{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:49:14Z","timestamp":1792784954264,"version":"4.5.0"},"reference-count":69,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Vedanta Biosciences, Sponsored research agreement"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2025,1]]},"DOI":"10.1038\/s41591-024-03337-4","type":"journal-article","created":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T05:01:57Z","timestamp":1735794117000},"page":"223-234","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Multi-omic profiling a defined bacterial consortium for treatment of recurrent Clostridioides difficile infection"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4767-0971","authenticated-orcid":false,"given":"Rajita","family":"Menon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakti K.","family":"Bhattarai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3645-2909","authenticated-orcid":false,"given":"Emily","family":"Crossette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda L.","family":"Prince","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernat","family":"Olle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L.","family":"Silber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanni","family":"Bucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremiah","family":"Faith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5049-8415","authenticated-orcid":false,"given":"Jason M.","family":"Norman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,2]]},"reference":[{"key":"3337_CR1","doi-asserted-by":"crossref","DOI":"10.1186\/s12879-021-06147-y","volume":"21","author":"E Finn","year":"2021","unstructured":"Finn, E., Andersson, F. L. & Madin-Warburton, M. Burden of Clostridioides difficile infection (CDI)\u2014a systematic review of the epidemiology of primary and recurrent CDI. BMC Infect. Dis. 21, 456 (2021).","journal-title":"BMC Infect. Dis."},{"key":"3337_CR2","doi-asserted-by":"crossref","DOI":"10.1186\/s12879-023-08096-0","volume":"23","author":"P Feuerstadt","year":"2023","unstructured":"Feuerstadt, P., Theriault, N. & Tillotson, G. The burden of CDI in the United States: a multifactorial challenge. BMC Infect. Dis. 23, 132 (2023).","journal-title":"BMC Infect. Dis."},{"key":"3337_CR3","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1056\/NEJMoa1910215","volume":"382","author":"AY Guh","year":"2020","unstructured":"Guh, A. Y. et al. Trends in U.S. burden of Clostridioides difficile infection and outcomes. N. Engl. J. Med. 382, 1320\u20131330 (2020).","journal-title":"N. Engl. J. Med."},{"key":"3337_CR4","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1056\/NEJMoa2106516","volume":"386","author":"P Feuerstadt","year":"2022","unstructured":"Feuerstadt, P. et al. SER-109, an oral microbiome therapy for recurrent Clostridioides difficile infection. N. Engl. J. Med. 386, 220\u2013229 (2022).","journal-title":"N. Engl. J. Med."},{"key":"3337_CR5","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1007\/s40265-022-01797-x","volume":"82","author":"S Khanna","year":"2022","unstructured":"Khanna, S. 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 82, 1527\u20131538 (2022).","journal-title":"Drugs"},{"key":"3337_CR6","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1056\/NEJMoa1205037","volume":"368","author":"E van Nood","year":"2013","unstructured":"van Nood, E. et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N. Engl. J. Med. 368, 407\u2013415 (2013).","journal-title":"N. Engl. J. Med."},{"key":"3337_CR7","doi-asserted-by":"crossref","first-page":"ofx243","DOI":"10.1093\/ofid\/ofx243","volume":"4","author":"LJ Craven","year":"2017","unstructured":"Craven, L. J., Nair Parvathy, S., Tat-Ko, J., Burton, J. P. & Silverman, M. S. Extended screening costs associated with selecting donors for fecal microbiota transplantation for treatment of metabolic syndrome-associated diseases. Open Forum Infect. Dis. 4, ofx243 (2017).","journal-title":"Open Forum Infect. Dis."