelletier E, Alberti A, Levenez F, Tramontano M, Driessen M, Hercog R, Jung F-E, et al. Towards standards for human fecal sample processing in metagenomic studies. Nat Biotechnol. 2017;35(11):1069–1076. doi:10.1038/nbt.3960.
   PubMed Web of Science ®Google Scholar
• Shah N, Meisel JS, Pop M. Embracing ambiguity in the taxonomic classification of microbiome sequencing data. Front Genet. 2019;10:1022. doi:10.3389/fgene.2019.01022.
   PubMed Web of Science ®Google Scholar
• Asnicar F, Berry SE, Valdes AM, Nguyen LH, Piccinno G, Drew DA, Leeming E, Gibson R, Le Roy C, Khatib HA, et al. Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals. Nat Med. 2021;27(2):321–332. doi:10.1038/s41591-020-01183-8.
   PubMed Web of Science ®Google Scholar
• Pasolli E, Asnicar F, Manara S, Zolfo M, Karcher N, Armanini F, Beghini F, Manghi P, Tett A, Ghensi P, et al. Extensive unexplored human microbiome diversity revealed by over 150,000 genomes from metagenomes spanning age, geography, and lifestyle. Cell. 2019;176(3):649–62 e20. doi:10.1016/j.cell.2019.01.001.
   PubMed Web of Science ®Google Scholar
• Shanahan F, Ghosh TS, O’Toole PW. The healthy microbiome—what is the definition of a healthy gut microbiome? Gastroenterology. 2021;160(2):483–494. doi:10.1053/j.gastro.2020.09.057.
   PubMed Web of Science ®Google Scholar
• Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto J-M, et al. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174–180. doi:10.1038/nature09944.
   PubMed Web of Science ®Google Scholar
• Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA. Diversity of the human intestinal microbial flora. Science. 2005;308(5728):1635–1638. doi:10.1126/science.1110591.
   PubMed Web of Science ®Google Scholar
• Hopkins MJ, Macfarlane GT. Changes in predominant bacterial populations in human faeces with age and with Clostridium difficile infection. J Med Microbiol. 2002;51(5):448–454. doi:10.1099/0022-1317-51-5-448.
   PubMed Web of Science ®Google Scholar
• Chang JY, Antonopoulos DA, Kalra A, Tonelli A, Khalife WT, Schmidt TM, Young V. Decreased diversity of the fecal microbiome in recurrent clostridium difficile –associated diarrhea. J Infect Dis. 2008;197(3):435–438. doi:10.1086/525047.
   PubMed Web of Science ®Google Scholar
• Skraban J, Dzeroski S, Zenko B, Mongus D, Gangl S, Rupnik M, Popoff MR. Gut microbiota patterns associated with colonization of different Clostridium difficile ribotypes. PLos One. 2013;8(2):e58005. doi:10.1371/journal.pone.0058005.
   PubMed Web of Science ®Google Scholar
• Schubert AM, Rogers MA, Ring C, Mogle J, Petrosino JP, Young VB, Aronoff DM, Schloss PD. Microbiome data distinguish patients with Clostridium difficile infection and non-C. difficile-associated diarrhea from healthy controls. mBio. 2014;5(3):e01021–14. doi:10.1128/mBio.01021-14.
   PubMed Web of Science ®Google Scholar
• Zhang L, Dong D, Jiang C, Li Z, Wang X, Peng Y. Insight into alteration of gut microbiota in Clostridium difficile infection and asymptomatic C. difficile colonization. Anaerobe. 2015;34:1–7. doi:10.1016/j.anaerobe.2015.03.008.
   PubMed Web of Science ®Google Scholar
• Kim J, Cho Y, Seo MR, Bae MH, Kim B, Rho M, Pai H. Quantitative characterization of Clostridioides difficile population in the gut microbiome of patients with C. difficile infection and their association with clinical factors. Sci Rep. 2020;10(1):17608. doi:10.1038/s41598-020-74090-0.
