{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T21:13:40Z","timestamp":1789161220896,"version":"build-2803163510"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,2,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Antibiotic-associated diarrhea (AAD) is a self-limiting disorder triggered by antibiotic therapy in pediatric populations. Although multiple probiotics are clinically employed for AAD management, the therapeutic efficacy of\n                      <jats:italic toggle=\"yes\">Clostridium butyricum<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">C. butyricum<\/jats:italic>\n                      ) in pediatric AAD and its underlying mechanisms remain poorly characterized. This study aimed to establish a juvenile mice model of AAD and investigate the therapeutic potential of oral\n                      <jats:italic toggle=\"yes\">C. butyricum<\/jats:italic>\n                      administration in juvenile mice subjected to continuous antibiotics exposure. We systematically assessed pathological changes in colonic tissue, colitis severity, intestinal epithelial barrier integrity, fecal metabolomic profiles, and gut microbiota diversity. Our analysis demonstrates that\n                      <jats:italic toggle=\"yes\">C. butyricum<\/jats:italic>\n                      ameliorates intestinal inflammation, enhances barrier function by modulating the gut microbiota and its metabolites, and significantly alleviates diarrhea symptoms in juvenile AAD mice. Collectively, these findings indicate that the therapeutic benefits of\n                      <jats:italic toggle=\"yes\">C. butyricum<\/jats:italic>\n                      are closely linked to its ability to tolerate continuous antibiotic exposure, providing a scientific rationale for its co-administration with antibiotics.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Clostridium butyricum<\/jats:italic>\n                        demonstrates significant therapeutic potential for pediatric antibiotic-associated diarrhea (AAD) by dual modulation of gut microbiota and host physiology. This study reveals its capacity to alleviate intestinal inflammation, restore barrier integrity via upregulation of tight junction proteins and mucins, and rebalance gut microbiota linked to key anti-inflammatory metabolites\u2014even under ongoing antibiotic exposure. These findings position\n                        <jats:italic toggle=\"yes\">C. butyricum<\/jats:italic>\n                        as a targeted probiotic therapy for AAD, offering mechanistic insights to advance microbiome-driven interventions for antibiotic-induced diarrhea in children.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01976-25","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T14:00:59Z","timestamp":1767794459000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["<i>Clostridium butyricum<\/i>\n                    RH2 ameliorates diarrhea in juvenile mice under continuous antibiotic exposure by modulating gut microbiota and metabolome"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3753-8381","authenticated-orcid":false,"given":"Yufeng","family":"Zhao","sequence":"first","affiliation":[{"name":"Hangzhou Grand Biologic Pharmaceutical Inc.","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan","family":"Gao","sequence":"additional","affiliation":[{"name":"Hangzhou Grand Biologic Pharmaceutical Inc.","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Shang","sequence":"additional","affiliation":[{"name":"Hangzhou Grand Biologic Pharmaceutical Inc.","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Hangzhou Grand Biologic Pharmaceutical Inc.","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianlei","family":"Ren","sequence":"additional","affiliation":[{"name":"Hangzhou Grand Biologic Pharmaceutical Inc.","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyu","family":"Guo","sequence":"additional","affiliation":[{"name":"Hangzhou Grand Biologic Pharmaceutical Inc.","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5568-5425","authenticated-orcid":false,"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Hangzhou Grand Biologic Pharmaceutical Inc.","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.2217\/17460913.3.5.563"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gtc.2021.02.010"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2020.1843396"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i11.3078"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1153070"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000001081"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2014.66"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s15006-021-9762-5"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD004827.pub5"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctim.2017.07.001"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13404"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13344"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2536"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1079\/BJNBJN2002563"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2015.10.014"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1442-200x.2003.01671.x"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.12.4.571"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.9.2.173"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14153599"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu13020365"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8111650"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29672-z"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2020.154409"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1066053"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-019-0692-y"},{"key":"e_1_3_5_27_2","first-page":"24","article-title":"The role of butyric acid as a protective agent against inflammatory bowel diseases","volume":"9","author":"Tralongo P","year":"2014","unstructured":"Tralongo P, Tomasello G, Sinagra E, Damiani P, Leone A, Palumbo VD, Giammanco M, Di Majo D, Damiani F, Abruzzo A, Bruno A, Cassata G, Cicero L, Noto M, Tomasello R, Lo Monte AI. 2014. The role of butyric acid as a protective agent against inflammatory bowel diseases. EuroMediterranean Biomed J 9:24\u201335.","journal-title":"EuroMediterranean Biomed J"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2023.113528"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells10071775"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/nutrit\/nuw067"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2021.152126"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells12141888"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms3040641"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29857"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01331"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1021\/jf505050c"}],"container-title":["Microbiology Spectrum"],"original-title":[],"contributor":[{"given":"Sahar M. Jawad","family":"Abduladheem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"reviewer"}]}],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.01976-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.01976-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:49:14Z","timestamp":1788223754000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.01976-25"}},"subtitle":[],"editor":[{"given":"Yuan Pin","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,2,3]]},"references-count":35,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2,3]]}},"alternative-id":["10.1128\/spectrum.01976-25"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.01976-25","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,3]]},"assertion":[{"value":"2025-07-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01976-25"}}