},{"key":"3337_CR8","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1056\/NEJMoa1910437","volume":"381","author":"Z DeFilipp","year":"2019","unstructured":"DeFilipp, Z. et al. Drug-resistant E. coli bacteremia transmitted by fecal microbiota transplant. N. Engl. J. Med. 381, 2043\u20132050 (2019).","journal-title":"N. Engl. J. Med."},{"key":"3337_CR9","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1002\/jmv.25825","volume":"92","author":"Y Chen","year":"2020","unstructured":"Chen, Y. et al. The presence of SARS-CoV-2 RNA in the feces of COVID-19 patients. J. Med. Virol. 92, 833\u2013840 (2020).","journal-title":"J. Med. Virol."},{"key":"3337_CR10","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.chom.2022.03.016","volume":"30","author":"M Dsouza","year":"2022","unstructured":"Dsouza, M. et al. Colonization of the live biotherapeutic product VE303 and modulation of the microbiota and metabolites in healthy volunteers. Cell Host Microbe 30, 583\u2013598.e8 (2022).","journal-title":"Cell Host Microbe"},{"key":"3337_CR11","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1001\/jama.2023.4314","volume":"329","author":"T Louie","year":"2023","unstructured":"Louie, T. et al. VE303, a defined bacterial consortium, for prevention of recurrent Clostridioides difficile infection: a randomized clinical trial. JAMA 329, 1356\u20131366 (2023).","journal-title":"JAMA"},{"key":"3337_CR12","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1017\/ice.2014.88","volume":"36","author":"A Deshpande","year":"2015","unstructured":"Deshpande, A. et al. Risk factors for recurrent Clostridium difficile infection: a systematic review and meta-analysis. Infect. Control Hosp. Epidemiol. 36, 452\u2013460 (2015).","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"3337_CR13","doi-asserted-by":"crossref","first-page":"16","DOI":"10.5009\/gnl18071","volume":"13","author":"JH Song","year":"2019","unstructured":"Song, J. H. & Kim, Y. S. Recurrent Clostridium difficile infection: risk factors, treatment, and prevention. Gut Liver 13, 16\u201324 (2019).","journal-title":"Gut Liver"},{"key":"3337_CR14","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1053\/j.gastro.2014.01.059","volume":"146","author":"RA Britton","year":"2014","unstructured":"Britton, R. A. & Young, V. B. Role of the intestinal microbiota in resistance to colonization by Clostridium difficile. Gastroenterology 146, 1547\u20131553 (2014).","journal-title":"Gastroenterology"},{"key":"3337_CR15","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1080\/13696998.2020.1724117","volume":"23","author":"P Feuerstadt","year":"2020","unstructured":"Feuerstadt, P. et al. Healthcare resource utilization and direct medical costs associated with index and recurrent Clostridioides difficile infection: a real-world data analysis. J. Med. Econ. 23, 603\u2013609 (2020).","journal-title":"J. Med. Econ."},{"key":"3337_CR16","doi-asserted-by":"crossref","first-page":"e60","DOI":"10.1017\/ash.2022.2","volume":"2","author":"P Feuerstadt","year":"2022","unstructured":"Feuerstadt, P., Nelson, W. W., Teigland, C. & Dahdal, D. N. Clinical burden of recurrent Clostridioides difficile infection in the medicare population: a real-world claims analysis. Antimicrob. Steward. Healthc. Epidemiol. 2, e60 (2022).","journal-title":"Antimicrob. Steward. Healthc. Epidemiol."},{"key":"3337_CR17","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/widm.1072","volume":"2","author":"A-L Boulesteix","year":"2012","unstructured":"Boulesteix, A.-L., Janitza, S., Kruppa, J. & K\u00f6nig, I. R. Overview of random forest methodology and practical guidance with emphasis on computational biology and bioinformatics. WIREs Data Min. Knowl. Discov. 2, 493\u2013507 (2012).","journal-title":"WIREs Data Min. Knowl. Discov."