   PubMed Web of Science ®Google Scholar
• Tannock GW, Munro K, Taylor C, Lawley B, Young W, Byrne B, Emery J, Louie T. A new macrocyclic antibiotic, fidaxomicin (OPT-80), causes less alteration to the bowel microbiota of Clostridium difficile-infected patients than does vancomycin. Microbiol (Reading). 2010;156(11):3354–3359. doi:10.1099/mic.0.042010-0.
   PubMedGoogle Scholar
• Louie TJ, Cannon K, Byrne B, Emery J, Ward L, Eyben M, Krulicki W. Fidaxomicin preserves the intestinal microbiome during and after treatment of Clostridium difficile infection (CDI) and reduces both toxin reexpression and recurrence of CDI. Clin Infect Dis. 2012;55(Suppl 2):S132–42. doi:10.1093/cid/cis338.
   PubMed Web of Science ®Google Scholar
• Thorpe CM, Kane AV, Chang J, Tai A, Vickers RJ, Snydman DR, Green J. Enhanced preservation of the human intestinal microbiota by ridinilazole, a novel Clostridium difficile-targeting antibacterial, compared to vancomycin. PLos One. 2018;13(8):e0199810. doi:10.1371/journal.pone.0199810.
   PubMed Web of Science ®Google Scholar
• Elvers KT, Wilson VJ, Hammond A, Duncan L, Huntley AL, Hay AD, van der Werf ET. Antibiotic-induced changes in the human gut microbiota for the most commonly prescribed antibiotics in primary care in the UK: a systematic review. BMJ Open. 2020;10(9):e035677. doi:10.1136/bmjopen-2019-035677.
   PubMed Web of Science ®Google Scholar
• Seekatz AM, Rao K, Santhosh K, Young VB. Dynamics of the fecal microbiome in patients with recurrent and nonrecurrent Clostridium difficile infection. Genome Med. 2016;8(1):47. doi:10.1186/s13073-016-0298-8.
   PubMedGoogle Scholar
• Lee AA, Rao K, Limsrivilai J, Gillilland M, Malamet B, Briggs E, Young VB, Higgins PDR. Temporal gut microbial changes predict recurrent clostridiodes difficile infection in patients with and without ulcerative colitis. Inflamm Bowel Dis. 2020;26(11):1748–1758. doi:10.1093/ibd/izz335.
   PubMed Web of Science ®Google Scholar
• Antharam VC, Li EC, Ishmael A, Sharma A, Mai V, Rand KH, Wang GP. Intestinal dysbiosis and depletion of butyrogenic bacteria in Clostridium difficile infection and nosocomial diarrhea. J Clin Microbiol. 2013;51(9):2884–2892. doi:10.1128/JCM.00845-13.
   PubMed Web of Science ®Google Scholar
• Vincent C, Stephens DA, Loo VG, Edens TJ, Behr MA, Dewar K, Manges AR. Reductions in intestinal Clostridiales precede the development of nosocomial Clostridium difficile infection. Microbiome. 2013;1(1):18. doi:10.1186/2049-2618-1-18.
   PubMed Web of Science ®Google Scholar
• Gerding DN, Johnson S, Peterson LR, Mulligan ME, Silva J, Jr. Clostridium difficile-associated diarrhea and colitis. Infect Control Hosp Epidemiol. 1995;16(8):459–477. doi:10.2307/30141083.
   PubMed Web of Science ®Google Scholar
• Bauer MP, Kuijper EJ, van Dissel JT. European society of clinical M, infectious D. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): treatment guidance document for Clostridium difficile infection (CDI). Clin Microbiol Infect. 2009;15(12):1067–1079. doi:10.1111/j.1469-0691.2009.03099.x.
   PubMed Web of Science ®Google Scholar
• Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31:431–455. doi:10.1086/651706.
   Google Scholar
• Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, McFarland LV, Mellow M, Zuckerbraun BS. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol Suppl. 2013;108(4):478–498. quiz 99. doi:10.1038/ajg.2013.4.
   Google Scholar
• Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007;45(3):302–307. doi:10.1086/519265.
