{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:16:03Z","timestamp":1791231363517,"version":"4.1.0"},"reference-count":77,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T00:00:00Z","timestamp":1706054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004328","name":"Genentech","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>This study aimed to identify microbial drivers of inflammatory bowel disease [IBD], by investigating mucosal-associated bacteria and their detrimental products in IBD patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We directly cultured bacterial communities from mucosal biopsies from paediatric gastrointestinal patients and examined for pathogenicity-associated traits. Upon identifying Clostridium perfringens as toxigenic bacteria present in mucosal biopsies, we isolated strains and further characterized toxicity and prevalence.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Mucosal biopsy microbial composition differed from corresponding stool samples. C. perfringens was present in eight of nine patients\u2019 mucosal biopsies, correlating with haemolytic activity, but was not present in all corresponding stool samples. Large IBD datasets showed higher C. perfringens prevalence in stool samples of IBD adults [18.7\u201327.1%] versus healthy controls [5.1%]. In vitro, C. perfringens supernatants were toxic to cell types beneath the intestinal epithelial barrier, including endothelial cells, neuroblasts, and neutrophils, while the impact on epithelial cells was less pronounced, suggesting C. perfringens may be particularly damaging when barrier integrity is compromised. Further characterization using purified toxins and genetic insertion mutants confirmed perfringolysin O [PFO] toxin was sufficient for toxicity. Toxin RNA signatures were found in the original patient biopsies by PCR, suggesting intestinal production. C. perfringens supernatants also induced activation of neuroblast and dorsal root ganglion neurons in vitro, suggesting C. perfringens in inflamed mucosal tissue may directly contribute to abdominal pain, a frequent IBD symptom.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Gastrointestinal carriage of certain toxigenic C. perfringens may have an important pathogenic impact on IBD patients. These findings support routine monitoring of C. perfringens and PFO toxins and potential treatment in patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjae016","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T02:22:01Z","timestamp":1706149321000},"page":"985-1001","source":"Crossref","is-referenced-by-count":13,"title":["Toxigenic <i>Clostridium perfringens<\/i> Isolated from At-Risk Paediatric Inflammatory Bowel Disease Patients"],"prefix":"10.1093","volume":"18","author":[{"given":"James","family":"Kuo","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Host-Microbe Interactions, Genentech Inc. , South San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmina","family":"Uzunovic","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Genentech Inc. , South San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Department of Immunology Discovery, Genentech Inc. , South San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Dourado","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Genentech Inc. , South San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Gierke","sequence":"additional","affiliation":[{"name":"Department of Pathology, Genentech Inc. , South San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manohary","family":"Rajendram","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Host-Microbe Interactions, Genentech Inc. , South San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Keilberg","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Host-Microbe Interactions, Genentech Inc. , South San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Mar","sequence":"additional","affiliation":[{"name":"Department of Human Pathobiology and OMNI Reverse Translation, Genentech Inc. , South San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Stekol","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco Benioff Children\u2019s Hospital , San Francisco, CA, 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Curry","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco Benioff Children\u2019s Hospital , San Francisco, CA, 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Verstraete","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco