{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:53:24Z","timestamp":1791914004502,"version":"4.3.4"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Hangzhou Municipal Medical and Health Science and Technology Project","award":["A20240835"],"award-info":[{"award-number":["A20240835"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Early-life antibiotic (ABX) exposure profoundly disrupts gut microbiota assembly, triggering long-lasting intestinal immune stress. While fecal microbiota transplantation (FMT) is a promising intervention, its immunological and ecological mechanisms in the juvenile gut remain underexplored. In this study, juvenile mice were subjected to a broad-spectrum ABX cocktail for 8 days followed by 4 days of adult-sourced FMT. 16S rRNA sequencing (n\u2009=\u20096\/group) revealed that ABX drastically altered the microbial landscape, causing a severe relative reduction of core commensals and an opportunistic expansion of Bacteroides. Subsequent molecular analyses on day 13 (n\u2009=\u20093\/group) demonstrated that this dysbiosis significantly upregulated the mucosal TLR4\/MyD88 signaling axis and effector cytokines IL-17 and IL-22. Strikingly, adult FMT administration effectively attenuated the TLR4 cascade and reduced pro-inflammatory cytokine transcript levels while immunoregulatory IL-10 transcripts remained partially elevated. Ecologically, FMT did not merely revert the gut to its naive juvenile baseline. Instead, it suppressed Bacteroides overgrowth and established a distinctly new, highly complex community enriched with putative mature, adult-signature taxa such as\n                    <jats:italic>Parabacteroides<\/jats:italic>\n                    ,\n                    <jats:italic>Tannerellaceae<\/jats:italic>\n                    , and\n                    <jats:italic>Desulfobacterota<\/jats:italic>\n                    . Interestingly, the downregulation of TLR4 occurred concurrently with the engraftment of these Gram-negative, LPS-bearing taxa. Collectively, adult-sourced FMT ameliorates ABX-induced immune stress not by restoring the original microbiota, but by driving the juvenile gut towards a putatively mature, structurally distinct, and potentially immunologically tolerant ecological state.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0359634","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:29:23Z","timestamp":1791912563000},"page":"e0359634","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adult-sourced fecal microbiota transplantation ameliorates early-life antibiotic-induced intestinal immune stress in juvenile mice associated with the modulation of the TLR4\/MyD88 signaling pathway"],"prefix":"10.1371","volume":"21","author":[{"given":"Xiang","family":"Qian","sequence":"first","affiliation":[{"name":"Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University","place":["Hangzhou, China"],"department":["Department of Clinical Laboratory"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjing","family":"Shen","sequence":"additional","affiliation":[{"name":"Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University","place":["Hangzhou, China"],"department":["Department of Clinical Laboratory"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianzhong","family":"Luo","sequence":"additional","affiliation":[{"name":"Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University","place":["Hangzhou, China"],"department":["Department of Clinical Laboratory"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University","place":["Hangzhou, China"],"department":["Department of Clinical Laboratory"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University","place":["Hangzhou, China"],"department":["Department of Clinical Laboratory"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hualin","family":"He","sequence":"additional","affiliation":[{"name":"Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University","place":["Hangzhou, China"],"department":["Department of Clinical Laboratory"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3397-1202","authenticated-orcid":true,"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University","place":["Hangzhou, China"],"department":["Department of Pediatrics"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"pone.0359634.ref001","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.mib.2020.05.011","article-title":"Neonatal gut microbiome and immunity","volume":"56","author":"KZ Sanidad","year":"2020","journal-title":"Curr Opin Microbiol"},{"issue":"1","key":"pone.0359634.ref002","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.03335-20","article-title":"An antibiotic-impacted microbiota compromises the development of colonic regulatory T cells and predisposes to dysregulated immune