   PubMed Web of Science ®Google Scholar
• Johnson S, Louie TJ, Gerding DN, Cornely OA, Chasan-Taber S, Fitts D, Gelone SP, Broom C, Davidson DM. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014;59(3):345–354. doi:10.1093/cid/ciu313.
   PubMed Web of Science ®Google Scholar
• Guery B, Menichetti F, Anttila V-J, Adomakoh N, Aguado JM, Bisnauthsing K, Georgopali A, Goldenberg SD, Karas A, Kazeem G, et al. Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial. Lancet Infect Dis. 2018;18(3):296–307. doi:10.1016/S1473-3099(17)30751-X.
   PubMed Web of Science ®Google Scholar
• Mikamo H, Tateda K, Yanagihara K, Kusachi S, Takesue Y, Miki T, Oizumi Y, Gamo K, Hashimoto A, Toyoshima J, et al. Efficacy and safety of fidaxomicin for the treatment of Clostridioides (Clostridium) difficile infection in a randomized, double-blind, comparative Phase III study in Japan. J Infect Chemother. 2018;24(9):744–752. doi:10.1016/j.jiac.2018.05.010.
   PubMed Web of Science ®Google Scholar
• Johnson S, Lavergne V, Skinner AM, Gonzales-Luna AJ, Garey KW, Kelly CP, Wilcox MH. Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 focused update guidelines on management of clostridioides difficile infection in adults. Clin Infect Dis. 2021;73(5):e1029–e1044. doi:10.1093/cid/ciab549.
   PubMed Web of Science ®Google Scholar
• van Prehn J, Reigadas E, Vogelzang EH, Bouza E, Hristea A, Guery B, Krutova M, Norén T, Allerberger F, Coia JE, et al. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin Microbiol Infect. 2021;Suppl 27:S1–S21. doi:10.1016/j.cmi.2021.09.038.
   Web of Science ®Google Scholar
• Edlund C, Barkholt L, Olsson-Liljequist B, Nord CE. Effect of vancomycin on intestinal flora of patients who previously received antimicrobial therapy. Clin Infect Dis. 1997;25(3):729–732. doi:10.1086/513755.
   PubMed Web of Science ®Google Scholar
• Vrieze A, Out C, Fuentes S, Jonker L, Reuling I, Kootte RS, van Nood E, Holleman F, Knaapen M, Romijn JA, et al. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity. J Hepatol. 2014;60(4):824–831. doi:10.1016/j.jhep.2013.11.034.
   PubMed Web of Science ®Google Scholar
• McPherson J, Hu C, Begum K, Wang W, Lancaster C, Gonzales-Luna AJ, Loveall C, Silverman MH, Alam MJ, Garey KW, et al. Functional and metagenomic evaluation of ibezapolstat for early evaluation of anti-recurrence effects in clostridioides difficile infection. Antimicrob Agents Chemother. 2022;66(8):e0224421. doi:10.1128/aac.02244-21.
   PubMed Web of Science ®Google Scholar
• Cannon K, Byrne B, Happe J, Wu K, Ward L, Chesnel L, Louie T. Enteric microbiome profiles during a randomized Phase 2 clinical trial of surotomycin versus vancomycin for the treatment of Clostridium difficile infection. J Antimicrob Chemother. 2017;72(12):3453–3461. doi:10.1093/jac/dkx318.
   PubMed Web of Science ®Google Scholar
• Louie TJ, Emery J, Krulicki W, Byrne B, Mah M. OPT-80 eliminates Clostridium difficile and is sparing of bacteroides species during treatment of C. difficile infection. Antimicrob Agents Chemother. 2009;53(1):261–263. doi:10.1128/AAC.01443-07.
   PubMed Web of Science ®Google Scholar
• Zimmermann P, Curtis N. The effect of antibiotics on the composition of the intestinal microbiota - a systematic review. J Infect. 2019;79(6):471–489. doi:10.1016/j.jinf.2019.10.008.
   PubMed Web of Science ®Google Scholar
• Vindigni SM, Surawicz CM. Fecal microbiota transplantation. Gastroenterol Clin North Am. 2017;46(1):171–185. doi:10.1016/j.gtc.2016.09.012.