Benioff Children\u2019s Hospital , San Francisco, CA, 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Lund","sequence":"additional","affiliation":[{"name":"Department of Microchemistry, Proteomics & Lipidomics, Genentech Inc. , South San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Microchemistry, Proteomics & Lipidomics, Genentech Inc. , South San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona B","family":"Tamburini","sequence":"additional","affiliation":[{"name":"Department of Human Pathobiology and OMNI Reverse Translation, Genentech Inc. , South San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie S","family":"Omattage","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Host-Microbe Interactions, Genentech Inc. , South San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Masureel","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Genentech Inc. , South San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven T","family":"Rutherford","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Host-Microbe Interactions, Genentech Inc. , South San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H","family":"Hackos","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Genentech Inc. , South San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man-Wah","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Host-Microbe Interactions, Genentech Inc. , South San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allyson L","family":"Byrd","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology, Genentech Inc. , South San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E","family":"Keir","sequence":"additional","affiliation":[{"name":"Department of Human Pathobiology and OMNI Reverse Translation, Genentech Inc. , South San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Skippington","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Host-Microbe Interactions, Genentech Inc. , South San Francisco, CA , USA"},{"name":"Department of Bioinformatics, Genentech Inc. , South San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2289-0214","authenticated-orcid":false,"given":"Kelly M","family":"Storek","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Host-Microbe Interactions, Genentech Inc. , South San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,1,24]]},"reference":[{"key":"2024080621455565000_CIT0001","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/S0140-6736(07)60750-8","article-title":"Inflammatory bowel disease: cause and immunobiology","volume":"369","author":"Baumgart","year":"2007","journal-title":"Lancet"},{"key":"2024080621455565000_CIT0002","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nrgastro.2015.186","article-title":"Immunopathogenesis of IBD: current state of the art","volume":"13","author":"Souza","year":"2016","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2024080621455565000_CIT0003","doi-asserted-by":"crossref","first-page":"801892","DOI":"10.3389\/fmicb.2022.801892","article-title":"Bacterial species associated with human inflammatory bowel disease and their pathogenic mechanisms","volume":"13","author":"Zhang","year":"2022","journal-title":"Front Microbiol"},{"key":"2024080621455565000_CIT0004","doi-asserted-by":"crossref","first-page":"G420","DOI":"10.1152\/ajpgi.00411.2017","article-title":"Inflammation-related differences in mucosa-associated microbiota and intestinal barrier function in colonic Crohn\u2019s disease","volume":"315","author":"Libertucci","year":"2018","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2024080621455565000_CIT0005","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/ibd.20848","article-title":"Pain and inflammatory bowel disease","volume":"15","author":"Bielefeldt","year":"2009","journal-title":"Inflamm Bowel Dis"},{"key":"2024080621455565000_CIT0006","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1038\/s41598-017-02835-5","article-title":"Comparison of non-invasive biomarkers faecal BAFF, calprotectin and FOBT in discriminating IBS from IBD and evaluation of intestinal inflammation","volume":"7","author":"Fu","year":"2017","journal-title":"Sci Rep"},{"key":"2024080621455565000_CIT0007","doi-asserted-by":"crossref","first-page":"e1002535","DOI":"10.1371\/journal.ppat.1002535","article-title":"Taste for blood: hemoglobin as a nutrient source for pathogens","volume":"8","author":"Pishchany","year":"2012","journal-title":"PLoS