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The classical sign of NE is the foul smell gas in the ballooned small intestine. We hypothesized that deoxycholic acid (DCA) reduced NE by inhibiting C. perfringens virulence signaling pathways. To evaluate the hypothesis, C. perfringens strains CP1 and wild-type (WT) HN13 and its mutants were cultured with different bile acids, including DCA and isoallolithocholic acid (isoalloLCA). Growth, hydrogen sulfide (H2S) production, and virulence gene expression were measured. Notably, isoalloLCA was more potent in reducing growth, H2S production, and virulence gene expression in CP1 and WT HN13 compared to DCA, while other bile acids were less potent compared to DCA. Interestingly, there was a slightly different impact between DCA and isoalloLCA on the growth, H2S production, and virulence gene expression in the three HN13 mutants, suggesting possibly different signaling pathways modulated by the two bile acids. In conclusion, DCA and isoalloLCA reduced C. perfringens virulence by transcriptionally modulating the pathogen signaling pathways. The findings could be used to design new strategies to prevent and treat C. perfringens-induced diseases.<\/jats:p>","DOI":"10.3390\/pathogens12101202","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T01:42:12Z","timestamp":1695865332000},"page":"1202","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Potent Bile Acid Microbial Metabolites Modulate Clostridium perfringens Virulence"],"prefix":"10.3390","volume":"12","author":[{"given":"Tahrir","family":"Alenezi","sequence":"first","affiliation":[{"name":"Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA"},{"name":"Cell and Molecular Biology, University of Arkansas, Fayetteville, AR 72701, USA"},{"name":"College of Medical Applied Sciences, The Northern Border University, Arar 91431, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Fu","sequence":"additional","affiliation":[{"name":"Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bilal","family":"Alrubaye","sequence":"additional","affiliation":[{"name":"Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thamer","family":"Alanazi","sequence":"additional","affiliation":[{"name":"Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA"},{"name":"Cell and Molecular Biology, University of Arkansas, Fayetteville, AR 72701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayidh","family":"Almansour","sequence":"additional","affiliation":[{"name":"Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA"},{"name":"Cell and Molecular Biology, University of Arkansas, Fayetteville, AR 72701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA"},{"name":"Cell and Molecular Biology, University of Arkansas, Fayetteville, AR 72701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5601-0812","authenticated-orcid":false,"given":"Xiaolun","family":"Sun","sequence":"additional","affiliation":[{"name":"Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA"},{"name":"Cell and Molecular Biology, University of Arkansas, Fayetteville, AR 72701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"387","DOI":"10.3390\/immuno2020024","article-title":"Clostridium perfringens-Induced Necrotic Diseases: An Overview","volume":"2","author":"Fu","year":"2022","journal-title":"Immuno"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1080\/03079457.2016.1158781","article-title":"NetB and necrotic enteritis: The hole movable story","volume":"45","author":"Rood","year":"2016","journal-title":"Avian Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1080\/03079457.2016.1163521","article-title":"Epidemiologic aspects of necrotic enteritis in broiler chickens - disease occurrence and production performance","volume":"45","author":"Kaldhusdal","year":"2016","journal-title":"Avian Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1080\/03079450500112195","article-title":"Intercurrent coccidiosis and necrotic enteritis of chickens: Rational, integrated disease management by maintenance of gut integrity","volume":"34","author":"Williams","year":"2005","journal-title":"Avian Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3389\/fvets.2018.00199","article-title":"Evaluation of the Epithelial Barrier Function and Ileal Microbiome in an Established Necrotic Enteritis Challenge Model in Broiler Chickens","volume":"5","author":"Latorre","year":"2018","journal-title":"Front. 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