{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T21:35:21Z","timestamp":1787866521290,"version":"build-2784847793"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014063","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000}}],"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/01450"],"award-info":[{"award-number":["PI20\/01450"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014849","name":"Conselleria de Cultura, Educaci\u00f3n y Ciencia, Generalitat Valenciana","doi-asserted-by":"publisher","award":["CIAICO\/2023\/274"],"award-info":[{"award-number":["CIAICO\/2023\/274"]}],"id":[{"id":"10.13039\/501100014849","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Instituto de Investigacion Sanitaria y Biom\u00e9dica de Alicante - ISABIAL","award":["2024\/B\/29"],"award-info":[{"award-number":["2024\/B\/29"]}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PTA2021-020215-I"],"award-info":[{"award-number":["PTA2021-020215-I"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Alterations in the gut microbiome are central to the pathogenesis and recurrence of\n                      <jats:italic>Clostridioides difficile<\/jats:italic>\n                      infection (CDI).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate intestinal microbiome changes during CDI and their association with recurrence, sex, age, and immunosuppression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients from the CDI-ANCRAID-SEICV cohort were consecutively enrolled. Stool samples were obtained at diagnosis (Dx), end of treatment (ET), and eight weeks post-treatment (8W) or upon recurrence. Microbiota composition was analyzed by 16S rRNA sequencing using QIIME2 and R. Outcomes were compared by demographics, immunosuppression, and treatment (vancomycin [VNC], vancomycin-bezlotuzumab [VNC-BZL], fidaxomicin [FDX]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 143 patients, non-recurrent cases showed higher biodiversity at 8W versus diagnosis (H p\u2009=\u20090.002, ASVs p\u2009&lt;\u20090.001), unlike recurrent cases. Diversity decreased with VNC (H p\u2009&gt;\u20090.001, ASVs p\u2009&lt;\u20090.001) but was preserved with FDX (H p\u2009=\u20090.15). Recovery of Shannon diversity was limited in women (p\u2009=\u20090.50) and immunocompromised patients (p\u2009=\u20090.31). At ET,\n                      <jats:italic>Fusobacteria<\/jats:italic>\n                      and\n                      <jats:italic>Verrucomicrobiota<\/jats:italic>\n                      were less abundant in recurrent than non-recurrent cases (0.77%, 0.53% vs 3.43%, 3.50%). FDX-treated samples showed higher\n                      <jats:italic>Bacteroidetes<\/jats:italic>\n                      (31.33%) compared to VNC (5.23%) or VNC-BZL (3.12%). Women exhibited increased\n                      <jats:italic>Firmicutes<\/jats:italic>\n                      abundance (p\u2009=\u20090.034).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Restoration of microbial diversity correlates with CDI resolution. FDX preserves gut microbiota better than VNC or VNC-BZL. Women and immunocompromised patients demonstrate impaired microbiota recovery.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.ppat.1014063","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T17:24:52Z","timestamp":1775496292000},"page":"e1014063","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dynamics of the microbiota in patients with Clostridioides difficile: Recurrence, treatment, sex, and immunosuppression"],"prefix":"10.1371","volume":"22","author":[{"given":"Maria Paz","family":"Ventero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocio","family":"Herrero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iryna","family":"Tyshkovska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Dolores","family":"Valverde-Fredet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8007-5739","authenticated-orcid":true,"given":"Juan Carlos","family":"Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Rodr\u00edguez-Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Gonz\u00e1lez-De-La-Aleja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Trigo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Parra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana-Isabel","family":"Aller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Otero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinaldo","family":"Espindola-Gomez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Manuel","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva M.","family":"Le\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel Nicolas","family":"Navarrete-Lorite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jara","family":"Llenas-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Portillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Jover","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Tasias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Jose","family":"Caston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concepci\u00f3n","family":"Gil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Vinuesa-Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Gomez-Ayerbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Mart\u00ednez Marcos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Merchante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esperanza Merino","family":"De Lucas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"ppat.1014063.ref001","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.mib.2020.01.016","article-title":"Microbe-microbe interactions during Clostridioides difficile infection","volume":"53","author":"A Abbas","year":"2020","journal-title":"Curr Opin Microbiol"},{"key":"ppat.1014063.ref002","article-title":"Clostridioides