},{"key":"3337_CR18","doi-asserted-by":"crossref","DOI":"10.1186\/2049-2618-1-11","volume":"1","author":"A Statnikov","year":"2013","unstructured":"Statnikov, A. et al. A comprehensive evaluation of multicategory classification methods for microbiomic data. Microbiome 1, 11 (2013).","journal-title":"Microbiome"},{"key":"3337_CR19","doi-asserted-by":"crossref","first-page":"e76269","DOI":"10.1371\/journal.pone.0076269","volume":"8","author":"T Abujamel","year":"2013","unstructured":"Abujamel, T. et al. Defining the vulnerable period for re-establishment of Clostridium difficile colonization after treatment of C. difficile infection with oral vancomycin or metronidazole. PLoS ONE 8, e76269 (2013).","journal-title":"PLoS ONE"},{"key":"3337_CR20","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.ijantimicag.2015.03.016","volume":"46","author":"AK Thabit","year":"2015","unstructured":"Thabit, A. K. & Nicolau, D. P. Impact of vancomycin faecal concentrations on clinical and microbiological outcomes in Clostridium difficile infection. Int. J. Antimicrob. Agents 46, 205\u2013208 (2015).","journal-title":"Int. J. Antimicrob. Agents"},{"key":"3337_CR21","doi-asserted-by":"crossref","first-page":"82","DOI":"10.2146\/ajhp080434","volume":"66","author":"M Rybak","year":"2009","unstructured":"Rybak, M. et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am. J. Health Syst. Pharm. 66, 82\u201398 (2009).","journal-title":"Am. J. Health Syst. Pharm."},{"key":"3337_CR22","doi-asserted-by":"crossref","first-page":"e30","DOI":"10.1017\/eds.2022.34","volume":"1","author":"U Bradter","year":"2022","unstructured":"Bradter, U. et al. Variable ranking and selection with random forest for unbalanced data. Environ. Data Sci. 1, e30 (2022).","journal-title":"Environ. Data Sci."},{"key":"3337_CR23","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez, A. et al. Learning From Imbalanced Data Sets (Springer, 2018).","DOI":"10.1007\/978-3-319-98074-4"},{"key":"3337_CR24","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.cmi.2021.09.026","volume":"28","author":"TM van Rossen","year":"2022","unstructured":"van Rossen, T. M. et al. Prognostic factors for severe and recurrent Clostridioides difficile infection: a systematic review. Clin. Microbiol. Infect. 28, 321\u2013331 (2022).","journal-title":"Clin. Microbiol. Infect."},{"key":"3337_CR25","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1016\/j.cgh.2013.04.050","volume":"11","author":"R Shivashankar","year":"2013","unstructured":"Shivashankar, R. et al. Clinical factors associated with development of severe-complicated Clostridium difficile infection. Clin. Gastroenterol. Hepatol. 11, 1466\u20131471 (2013).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"3337_CR26","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.14309\/ajg.0000000000001278","volume":"116","author":"CR Kelly","year":"2021","unstructured":"Kelly, C. R. et al. ACG clinical guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections. Am. J. Gastroenterol. 116, 1124\u20131147 (2021).","journal-title":"Am. J. Gastroenterol."},{"key":"3337_CR27","doi-asserted-by":"crossref","first-page":"e0118322","DOI":"10.1128\/mbio.01183-22","volume":"13","author":"NA Lesniak","year":"2022","unstructured":"Lesniak, N. A. et al. The gut bacterial community potentiates Clostridioides difficile infection severity. mBio 13, e0118322 (2022).","journal-title":"mBio"},{"key":"3337_CR28","doi-asserted-by":"crossref","first-page":"677","DOI":"10.3390\/microorganisms8050677","volume":"8","author":"MJT Crobach","year":"2020","unstructured":"Crobach, M. J. T. et al. The bacterial gut microbiota of adult patients infected, colonized or noncolonized by Clostridioides difficile. Microorganisms 8, 677 (2020).","journal-title":"Microorganisms"},{"key":"3337_CR29","doi-asserted-by":"crossref","first-page":"175628482110177","DOI":"10.1177\/17562848211017725","volume":"14","author":"BH Mullish","year":"2021","unstructured":"Mullish, B. H. & Allegretti, J. R. The contribution of bile acid metabolism to the pathogenesis of Clostridioides difficile infection. Therap. Adv. Gastroenterol 14, 17562848211017725 (2021).","journal-title":"Therap. Adv. Gastroenterol"},{"key":"3337_CR30","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms4114","volume":"5","author":"CM Theriot","year":"2014","unstructured":"Theriot, C. M. et al. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. Nat. Commun. 5, 3114 (2014).","journal-title":"Nat. Commun."},{"key":"3337_CR31","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1128\/JB.01765-07","volume":"190","author":"JA Sorg","year":"2008","unstructured":"Sorg, J. A. & Sonenshein, A. L. Bile salts and glycine as cogerminants for Clostridium difficile spores. J. Bacteriol. 190, 2505\u20132512 (2008).","journal-title":"J. Bacteriol."},{"key":"3337_CR32","doi-asserted-by":"crossref","first-page":"e1007581","DOI":"10.1371\/journal.ppat.1007581","volume":"15","author":"MH Foley","year":"2019","unstructured":"Foley, M. H., O\u2019Flaherty, S., Barrangou, R. & Theriot, C. M. Bile salt hydrolases: gatekeepers of bile acid metabolism and host-microbiome crosstalk in the gastrointestinal tract. PLoS Pathog. 15, e1007581 (2019).","journal-title":"PLoS Pathog."},{"key":"3337_CR33","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.anaerobe.2017.03.004","volume":"45","author":"R Thanissery","year":"2017","unstructured":"Thanissery, R., Winston, J. A. & Theriot, C. M. Inhibition of spore germination, growth, and toxin activity of clinically relevant C. difficile strains by gut microbiota derived secondary bile acids. Anaerobe 45, 86\u2013100 (2017).","journal-title":"Anaerobe"},{"key":"3337_CR34","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.chembiol.2018.10.003","volume":"26","author":"JD Kang","year":"2019","unstructured":"Kang, J. D. et al. Bile acid 7\u03b1-dehydroxylating gut bacteria secrete antibiotics that inhibit Clostridium difficile: role of secondary bile acids. Cell Chem. Biol. 26, 27\u201334.e4 (2019).","journal-title":"Cell Chem. Biol."},{"key":"3337_CR35","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.celrep.2019.03.054","volume":"27","author":"JL Fachi","year":"2019","unstructured":"Fachi, J. L. et al. Butyrate protects mice from Clostridium difficile-induced colitis through an HIF-1-dependent mechanism. Cell Rep. 27, 750\u2013761 (2019).","journal-title":"Cell Rep."},{"key":"3337_CR36","doi-asserted-by":"publisher","unstructured":"Minot, S. S., Krumm, N. & Greenfield, N. B. One Codex: a sensitive and accurate data platform for genomic microbial identification. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/027607 (2015).","DOI":"10.1101\/027607"},{"key":"3337_CR37","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1093\/infdis\/jiv766","volume":"214","author":"S Khanna","year":"2016","unstructured":"Khanna, S. et al. A novel microbiome therapeutic increases gut microbial diversity and prevents recurrent Clostridium difficile infection. J. Infect. Dis. 214, 173\u2013181 (2016).","journal-title":"J. Infect. Dis."},{"key":"3337_CR38","doi-asserted-by":"crossref","first-page":"781","DOI":"10.3390\/pathogens11070781","volume":"11","author":"E Martinez","year":"2022","unstructured":"Martinez, E., Taminiau, B., Rodriguez, C. & Daube, G. Gut microbiota composition associated with Clostridioides difficile colonization and infection. Pathogens 11, 781 (2022).","journal-title":"Pathogens"},{"key":"3337_CR39","doi-asserted-by":"crossref","first-page":"368","DOI":"10.5851\/kosfa.2017.37.3.368","volume":"37","author":"B Yun","year":"2017","unstructured":"Yun, B., Song, M., Park, D.-J. & Oh, S. Beneficial effect of Bifidobacterium longum ATCC 15707 on survival rate of Clostridium difficile infection in mice. Korean J. Food Sci. Anim. Resour. 37, 368\u2013375 (2017).","journal-title":"Korean J. Food Sci. Anim. Resour."