Pathog"},{"key":"2024080621455565000_CIT0008","doi-asserted-by":"crossref","first-page":"e1000949","DOI":"10.1371\/journal.ppat.1000949","article-title":"The battle for iron between bacterial pathogens and their vertebrate hosts","volume":"6","author":"Skaar","year":"2010","journal-title":"PLoS Pathog"},{"key":"2024080621455565000_CIT0009","doi-asserted-by":"crossref","first-page":"4170","DOI":"10.1016\/j.cell.2022.09.008","article-title":"Gut-innervating nociceptors regulate the intestinal microbiota to promote tissue protection","volume":"185","author":"Zhang","year":"2022","journal-title":"Cell"},{"key":"2024080621455565000_CIT0010","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41385-020-00368-1","article-title":"The intestinal neuro-immune axis: crosstalk between neurons, immune cells, and microbes","volume":"14","author":"Jacobson","year":"2021","journal-title":"Mucosal Immunol"},{"key":"2024080621455565000_CIT0011","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41467-017-02448-6","article-title":"Staphylococcus aureus produces pain through pore-forming toxins and neuronal TRPV1 that is silenced by QX-314","volume":"9","author":"Blake","year":"2018","journal-title":"Nat Commun"},{"key":"2024080621455565000_CIT0012","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/j.cell.2018.04.006","article-title":"Blocking neuronal signaling to immune cells treats streptococcal invasive infection","volume":"173","author":"Pinho-Ribeiro","year":"2018","journal-title":"Cell"},{"key":"2024080621455565000_CIT0013","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1080\/21505594.2021.1886777","article-title":"Pathogenicity and virulence of Clostridium perfringens","volume":"12","author":"Gohari","year":"2021","journal-title":"Virulence"},{"key":"2024080621455565000_CIT0014","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41426-018-0144-8","article-title":"An update on the human and animal enteric pathogen Clostridium perfringens","volume":"7","author":"Kiu","year":"2018","journal-title":"Emerg Microbes Infect"},{"key":"2024080621455565000_CIT0015","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1038\/s41564-023-01385-z","article-title":"Particular genomic and virulence traits associated with preterm infant-derived toxigenic Clostridium perfringens strains","volume":"8","author":"Kiu","year":"2023","journal-title":"Nat Microbiol"},{"key":"2024080621455565000_CIT0016","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.crohns.2013.08.018","article-title":"Enterotoxigenic Clostridium perfringens infection and pediatric patients with inflammatory bowel disease","volume":"8","author":"Banaszkiewicz","year":"2014","journal-title":"J Crohns Colitis"},{"key":"2024080621455565000_CIT0017","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1136\/gutjnl-2015-309398","article-title":"Specific members of the predominant gut microbiota predict pouchitis following colectomy and IPAA in UC","volume":"66","author":"Machiels","year":"2017","journal-title":"Gut"},{"key":"2024080621455565000_CIT0018","doi-asserted-by":"crossref","first-page":"8929","DOI":"10.3748\/wjg.v22.i40.8929","article-title":"Fecal microbiota in pouchitis and ulcerative colitis","volume":"22","author":"Li","year":"2016","journal-title":"World J Gastroenterol"},{"key":"2024080621455565000_CIT0019","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1053\/j.gastro.2019.10.001","article-title":"Predominantly antibiotic-resistant intestinal Microbiome persists in patients with pouchitis who respond to antibiotic therapy","volume":"158","author":"Dubinsky","year":"2020","journal-title":"Gastroenterology"},{"key":"2024080621455565000_CIT0020","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s11894-018-0623-z","article-title":"Therapeutic drug monitoring in pediatric inflammatory bowel disease","volume":"20","author":"Carman","year":"2018","journal-title":"Curr Gastroenterol Rep"},{"key":"2024080621455565000_CIT0021","doi-asserted-by":"crossref","first-page":"4382","DOI":"10.1128\/AEM.67.9.4382-4384.2001","article-title":"Rapid confirmation of Clostridium perfringens by using chromogenic and fluorogenic substrates","volume":"67","author":"Adcock","year":"2001","journal-title":"Appl Environ Microbiol"},{"key":"2024080621455565000_CIT0022","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.mimet.2009.10.018","article-title":"The ClosTron: mutagenesis in Clostridium refined and streamlined","volume":"80","author":"Heap","year":"2010","journal-title":"J