difficile infection: history, epidemiology, risk factors, prevention, clinical manifestations, treatment, and future options","author":"SD Bella","year":"2024","journal-title":"Clinical Microbiology Reviews"},{"issue":"7","key":"ppat.1014063.ref003","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.3390\/microorganisms11071738","article-title":"Clostridioides difficile in pigs and dairy cattle in Northern Italy: prevalence, characterization and comparison between animal and human strains","volume":"11","author":"P Spigaglia","year":"2023","journal-title":"Microorganisms"},{"issue":"10","key":"ppat.1014063.ref004","doi-asserted-by":"crossref","first-page":"774","DOI":"10.3390\/diagnostics10100774","article-title":"Potential trends of point-of-care diagnostics-the next generation of the laboratory diagnosis","volume":"10","author":"S-W Lin","year":"2020","journal-title":"Diagnostics (Basel)"},{"key":"ppat.1014063.ref005","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.mib.2021.11.002","article-title":"Computational approaches to understanding Clostridioides difficile metabolism and virulence","volume":"65","author":"ML Jenior","year":"2022","journal-title":"Curr Opin Microbiol"},{"key":"ppat.1014063.ref006","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1111\/imj.15520","article-title":"The gut microbiota and gut disease","volume":"51","author":"SR Fehily","year":"2021","journal-title":"Intern Med J"},{"issue":"9","key":"ppat.1014063.ref007","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.tim.2020.03.004","article-title":"A revised understanding of clostridioides difficile spore germination","volume":"28","author":"AJ Lawler","year":"2020","journal-title":"Trends Microbiol"},{"issue":"1","key":"ppat.1014063.ref008","doi-asserted-by":"crossref","first-page":"1979882","DOI":"10.1080\/19490976.2021.1979882","article-title":"Pathobionts: mechanisms of survival, expansion, and interaction with host with a focus on Clostridioides difficile","volume":"13","author":"H Chandra","year":"2021","journal-title":"Gut Microbes"},{"issue":"3","key":"ppat.1014063.ref009","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3390\/jpm15030094","article-title":"Insights into the interaction between Clostridioides difficile and the gut microbiome","volume":"15","author":"D Mougiou","year":"2025","journal-title":"J Pers Med"},{"issue":"1","key":"ppat.1014063.ref010","doi-asserted-by":"crossref","first-page":"2505269","DOI":"10.1080\/19490976.2025.2505269","article-title":"Metagenomic analysis reveals distinct patterns of gut microbiota features with diversified functions in C. difficile infection (CDI), asymptomatic carriage and non-CDI diarrhea","volume":"17","author":"L Wang","year":"2025","journal-title":"Gut Microbes"},{"issue":"1","key":"ppat.1014063.ref011","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13073-016-0298-8","article-title":"Dynamics of the fecal microbiome in patients with recurrent and nonrecurrent Clostridium difficile infection","volume":"8","author":"AM Seekatz","year":"2016","journal-title":"Genome Med"},{"key":"ppat.1014063.ref012","doi-asserted-by":"crossref","DOI":"10.1177\/17562848241253089","article-title":"Microbiota restoration therapies for recurrent Clostridioides difficile infection reach an important new milestone","volume":"17","author":"HL DuPont","year":"2024","journal-title":"Ther Adv Gastroenterol"},{"issue":"1","key":"ppat.1014063.ref013","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1186\/s12879-024-09506-7","article-title":"Fecal microbiota composition is a better predictor of recurrent Clostridioides difficile infection than clinical factors in a prospective, multicentre cohort study","volume":"24","author":"TM van Rossen","year":"2024","journal-title":"BMC Infect Dis"},{"issue":"4","key":"ppat.1014063.ref014","doi-asserted-by":"crossref","first-page":"268","DOI":"10.36519\/idcm.2024.380","article-title":"Clostridioides difficile infections and factors associated with recurrence","volume":"6","author":"S \u00c7etin","year":"2024","journal-title":"Infect Dis Clin Microbiol"},{"issue":"8","key":"ppat.1014063.ref015","doi-asserted-by":"crossref","first-page":"646","DOI":"10.3390\/pathogens13080646","article-title":"Clostridioides difficile and gut microbiota: from colonization to infection and treatment","volume":"13","author":"P Spigaglia","year":"2024","journal-title":"Pathogens"},{"issue":"32","key":"ppat.1014063.ref016","doi-asserted-by":"crossref","DOI":"10.1097\/MD.0000000000039213","article-title":"Efficacy of fidaxomicin versus vancomycin in the treatment of Clostridium difficile infection: a systematic meta-analysis","volume":"103","author":"Z Zhao","year":"2024","journal-title":"Medicine (Baltimore)"},{"key":"ppat.1014063.ref017","doi-asserted-by":"crossref","first-page":"101151","DOI":"10.1016\/j.lanepe.2024.101151","article-title":"Comparative effectiveness of different therapies for Clostridioides difficile infection in adults: a systematic review and network meta-analysis of randomized controlled trials","volume":"49","author":"DS Bedn\u00e1rik","year":"2025","journal-title":"Lancet Reg Health Eur"},{"issue":"10","key":"ppat.1014063.ref018","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.01347-24","article-title":"Gut microbiome and plasma lipidome analysis reveals a specific impact of Clostridioides difficile infection on intestinal bacterial communities and sterol metabolism","volume":"15","author":"R Arcay","year":"2024","journal-title":"mBio"},{"issue":"11","key":"ppat.1014063.ref019","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1016\/j.jiph.2021.09.016","article-title":"Risk factors for recurrence of Clostridioides difficile in hospitalized patients","volume":"14","author":"D Alrahmany","year":"2021","journal-title":"J