   PubMed Web of Science ®Google Scholar
• Kelly CR, Fischer M, Allegretti JR, LaPlante K, Stewart DB, Limketkai BN, Stollman NH. ACG clinical guidelines: prevention, diagnosis, and treatment of clostridioides difficile infections. Am J Gastroenterol. 2021;116(6):1124–1147. doi:10.14309/ajg.0000000000001278.
   PubMed Web of Science ®Google Scholar
• Tariq R, Pardi DS, Bartlett MG, Khanna S. Low cure rates in controlled trials of fecal microbiota transplantation for recurrent clostridium difficile infection: a systematic review and meta-analysis. Clin Infect Dis. 2019;68(8):1351–1358. doi:10.1093/cid/ciy721.
   PubMed Web of Science ®Google Scholar
• Wang S, Xu M, Wang W, Cao X, Piao M, Khan S, Yan F, Cao H, Wang B. Systematic review: adverse events of fecal microbiota transplantation. PLoS One. 2016;11(8):e0161174. doi:10.1371/journal.pone.0161174.
   PubMed Web of Science ®Google Scholar
• DeFilipp Z, Bloom PP, Torres Soto M, Mansour MK, Sater MRA, Huntley MH, Turbett S, Chung RT, Chen Y-B, Hohmann EL, et al. Drug-resistant E. coli bacteremia transmitted by fecal microbiota transplant. N Engl J Med. 2019;381(21):2043–2050. doi:10.1056/NEJMoa1910437.
   PubMed Web of Science ®Google Scholar
• Food and Drug Amdinistration (FDA). Safety alert regarding use of fecal microbiota for transplantation and additional safety protections pertaining to SARS-CoV-2 and COVID-19. 2020. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/safety-alert-regarding-use-fecal-microbiota-transplantation-and-additional-safety-protections
   Google Scholar
• Park SY, Seo GS. Fecal microbiota transplantation: is it safe? Clin Endosc. 2021;54(2):157–160. doi:10.5946/ce.2021.072.
   PubMed Web of Science ®Google Scholar
• van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JFWM, Tijssen JGP, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407–415. doi:10.1056/NEJMoa1205037.
   PubMed Web of Science ®Google Scholar
• Song Y, Garg S, Girotra M, Maddox C, von Rosenvinge EC, Dutta A, Dutta S, Fricke WF. Microbiota dynamics in patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection. PLoS One. 2013;8(11):e81330. doi:10.1371/journal.pone.0081330.
   PubMed Web of Science ®Google Scholar
• Hamilton MJ, Weingarden AR, Unno T, Khoruts A, Sadowsky MJ. High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria. Gut Microbes. 2013;4(2):125–135. doi:10.4161/gmic.23571.
   PubMed Web of Science ®Google Scholar
• Seekatz AM, Aas J, Gessert CE, Rubin TA, Saman DM, Bakken JS, Young VB. Recovery of the gut microbiome following fecal microbiota transplantation. mBio. 2014;5(3):e00893–14. doi:10.1128/mBio.00893-14.
   PubMed Web of Science ®Google Scholar
• Shankar V, Hamilton MJ, Khoruts A, Kilburn A, Unno T, Paliy O, Sadowsky MJ. Species and genus level resolution analysis of gut microbiota in Clostridium difficile patients following fecal microbiota transplantation. Microbiome. 2014;2(1):13. doi:10.1186/2049-2618-2-13.
   PubMed Web of Science ®Google Scholar
• Staley C, Kelly CR, Brandt LJ, Khoruts A, Sadowsky MJ, Blaser MJ. Complete microbiota engraftment is not essential for recovery from recurrent clostridium difficile infection following fecal microbiota transplantation. mBio. 2016;7(6). doi:10.1128/mBio.01965-16.