Microbiol Methods"},{"key":"2024080621455565000_CIT0023","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.cell.2021.12.035","article-title":"Genetic manipulation of gut microbes enables single-gene interrogation in a complex microbiome","volume":"185","author":"Jin","year":"2022","journal-title":"Cell"},{"key":"2024080621455565000_CIT0024","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1038\/ismej.2012.8","article-title":"Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms","volume":"6","author":"Caporaso","year":"2012","journal-title":"ISME J"},{"key":"2024080621455565000_CIT0025","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s40168-023-01486-1","article-title":"IL-22 alters gut microbiota composition and function to increase aryl hydrocarbon receptor activity in mice and humans","volume":"11","author":"Mar","year":"2023","journal-title":"Microbiome"},{"key":"2024080621455565000_CIT0026","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":"Bolyen","year":"2019","journal-title":"Nat Biotechnol"},{"key":"2024080621455565000_CIT0027","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1136\/gutjnl-2022-328387","article-title":"Dose escalation randomised study of efmarodocokin alfa in healthy volunteers and patients with ulcerative colitis","volume":"72","author":"Wagner","year":"2023","journal-title":"Gut"},{"key":"2024080621455565000_CIT0028","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/s41587-020-0501-8","article-title":"A complete domain-to-species taxonomy for Bacteria and Archaea","volume":"38","author":"Parks","year":"2020","journal-title":"Nat Biotechnol"},{"key":"2024080621455565000_CIT0029","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/nbt.4229","article-title":"A standardized bacterial taxonomy based on genome phylogeny substantially revises the tree of life","volume":"36","author":"Parks","year":"2018","journal-title":"Nat Biotechnol"},{"key":"2024080621455565000_CIT0030","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.stem.2018.11.016","article-title":"Human intestinal organoids maintain self-renewal capacity and cellular diversity in niche-inspired culture condition","volume":"23","author":"Fujii","year":"2018","journal-title":"Cell stem cell"},{"key":"2024080621455565000_CIT0031","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/s41467-023-36014-0","article-title":"Cross-species transcriptomic atlas of dorsal root ganglia reveals species-specific programs for sensory function","volume":"14","author":"Jung","year":"2023","journal-title":"Nat Commun"},{"key":"2024080621455565000_CIT0032","doi-asserted-by":"crossref","first-page":"e20200606","DOI":"10.1084\/jem.20200606","article-title":"Gut microbiome stability and dynamics in healthy donors and patients with non-gastrointestinal cancers","volume":"218","author":"Byrd","year":"2020","journal-title":"J Exp Med"},{"key":"2024080621455565000_CIT0033","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.cell.2015.11.001","article-title":"Personalized nutrition by prediction of glycemic responses","volume":"163","author":"Zeevi","year":"2015","journal-title":"Cell"},{"key":"2024080621455565000_CIT0034","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S2468-1253(22)00303-X","article-title":"Etrolizumab as induction and maintenance therapy in patients with moderately to severely active Crohn\u2019s disease (BERGAMOT): a randomised, placebo-controlled, double-blind, phase 3 trial","volume":"8","author":"Sandborn","year":"2023","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"2024080621455565000_CIT0035","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/S2468-1253(21)00295-8","article-title":"Etrolizumab for maintenance therapy in patients with moderately to severely active ulcerative colitis (LAUREL): a randomised, placebo-controlled, double-blind, phase 3 study","volume":"7","author":"Vermeire","year":"2022","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"2024080621455565000_CIT0036","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S2468-1253(21)00338-1","article-title":"Etrolizumab versus adalimumab or placebo as induction therapy for moderately to severely active ulcerative colitis (HIBISCUS): two phase 3 randomised, controlled trials","volume":"7","author":"Rubin","year":"2022","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"2024080621455565000_CIT0037","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1038\/nmeth.4468","article-title":"Accessible, curated