Infect Public Health"},{"issue":"6","key":"ppat.1014063.ref020","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1093\/cid\/ciad792","article-title":"A randomized, double-blind, phase 3 safety and efficacy study of ridinilazole versus vancomycin for treatment of Clostridioides difficile infection: clinical outcomes with microbiome and metabolome correlates of response","volume":"78","author":"PC Okhuysen","year":"2024","journal-title":"Clin Infect Dis"},{"key":"ppat.1014063.ref021","doi-asserted-by":"crossref","DOI":"10.1093\/cid\/cis338","article-title":"Fidaxomicin preserves the intestinal microbiome during and after treatment of Clostridium difficile infection (CDI) and reduces both toxin reexpression and recurrence of CDI","volume":"55","author":"TJ Louie","year":"2012","journal-title":"Clin Infect Dis"},{"issue":"6","key":"ppat.1014063.ref022","doi-asserted-by":"crossref","first-page":"106306","DOI":"10.1016\/j.jinf.2024.106306","article-title":"Recurrent Clostridioides difficile infections in solid organ transplant recipients: the international CALIPSO study","volume":"89","author":"G Tiseo","year":"2024","journal-title":"J Infect"},{"issue":"2","key":"ppat.1014063.ref023","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1093\/cid\/ciad606","article-title":"An open-label, randomized trial comparing fidaxomicin with oral vancomycin for the treatment of Clostridioides difficile Infection in hospitalized patients receiving concomitant antibiotics for concurrent infections","volume":"78","author":"K Rao","year":"2024","journal-title":"Clin Infect Dis"},{"issue":"10","key":"ppat.1014063.ref024","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.3390\/antibiotics11101365","article-title":"Fidaxomicin for the treatment of Clostridioides difficile infection in adult patients: an update on results from randomized controlled trials","volume":"11","author":"DR Giacobbe","year":"2022","journal-title":"Antibiotics (Basel)"},{"issue":"2","key":"ppat.1014063.ref025","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1053\/j.gastro.2020.09.057","article-title":"The healthy microbiome\u2014what is the definition of a healthy gut microbiome?","volume":"160","author":"F Shanahan","year":"2021","journal-title":"Gastroenterology"},{"key":"ppat.1014063.ref026","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.ijid.2019.10.028","article-title":"Clostridioides difficile infection in immunocompromised hospitalized patients is associated with a high recurrence rate","volume":"90","author":"T Avni","year":"2020","journal-title":"Int J Infect Dis"},{"key":"ppat.1014063.ref027","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ijid.2024.01.002","article-title":"Clostridioides difficile infections, recurrences, and clinical outcomes in real-world settings from 2015 to 2019: The RECUR England study","volume":"140","author":"S Ghosh","year":"2024","journal-title":"Int J Infect Dis"},{"issue":"7","key":"ppat.1014063.ref028","doi-asserted-by":"crossref","DOI":"10.1093\/cid\/ciy149","article-title":"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)","volume":"66","author":"LC McDonald","year":"2018","journal-title":"Clin Infect Dis"},{"key":"ppat.1014063.ref029","doi-asserted-by":"crossref","DOI":"10.1016\/j.cmi.2021.09.038","article-title":"European Society of Clinical Microbiology and Infectious Diseases: 2021 Update on the Treatment Guidance Document for Clostridioides Difficile Infection in Adults","volume":"27","author":"J van Prehn","year":"2021","journal-title":"Clin Microbiol Infect"},{"issue":"5","key":"ppat.1014063.ref030","doi-asserted-by":"crossref","DOI":"10.1093\/cid\/ciab718","article-title":"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","volume":"73","author":"S Johnson","year":"2021","journal-title":"Clin Infect Dis"},{"issue":"1","key":"ppat.1014063.ref031","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s40121-025-01261-9","article-title":"Clinical impact of implementing a specific clinical pathway for the management of Clostridioides difficile Infection","volume":"15","author":"M Rodr\u00edguez-Fern\u00e1ndez","year":"2026","journal-title":"Infect Dis Ther"},{"key":"ppat.1014063.ref032","doi-asserted-by":"crossref","first-page":"103208","DOI":"10.1016\/j.jbi.2019.103208","article-title":"The REDCap Consortium: Building an International Community of Software Platform Partners","volume":"95","author":"PA Harris","year":"2019","journal-title":"J Biomed Inform"},{"key":"ppat.1014063.ref033","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jbi.2008.08.010","article-title":"Research electronic data capture (REDCap)\u2014a metadata-driven methodology and workflow process for providing translational research informatics support","volume":"42","author":"PA Harris","year":"2009","journal-title":"J Biomed Inform"},{"key":"ppat.1014063.ref034","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2","volume":"37","author":"E Bolyen","year":"2019","journal-title":"Nat Biotechnol"},{"issue":"1","key":"ppat.1014063.ref035","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gks808","article-title":"Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies","volume":"41","author":"A Klindworth","year":"2013","journal-title":"Nucleic Acids Res"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1014063","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014063","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T17:51:59Z","timestamp":1776361919000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014063"}},"subtitle":[],"editor":[{"given":"William","family":"Navarre","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,4,6]]},"references-count":35,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1014063","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,6]]}}}