   PubMed Web of Science ®Google Scholar
• Staley C, Hamilton MJ, Vaughn BP, Graiziger CT, Newman KM, Kabage AJ, Sadowsky MJ, Khoruts A. Successful resolution of recurrent clostridium difficile infection using freeze-dried, encapsulated fecal microbiota; pragmatic cohort study. Am J Gastroenterol. 2017;112(6):940–947. doi:10.1038/ajg.2017.6.
   PubMed Web of Science ®Google Scholar
• Khanna S, Vazquez-Baeza Y, Gonzalez A, Weiss S, Schmidt B, Muniz-Pedrogo DA, Rainey JF, Kammer P, Nelson H, Sadowsky M, et al. Changes in microbial ecology after fecal microbiota transplantation for recurrent C. difficile infection affected by underlying inflammatory bowel disease. Microbiome. 2017;5(1):55. doi:10.1186/s40168-017-0269-3.
   PubMedGoogle Scholar
• Aggarwala V, Mogno I, Li Z, Yang C, Britton GJ, Chen-Liaw A, Mitcham J, Bongers G, Gevers D, Clemente JC, et al. Precise quantification of bacterial strains after fecal microbiota transplantation delineates long-term engraftment and explains outcomes. Nature Microbiol. 2021;6(10):1309–1318. doi:10.1038/s41564-021-00966-0.
   PubMed Web of Science ®Google Scholar
• Louie T, Golan Y, Khanna S, Bobilev D, Erpelding N, Fratazzi C, Carini M, Menon R, Ruisi M, Norman JM, et al. VE303, a defined bacterial consortium, for prevention of recurrent clostridioides difficile infection: a randomized clinical trial. JAMA. 2023;329(16):1356–1366. doi:10.1001/jama.2023.4314.
   PubMed Web of Science ®Google Scholar
• Kao D, Wong K, Franz R, Cochrane K, Sherriff K, Chui L, Lloyd C, Roach B, Bai AD, Petrof EO, et al. The effect of a microbial ecosystem therapeutic (MET-2) on recurrent Clostridioides difficile infection: a phase 1, open-label, single-group trial. Lancet Gastroenterol Hepatol. 2021;6(4):282–291. doi:10.1016/S2468-1253(21)00007-8.
   PubMed Web of Science ®Google Scholar
• Food and Drug Administration (FDA). Early clinical trials with live biotherapeutic products: chemistry, manufacturing, and control information. 2016.
   Google Scholar
• Food and Drug Administration (FDA). Enforcement policy regarding investigational new drug requirements for use of fecal microbiota for transplantation to treat clostridioides difficile infection not responsive to standard therapies. 2022.
   Google Scholar
• Feuerstadt P, Louie TJ, Lashner B, Wang EEL, Diao L, Bryant JA, Sims M, Kraft CS, Cohen SH, Berenson CS, et al. SER-109, an oral microbiome therapy for recurrent clostridioides difficile infection. N Engl J Med. 2022;386(3):220–229. doi:10.1056/NEJMoa2106516.
   PubMed Web of Science ®Google Scholar
• Khanna S, Assi M, Lee C, Yoho D, Louie T, Knapple W, Aguilar H, Garcia-Diaz J, Wang GP, Berry SM, et al. Efficacy and safety of RBX2660 in PUNCH CD3, a phase III, randomized, double-blind, placebo-controlled trial with a bayesian primary analysis for the prevention of recurrent clostridioides difficile infection. Drugs. 2022;82(15):1527–1538. doi:10.1007/s40265-022-01797-x.
   PubMed Web of Science ®Google Scholar
• A trial of CP101 for the prevention of recurrent CDI (PRISM4). [ accessed 2023 Jan 10]. https://clinicaltrials.gov/ct2/show/record/NCT05153499.
   Google Scholar
• Orenstein R, Dubberke ER, Khanna S, Lee CH, Yoho D, Johnson S, Hecht G, DuPont HL, Gerding DN, Blount KF, et al. Durable reduction of Clostridioides difficile infection recurrence and microbiome restoration after treatment with RBX2660: results from an open-label phase 2 clinical trial. BMC Infect Dis. 2022;22(1):245. doi:10.1186/s12879-022-07256-y.