metagenomic data through ExperimentHub","volume":"14","author":"Pasolli","year":"2017","journal-title":"Nat Methods"},{"key":"2024080621455565000_CIT0038","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1016\/j.cell.2020.05.001","article-title":"Personalized mapping of drug metabolism by the human gut microbiome","volume":"181","author":"Javdan","year":"2019","journal-title":"Cell"},{"key":"2024080621455565000_CIT0039","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1186\/s12876-021-01975-3","article-title":"Comparison of sampling methods in assessing the microbiome from patients with ulcerative colitis","volume":"21","author":"Kim","year":"2021","journal-title":"BMC Gastroenterol"},{"key":"2024080621455565000_CIT0040","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.chom.2014.02.005","article-title":"The treatment-naive microbiome in new-onset Crohn\u2019s disease","volume":"15","author":"Gevers","year":"2014","journal-title":"Cell Host Microbe"},{"key":"2024080621455565000_CIT0041","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1080\/19490976.2014.1000080","article-title":"Inferred metagenomic comparison of mucosal and fecal microbiota from individuals undergoing routine screening colonoscopy reveals similar differences observed during active inflammation","volume":"6","author":"Tang","year":"2015","journal-title":"Gut Microbes"},{"key":"2024080621455565000_CIT0042","doi-asserted-by":"crossref","first-page":"D912","DOI":"10.1093\/nar\/gkab1107","article-title":"VFDB 2022: a general classification scheme for bacterial virulence factors","volume":"50","author":"Liu","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"2024080621455565000_CIT0043","doi-asserted-by":"crossref","first-page":"D325","DOI":"10.1093\/nar\/gki008","article-title":"VFDB: a reference database for bacterial virulence factors","volume":"33","author":"Chen","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"2024080621455565000_CIT0044","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.3389\/fmicb.2020.02065","article-title":"Pathogenicity factors of genomic islands in intestinal and extraintestinal Escherichia coli","volume":"11","author":"Desvaux","year":"2020","journal-title":"Front Microbiol"},{"key":"2024080621455565000_CIT0045","doi-asserted-by":"crossref","first-page":"649953","DOI":"10.3389\/fmicb.2021.649953","article-title":"Comparative genomics of Clostridium perfringens reveals patterns of host-associated phylogenetic clades and virulence factors","volume":"12","author":"Geier","year":"2021","journal-title":"Front Microbiol"},{"key":"2024080621455565000_CIT0046","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.clim.2014.12.004","article-title":"The Milieu Int\u00e9rieur study \u2014 An integrative approach for study of human immunological variance","volume":"157","author":"Thomas","year":"2015","journal-title":"Clin Immunol"},{"key":"2024080621455565000_CIT0047","doi-asserted-by":"crossref","first-page":"7792","DOI":"10.1038\/s41598-019-44281-5","article-title":"Prevalence and characterization of Clostridium perfringens toxinotypes among patients with antibiotic-associated diarrhea in Iran","volume":"9","author":"Azimirad","year":"2019","journal-title":"Sci Rep"},{"key":"2024080621455565000_CIT0048","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.anaerobe.2018.04.011","article-title":"Expansion of the Clostridium perfringens toxin-based typing scheme","volume":"53","author":"Rood","year":"2018","journal-title":"Anaerobe"},{"key":"2024080621455565000_CIT0049","doi-asserted-by":"crossref","first-page":"777","DOI":"10.3389\/fmicb.2019.00777","article-title":"Large-scale genomic analyses and toxinotyping of Clostridium perfringens implicated in foodborne outbreaks in France","volume":"10","author":"Abdelrahim","year":"2019","journal-title":"Front Microbiol"},{"key":"2024080621455565000_CIT0050","doi-asserted-by":"crossref","first-page":"713509","DOI":"10.3389\/fmicb.2021.713509","article-title":"Pathogenic characterization of Clostridium perfringens strains isolated from patients with massive intravascular hemolysis","volume":"12","author":"Suzaki","year":"2021","journal-title":"Front Microbiol"},{"key":"2024080621455565000_CIT0051","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.plasmid.2007.04.002","article-title":"Disruption of a toxin gene by introduction of a foreign gene into the chromosome of Clostridium perfringens using