},{"key":"3337_CR40","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1111\/apt.13750","volume":"44","author":"S Khanna","year":"2016","unstructured":"Khanna, S. et al. Gut microbiome predictors of treatment response and recurrence in primary Clostridium difficile infection. Aliment. Pharmacol. Ther. 44, 715\u2013727 (2016).","journal-title":"Aliment. Pharmacol. Ther."},{"key":"3337_CR41","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.jinf.2018.06.006","volume":"77","author":"S Larcombe","year":"2018","unstructured":"Larcombe, S., Hutton, M. L., Riley, T. V., Abud, H. E. & Lyras, D. Diverse bacterial species contribute to antibiotic-associated diarrhoea and gastrointestinal damage. J. Infect. 77, 417\u2013426 (2018).","journal-title":"J. Infect."},{"key":"3337_CR42","doi-asserted-by":"crossref","first-page":"e0260667","DOI":"10.1371\/journal.pone.0260667","volume":"16","author":"H Motamedi","year":"2021","unstructured":"Motamedi, H. et al. A worldwide systematic review and meta-analysis of bacteria related to antibiotic-associated diarrhea in hospitalized patients. PLoS ONE 16, e0260667 (2021).","journal-title":"PLoS ONE"},{"key":"3337_CR43","doi-asserted-by":"crossref","first-page":"e74","DOI":"10.1086\/592074","volume":"47","author":"I Zollner-Schwetz","year":"2008","unstructured":"Zollner-Schwetz, I. et al. Role of Klebsiella oxytoca in antibiotic-associated diarrhea. Clin. Infect. Dis. 47, e74\u2013e78 (2008).","journal-title":"Clin. Infect. Dis."},{"key":"3337_CR44","doi-asserted-by":"crossref","first-page":"86","DOI":"10.4161\/gmic.27131","volume":"5","author":"CM Theriot","year":"2014","unstructured":"Theriot, C. M. & Young, V. B. Microbial and metabolic interactions between the gastrointestinal tract and Clostridium difficile infection. Gut Microbes 5, 86\u201395 (2014).","journal-title":"Gut Microbes"},{"key":"3337_CR45","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/s12876-018-0860-5","volume":"18","author":"JR-M Brown","year":"2018","unstructured":"Brown, J. R.-M. et al. Changes in microbiota composition, bile and fatty acid metabolism, in successful faecal microbiota transplantation for Clostridioides difficile infection. BMC Gastroenterol. 18, 131 (2018).","journal-title":"BMC Gastroenterol."},{"key":"3337_CR46","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.anaerobe.2018.04.001","volume":"53","author":"AM Seekatz","year":"2018","unstructured":"Seekatz, A. M. et al. Restoration of short chain fatty acid and bile acid metabolism following fecal microbiota transplantation in patients with recurrent Clostridium difficile infection. Anaerobe 53, 64\u201373 (2018).","journal-title":"Anaerobe"},{"key":"3337_CR47","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1136\/gutjnl-2018-317842","volume":"68","author":"BH Mullish","year":"2019","unstructured":"Mullish, B. H. et al. Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent Clostridioides difficile infection. Gut 68, 1791\u20131800 (2019).","journal-title":"Gut"},{"key":"3337_CR48","doi-asserted-by":"crossref","DOI":"10.1186\/s40168-021-01101-1","volume":"9","author":"DV Guzior","year":"2021","unstructured":"Guzior, D. V. & Quinn, R. A. Review: microbial transformations of human bile acids. Microbiome 9, 140 (2021).","journal-title":"Microbiome"},{"key":"3337_CR49","doi-asserted-by":"crossref","first-page":"e0080521","DOI":"10.1128\/msystems.00805-21","volume":"6","author":"LN Lucas","year":"2021","unstructured":"Lucas, L. N. et al. Dominant bacterial phyla from the human gut show widespread ability to transform and conjugate bile acids. mSystems 6, e0080521 (2021).","journal-title":"mSystems"},{"key":"3337_CR50","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.tiv.2012.12.020","volume":"27","author":"JI Barrasa","year":"2013","unstructured":"Barrasa, J. I., Olmo, N., Lizarbe, M. A. & Turnay, J. Bile acids in the colon, from healthy to cytotoxic molecules. Toxicol. In Vitro 27, 964\u2013977 (2013).","journal-title":"Toxicol. In Vitro"},{"key":"3337_CR51","doi-asserted-by":"crossref","first-page":"e00045-20","DOI":"10.1128\/IAI.00045-20","volume":"88","author":"JA Winston","year":"2020","unstructured":"Winston, J. A. et al. Ursodeoxycholic acid (UDCA) mitigates the host inflammatory response during Clostridioides difficile infection by altering gut bile acids. Infect. Immun. 