   PubMed Web of Science ®Google Scholar
• Cohen SH, Louie TJ, Sims M, Wang EEL, Memisoglu A, McGovern BH, von Moltke L. Extended Follow-up of microbiome therapeutic SER-109 through 24 weeks for recurrent clostridioides difficile infection in a randomized clinical trial. JAMA. 2022;328(20):2062–2064. doi:10.1001/jama.2022.16476.
   PubMed Web of Science ®Google Scholar
• Orenstein R, Dubberke E, Hardi R, Ray A, Mullane K, Pardi DS, Ramesh MS. Safety and durability of RBX2660 (microbiota suspension) for recurrent clostridium difficile infection: results of the PUNCH CD study. Clin Infect Dis. 2016;62(5):596–602. doi:10.1093/cid/civ938.
   PubMed Web of Science ®Google Scholar
• Dubberke ER, Lee CH, Orenstein R, Khanna S, Hecht G, Gerding DN. Results from a randomized, placebo-controlled clinical trial of a RBX2660—a microbiota-based drug for the prevention of recurrent clostridium difficile infection. Clin Infect Dis. 2018;67(8):1198–1204. doi:10.1093/cid/ciy259.
   PubMed Web of Science ®Google Scholar
• McGovern BH, Ford CB, Henn MR, Pardi DS, Khanna S, Hohmann EL, O’Brien EJ, Desjardins CA, Bernardo P, Wortman JR, et al. SER-109, an investigational microbiome drug to reduce recurrence after clostridioides difficile infection: lessons learned from a phase 2 trial. Clin Infect Dis. 2021;72(12):2132–2140. doi:10.1093/cid/ciaa387.
   PubMed Web of Science ®Google Scholar
• Khanna S, Pardi DS, Kelly CR, Kraft CS, Dhere T, Henn MR, Lombardo M-J, Vulic M, Ohsumi T, Winkler J, et al. A novel microbiome therapeutic increases gut microbial diversity and prevents recurrent clostridium difficile infection. J Infect Dis. 2016;214(2):173–181. doi:10.1093/infdis/jiv766.
   PubMed Web of Science ®Google Scholar
• REBYOTA. Prescribing information. Parsippany (NJ): Ferring Pharmaceuticals Inc; 2022.
   Google Scholar
• Blount KF, Shannon WD, Deych E, Jones C. Restoration of bacterial microbiome composition and diversity among treatment responders in a phase 2 trial of RBX2660: an investigational microbiome restoration therapeutic. Open Forum Infect Dis. 2019;6(4):ofz095. doi:10.1093/ofid/ofz095.
   PubMed Web of Science ®Google Scholar
• Langdon A, Schwartz DJ, Bulow C, Sun X, Hink T, Reske KA, Jones C, Burnham CAD, Dubberke ER, Dantas G, et al. Microbiota restoration reduces antibiotic-resistant bacteria gut colonization in patients with recurrent Clostridioides difficile infection from the open-label PUNCH CD study. Genome Med. 2021;13(1):28. doi:10.1186/s13073-021-00843-9.
   PubMed Web of Science ®Google Scholar
• Kwak S, Choi J, Hink T, Reske KA, Blount K, Jones C, Bost MH, Sun X, Burnham CAD, Dubberke ER, et al. Impact of investigational microbiota therapeutic RBX2660 on the gut microbiome and resistome revealed by a placebo-controlled clinical trial. Microbiome. 2020;8(1):125. doi:10.1186/s40168-020-00907-9.
   PubMed Web of Science ®Google Scholar
• Dubberke ER, Mullane KM, Gerding DN, Lee CH, Louie TJ, Guthertz H. Clearance of Vancomycin-Resistant enterococcus concomitant with administration of a microbiota-based drug targeted at recurrent clostridium difficile infection. Open Forum Infect Dis. 2016 3:ofw133.