targetron-induced mutagenesis","volume":"58","author":"Chen","year":"2007","journal-title":"Plasmid"},{"key":"2024080621455565000_CIT0052","article-title":"A versatile human intestinal organoid-derived epithelial monolayer model for the study of enteric pathogens","volume":"19","author":"Nickerson","year":"2021","journal-title":"Microbiol Spectr"},{"key":"2024080621455565000_CIT0053","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/s41586-019-1291-3","article-title":"Mapping human microbiome drug metabolism by gut bacteria and their genes","volume":"570","author":"Zimmermann","year":"2019","journal-title":"Nature"},{"key":"2024080621455565000_CIT0054","doi-asserted-by":"crossref","first-page":"001154","DOI":"10.1099\/mic.0.001154","article-title":"Bacterial pore-forming toxins","volume":"168","author":"Ulhuq","year":"2022","journal-title":"Microbiology (Reading)"},{"key":"2024080621455565000_CIT0055","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nri3661","article-title":"Cytokines in inflammatory bowel disease","volume":"14","author":"Neurath","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"2024080621455565000_CIT0056","doi-asserted-by":"crossref","first-page":"8577","DOI":"10.1523\/JNEUROSCI.2812-04.2004","article-title":"ATP-induced non-neuronal cell permeabilization in the rat inner retina","volume":"24","author":"Innocenti","year":"2004","journal-title":"J Neurosci"},{"key":"2024080621455565000_CIT0057","doi-asserted-by":"crossref","first-page":"8497","DOI":"10.1073\/pnas.1018550108","article-title":"Activity-dependent targeting of TRPV1 with a pore-permeating capsaicin analog","volume":"108","author":"Li","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024080621455565000_CIT0058","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1089\/fpd.2012.1316","article-title":"Epidemiology of foodborne disease outbreaks caused by Clostridium perfringens, United States, 1998\u20132010","volume":"10","author":"Grass","year":"2013","journal-title":"Foodborne Pathog Dis"},{"key":"2024080621455565000_CIT0059","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1097\/QCO.0b013e32832a8a5d","article-title":"Commensal bacteria, traditional and opportunistic pathogens, dysbiosis and bacterial killing in inflammatory bowel diseases","volume":"22","author":"Packey","year":"2009","journal-title":"Curr Opin Infect Dis"},{"key":"2024080621455565000_CIT0060","doi-asserted-by":"crossref","first-page":"4561","DOI":"10.1128\/AEM.00177-06","article-title":"Further comparison of temperature effects on growth and survival of Clostridium perfringens type A isolates carrying a chromosomal or plasmid-borne enterotoxin gene","volume":"72","author":"Li","year":"2006","journal-title":"Appl Environ Microbiol"},{"key":"2024080621455565000_CIT0061","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.pop.2017.07.010","article-title":"An update on inflammatory bowel disease","volume":"44","author":"Sairenji","year":"2017","journal-title":"Prim Care"},{"key":"2024080621455565000_CIT0062","doi-asserted-by":"crossref","first-page":"3919","DOI":"10.1128\/JB.01455-08","article-title":"Virulence gene regulation by the agr system in Clostridium perfringens","volume":"191","author":"Ohtani","year":"2009","journal-title":"J Bacteriol"},{"key":"2024080621455565000_CIT0063","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1128\/JB.02614-14","article-title":"Structure-function analysis of peptide signaling in the Clostridium perfringens Agr-like quorum sensing system","volume":"197","author":"Ma","year":"2015","journal-title":"J Bacteriol"},{"key":"2024080621455565000_CIT0064","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.jbiosc.2017.12.019","article-title":"Metabolic dependent and independent pH-drop shuts down VirSR quorum sensing in Clostridium perfringens","volume":"125","author":"Adachi","year":"2018","journal-title":"J Biosci Bioeng"},{"key":"2024080621455565000_CIT0065","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.3390\/cells11111734","article-title":"Making sense of quorum sensing at the intestinal mucosal interface","volume":"11","author":"Uhlig","year":"2022","journal-title":"Cells"},{"key":"2024080621455565000_CIT0066","doi-asserted-by":"crossref","first-page":"e0016","DOI":"10.1097\/IN9.0000000000000016","article-title":"Revisiting the \u201cstarved gut\u201d hypothesis in inflammatory bowel