88, e00045-20 (2020).","journal-title":"Infect. Immun."},{"key":"3337_CR52","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1016\/j.drudis.2022.03.021","volume":"27","author":"J Chen","year":"2022","unstructured":"Chen, J. et al. Targeting Clostridioides difficile: new uses for old drugs. Drug Discov. Today 27, 1862\u20131873 (2022).","journal-title":"Drug Discov. Today"},{"key":"3337_CR53","doi-asserted-by":"crossref","unstructured":"Smith, A. B. et al. Enterococci enhance Clostridioides difficile pathogenesis. Nature 611, 780\u2013786 (2022).","DOI":"10.1038\/s41586-022-05438-x"},{"key":"3337_CR54","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-023-43671-8","volume":"14","author":"M Bosnjak","year":"2023","unstructured":"Bosnjak, M. et al. Multi-omics analysis of hospital-acquired diarrhoeal patients reveals biomarkers of enterococcal proliferation and Clostridioides difficile infection. Nat. Commun. 14, 7737 (2023).","journal-title":"Nat. Commun."},{"key":"3337_CR55","doi-asserted-by":"crossref","first-page":"2094672","DOI":"10.1080\/19490976.2022.2094672","volume":"14","author":"AM Aguirre","year":"2022","unstructured":"Aguirre, A. M. & Sorg, J. A. Gut associated metabolites and their roles in Clostridioides difficile pathogenesis. Gut Microbes 14, 2094672 (2022).","journal-title":"Gut Microbes"},{"key":"3337_CR56","doi-asserted-by":"crossref","first-page":"102585","DOI":"10.1016\/j.anaerobe.2022.102585","volume":"75","author":"Z-R Ouyang","year":"2022","unstructured":"Ouyang, Z.-R., Niu, X.-R., Wang, W.-G. & Zhao, J.-H. The role of short-chain fatty acids in Clostridioides difficile infection: a review. Anaerobe 75, 102585 (2022).","journal-title":"Anaerobe"},{"key":"3337_CR57","doi-asserted-by":"crossref","first-page":"e00570-22","DOI":"10.1128\/iai.00570-22","volume":"91","author":"DA Pensinger","year":"2023","unstructured":"Pensinger, D. A. et al. Butyrate differentiates permissiveness to Clostridioides difficile infection and influences growth of diverse C. difficile isolates. Infect. Immun. 91, e00570-22 (2023).","journal-title":"Infect. Immun."},{"key":"3337_CR58","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41579-022-00805-x","volume":"21","author":"SL Collins","year":"2023","unstructured":"Collins, S. L., Stine, J. G., Bisanz, J. E., Okafor, C. D. & Patterson, A. D. Bile acids and the gut microbiota: metabolic interactions and impacts on disease. Nat. Rev. Microbiol. 21, 236\u2013247 (2023).","journal-title":"Nat. Rev. Microbiol."},{"key":"3337_CR59","doi-asserted-by":"crossref","first-page":"4983","DOI":"10.1128\/JB.00610-10","volume":"192","author":"JA Sorg","year":"2010","unstructured":"Sorg, J. A. & Sonenshein, A. L. Inhibiting the initiation of Clostridium difficile spore germination using analogs of chenodeoxycholic acid, a bile acid. J. Bacteriol. 192, 4983\u20134990 (2010).","journal-title":"J. Bacteriol."},{"key":"3337_CR60","doi-asserted-by":"crossref","first-page":"e00045-15","DOI":"10.1128\/mSphere.00045-15","volume":"1","author":"CM Theriot","year":"2016","unstructured":"Theriot, C. M., Bowman, A. A. & Young, V. B. Antibiotic-induced alterations of the gut microbiota alter secondary bile acid production and allow for Clostridium difficile spore germination and outgrowth in the large intestine. mSphere 1, e00045-15 (2016).","journal-title":"mSphere"},{"key":"3337_CR61","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.3389\/fmicb.2018.01970","volume":"9","author":"JD Hofmann","year":"2018","unstructured":"Hofmann, J. D. et al. Metabolic reprogramming of Clostridioides difficile during the stationary phase with the induction of toxin production. Front. Microbiol. 9, 1970 (2018).","journal-title":"Front. Microbiol."