   PubMed Web of Science ®Google Scholar
• Papazyan R, Fuchs B, Blount K, Gonzalez C, Shannon B. 1039. rapid restoration of bile acid compositions after treatment with RBX2660 for recurrent clostridioides difficile infection—results from the PUNCH CD3 phase 3 trial. Open Forum Infect Dis. 2021;8(Supplement_1):SS610–S. 1039. doi:10.1093/ofid/ofab466.1233.
   Google Scholar
• Theriot CM, Koenigsknecht MJ, Carlson PE, Jr., Hatton GE, Nelson AM, Li B, Huffnagle GB, Li J Z, Young VB. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. Nat Commun. 2014;5(1):3114. doi:10.1038/ncomms4114.
   PubMed Web of Science ®Google Scholar
• Buffie CG, Bucci V, Stein RR, McKenney PT, Ling L, Gobourne A, No D, Liu H, Kinnebrew M, Viale A, et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature. 2015;517(7533):205–208. doi:10.1038/nature13828.
   PubMed Web of Science ®Google Scholar
• Winston JA, Theriot CM. Impact of microbial derived secondary bile acids on colonization resistance against Clostridium difficile in the gastrointestinal tract. Anaerobe. 2016;41:44–50. doi:10.1016/j.anaerobe.2016.05.003.
   PubMed Web of Science ®Google Scholar
• Allegretti JR, Kearney S, Li N, Bogart E, Bullock K, Gerber GK, Bry L, Clish CB, Alm E, Korzenik JR, et al. Recurrent Clostridium difficile infection associates with distinct bile acid and microbiome profiles. Aliment Pharmacol Ther. 2016;43(11):1142–1153. doi:10.1111/apt.13616.
   PubMed Web of Science ®Google Scholar
• Tam J, Icho S, Utama E, Orrell KE, Gomez-Biagi RF, Theriot CM, Kroh HK, Rutherford SA, Lacy DB, Melnyk RA, et al. Intestinal bile acids directly modulate the structure and function of C. difficile TcdB toxin. Proc Natl Acad Sci U S A. 2020;117(12):6792–6800. doi:10.1073/pnas.1916965117.
   PubMed Web of Science ®Google Scholar
• McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, et al. Clinical practice guidelines for clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):e1–e48. doi:10.1093/cid/cix1085.
   PubMed Web of Science ®Google Scholar
• Gerding DN, Kelly CP, Rahav G, Lee C, Dubberke ER, Kumar PN, Yacyshyn B, Kao D, Eves K, Ellison MC, et al. Bezlotoxumab for prevention of recurrent clostridium difficile infection in patients at increased risk for recurrence. Clin Infect Dis. 2018;67(5):649–656. doi:10.1093/cid/ciy171.
   PubMed Web of Science ®Google Scholar
• Johnson S, Lavergne V, Skinner AM, Gonzales-Luna AJ, Garey KW, Kelly CP, Wilcox MH. Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 focused update guidelines on management of clostridioides difficile infection in adults. Clin Infect Dis. 2021;73(5):755–757. doi:10.1093/cid/ciab718.
   PubMedGoogle Scholar
• Freedman SB, Schnadower D, Tarr PI. The probiotic conundrum: regulatory confusion, conflicting studies, and safety concerns. JAMA. 2020;323(9):823–824. doi:10.1001/jama.2019.22268.
   PubMed Web of Science ®Google Scholar
• Goldenberg JZ, Yap C, Lytvyn L, Lo CK, Beardsley J, Mertz D, Johnston BC. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017;12(12). CD006095. doi:10.1002/14651858.CD006095.pub4.
   PubMedGoogle Scholar
• Allegretti JR, Mullish BH, Kelly C, Fischer M. The evolution of the use of faecal microbiota transplantation and emerging therapeutic indications. Lancet. 2019;394(10196):420–431. doi:10.1016/S0140-6736(19)31266-8.
   PubMed Web of Science ®Google Scholar
• Cordaillat-Simmons M, Rouanet A, Pot B. Live biotherapeutic products: the importance of a defined regulatory framework. Exp Mol Med. 2020;52(9):1397–1406. doi:10.1038/s12276-020-0437-6.
   PubMed Web of Science ®Google Scholar