disease","volume":"5","author":"Colgan","year":"2023","journal-title":"Immunometabolism"},{"key":"2024080621455565000_CIT0067","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/s41419-019-2086-z","article-title":"Keep calm: the intestinal barrier at the interface of peace and war","volume":"10","author":"Thoo","year":"2019","journal-title":"Cell Death Dis"},{"key":"2024080621455565000_CIT0068","doi-asserted-by":"crossref","first-page":"7904","DOI":"10.1128\/IAI.69.12.7904-7910.2001","article-title":"Synergistic effects of alpha-toxin and perfringolysin O in Clostridium perfringens-mediated gas gangrene","volume":"69","author":"Awad","year":"2001","journal-title":"Infect Immun"},{"key":"2024080621455565000_CIT0069","doi-asserted-by":"crossref","first-page":"3125","DOI":"10.1038\/ncomms4125","article-title":"TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins","volume":"5","author":"Meseguer","year":"2014","journal-title":"Nat Commun"},{"key":"2024080621455565000_CIT0070","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/nature12479","article-title":"Bacteria activate sensory neurons that modulate pain and inflammation","volume":"501","author":"Chiu","year":"2013","journal-title":"Nature"},{"key":"2024080621455565000_CIT0071","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nature11234","article-title":"Structure, function and diversity of the healthy human microbiome","volume":"486","author":"Huttenhower","year":"2012","journal-title":"Nature"},{"key":"2024080621455565000_CIT0072","doi-asserted-by":"crossref","first-page":"105818","DOI":"10.1016\/j.mimet.2019.105818","article-title":"Evaluation of methods for DNA extraction from Clostridium tyrobutyricum spores and its detection by qPCR","volume":"169","author":"Esteban","year":"2020","journal-title":"J Microbiol Methods"},{"key":"2024080621455565000_CIT0073","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s00284-016-1123-8","article-title":"Physical pre-treatment improves efficient DNA extraction and qPCR sensitivity from Clostridium difficile spores in faecal swine specimens","volume":"73","author":"Grze\u015bkowiak","year":"2016","journal-title":"Curr Microbiol"},{"key":"2024080621455565000_CIT0074","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1186\/1471-2334-13-459","article-title":"Prevalence of Clostridium difficile colonization among healthcare workers","volume":"13","author":"Friedman","year":"2013","journal-title":"BMC Infect Dis"},{"key":"2024080621455565000_CIT0075","doi-asserted-by":"crossref","first-page":"7577","DOI":"10.3748\/wjg.v19.i43.7577","article-title":"Clostridium difficile and inflammatory bowel disease: role in pathogenesis and implications in treatment","volume":"19","author":"Nitzan","year":"2013","journal-title":"World J Gastroenterol"},{"key":"2024080621455565000_CIT0076","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.crohns.2011.09.005","article-title":"Clostridium difficile infection is associated with worse long term outcome in patients with ulcerative colitis","volume":"6","author":"Navaneethan","year":"2012","journal-title":"J Crohns Colitis"},{"key":"2024080621455565000_CIT0077","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1093\/ecco-jcc\/jjz006","article-title":"Enterotoxigenic Clostridium perfringens infection as an adverse event after faecal microbiota transplantation in two patients with ulcerative colitis and recurrent Clostridium difficile infection: a neglected agent in donor screening","volume":"13","author":"Azimirad","year":"2019","journal-title":"J Crohns Colitis"}],"container-title":["Journal of Crohn's and Colitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/advance-article-pdf\/doi\/10.1093\/ecco-jcc\/jjae016\/56752970\/jjae016.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article-pdf\/18\/7\/985\/58747698\/jjae016.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article-pdf\/18\/7\/985\/58747698\/jjae016.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T04:08:19Z","timestamp":1723003699000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article\/18\/7\/985\/7588639"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,24]]},"references-count":77,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,1,24]]},"published-print":{"date-parts":[[2024,8,6]]}},"URL":"https:\/\/doi.org\/10.1093\/ecco-jcc\/jjae016","relation":{},"ISSN":["1873-9946","1876-4479"],"issn-type":[{"value":"1873-9946","type":"print"},{"value":"1876-4479","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,7]]},"published":{"date-parts":[[2024,1,24]]}}}