},{"key":"3337_CR62","doi-asserted-by":"publisher","unstructured":"Carr, A., Baliga, N. S., Diener, C. & Gibbons, S. M. Personalized Clostridioides difficile engraftment risk prediction and probiotic therapy assessment in the human gut. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2023.04.28.538771 (2024).","DOI":"10.1101\/2023.04.28.538771"},{"key":"3337_CR63","doi-asserted-by":"crossref","first-page":"e1009442","DOI":"10.1371\/journal.pcbi.1009442","volume":"17","author":"H Mallick","year":"2021","unstructured":"Mallick, H. et al. Multivariable association discovery in population-scale meta-omics studies. PLoS Comput. Biol. 17, e1009442 (2021).","journal-title":"PLoS Comput. Biol."},{"key":"3337_CR64","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.1093\/bioinformatics\/btw308","volume":"32","author":"EZ Chen","year":"2016","unstructured":"Chen, E. Z. & Li, H. A two-part mixed-effects model for analyzing longitudinal microbiome compositional data. Bioinformatics 32, 2611\u20132617 (2016).","journal-title":"Bioinformatics"},{"key":"3337_CR65","doi-asserted-by":"crossref","first-page":"dmm048025","DOI":"10.1242\/dmm.048025","volume":"15","author":"JI Murphy","year":"2022","unstructured":"Murphy, J. I., Weaver, N. E. & Hendricks, A. E. Accessible analysis of longitudinal data with linear mixed effects models. Dis. Model. Mech. 15, dmm048025 (2022).","journal-title":"Dis. Model. Mech."},{"key":"3337_CR66","doi-asserted-by":"crossref","unstructured":"Therneau, T. M. & Grambsch, P. M. Modeling Survival Data: Extending the Cox Model (Springer, 2000).","DOI":"10.1007\/978-1-4757-3294-8"},{"key":"3337_CR67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v036.i11","volume":"36","author":"MB Kursa","year":"2010","unstructured":"Kursa, M. B. & Rudnicki, W. R. Feature selection with the Boruta package. J. Stat. Softw. 36, 1\u201313 (2010).","journal-title":"J. Stat. Softw."},{"key":"3337_CR68","doi-asserted-by":"crossref","first-page":"e1004557","DOI":"10.1371\/journal.pcbi.1004557","volume":"11","author":"J Kaminski","year":"2015","unstructured":"Kaminski, J. et al. High-specificity targeted functional profiling in microbial communities with ShortBRED. PLoS Comput. Biol. 11, e1004557 (2015).","journal-title":"PLoS Comput. Biol."},{"key":"3337_CR69","doi-asserted-by":"crossref","DOI":"10.1186\/s40168-019-0689-3","volume":"7","author":"A Heinken","year":"2019","unstructured":"Heinken, A. et al. Systematic assessment of secondary bile acid metabolism in gut microbes reveals distinct metabolic capabilities in inflammatory bowel disease. Microbiome 7, 75 (2019).","journal-title":"Microbiome"}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41591-024-03337-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-024-03337-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-024-03337-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T18:05:04Z","timestamp":1737482704000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-024-03337-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":69,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["3337"],"URL":"https:\/\/doi.org\/10.1038\/s41591-024-03337-4","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"1 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 October 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"R.M., E.C., A.L.P., B.O., J.L.S. and J.M.N. are employees of Vedanta Biosciences and have an equity interest in the company. Vedanta Biosciences holds patents related to this work. J.F. and V.B. are members of the scientific advisory board of Vedanta Biosciences; J.F. has an equity interest in the company. The other authors declare no competing interests. This content is solely the responsibility of the authors and does not necessarily represent the official views of the US Department of Health and Human Services, Administration for Strategic Preparedness and Response.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}