responses","volume":"12","author":"X Zhang","year":"2021","journal-title":"mBio"},{"issue":"3","key":"pone.0359634.ref003","doi-asserted-by":"crossref","first-page":"459","DOI":"10.3390\/jcm10030459","article-title":"The Association between early-life gut microbiota and long-term health and diseases","volume":"10","author":"A Sarkar","year":"2021","journal-title":"J Clin Med"},{"issue":"4","key":"pone.0359634.ref004","first-page":"74","article-title":"Prospects for the correction of intestinal microbiota in the prevention and treatment of asthma in children","volume":"90","author":"IV Ozerskaia","year":"2021","journal-title":"Vopr Pitan"},{"key":"pone.0359634.ref005","doi-asserted-by":"crossref","first-page":"1477882","DOI":"10.3389\/fmed.2024.1477882","article-title":"Gut dysbiosis mediates the association between antibiotic exposure and chronic disease","volume":"11","author":"F Guarner","year":"2024","journal-title":"Front Med (Lausanne)"},{"issue":"4","key":"pone.0359634.ref006","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1007\/s12602-023-10101-6","article-title":"Akkermansia muciniphila protects against antibiotic-associated diarrhea in mice","volume":"16","author":"S Liu","year":"2024","journal-title":"Probiotics Antimicrob Proteins"},{"issue":"12","key":"pone.0359634.ref007","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1007\/s13205-019-1967-2","article-title":"Bacterial diversity in intestinal mucosa of antibiotic-associated diarrhea mice","volume":"9","author":"G Xie","year":"2019","journal-title":"3 Biotech"},{"issue":"3","key":"pone.0359634.ref008","doi-asserted-by":"crossref","first-page":"237","DOI":"10.7861\/clinmedicine.18-3-237","article-title":"Clostridium difficile infection and antibiotic-associated diarrhoea","volume":"18","author":"BH Mullish","year":"2018","journal-title":"Clin Med (Lond)"},{"issue":"4","key":"pone.0359634.ref009","article-title":"Probiotics for the prevention of pediatric antibiotic-associated diarrhea","volume":"4","author":"Q Guo","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"key":"pone.0359634.ref010","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.phrs.2017.08.001","article-title":"Probiotics and antibiotic-associated diarrhea in children: A review and new evidence on Lactobacillus rhamnosus GG during and after antibiotic treatment","volume":"128","author":"C Mantegazza","year":"2018","journal-title":"Pharmacol Res"},{"issue":"3","key":"pone.0359634.ref011","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1097\/00004836-200603000-00017","article-title":"Probiotics for the prevention of antibiotic-associated diarrhea and Clostridium difficile diarrhea","volume":"40","author":"JA Katz","year":"2006","journal-title":"J Clin Gastroenterol"},{"issue":"8","key":"pone.0359634.ref012","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.3390\/biomedicines12081871","article-title":"The role of Fecal Microbiota Transplantation (FMT) in the management of metabolic diseases in humans: A narrative review","volume":"12","author":"E Zikou","year":"2024","journal-title":"Biomedicines"},{"issue":"1","key":"pone.0359634.ref013","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/s41522-023-00421-4","article-title":"Donor-recipient specificity and age-dependency in fecal microbiota therapy and probiotic resolution of gastrointestinal symptoms","volume":"9","author":"Q Wu","year":"2023","journal-title":"NPJ Biofilms Microbiomes"},{"issue":"3","key":"pone.0359634.ref014","doi-asserted-by":"crossref","first-page":"435","DOI":"10.14309\/ajg.0000000000002167","article-title":"Fecal microbiota transplantation across the lifespan: Balancing efficacy, safety, and innovation","volume":"118","author":"AS Gulati","year":"2023","journal-title":"Am J Gastroenterol"},{"issue":"1","key":"pone.0359634.ref015","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s40168-021-01165-z","article-title":"Intestinal microbiota shapes gut physiology and regulates enteric neurons and glia","volume":"9","author":"FA Vicentini","year":"2021","journal-title":"Microbiome"},{"issue":"32","key":"pone.0359634.ref016","doi-asserted-by":"crossref","first-page":"4574","DOI":"10.3748\/wjg.v28.i32.4574","article-title":"Wumei pills attenuates 5-fluorouracil-induced intestinal mucositis through Toll-like receptor 4\/myeloid differentiation factor 88\/nuclear factor-\u03baB pathway and microbiota regulation","volume":"28","author":"D-X Lu","year":"2022","journal-title":"World J Gastroenterol"},{"issue":"7","key":"pone.0359634.ref017","doi-asserted-by":"crossref","first-page":"935","DOI":"10.2174\/0115672018304338241003095955","article-title":"Fecal microbiota transplantation induced by wumei pills improves chemotherapy-induced intestinal mucositis in BALB\/c mice by modulating the TLR4\/MyD88\/NF-\u03baB signaling pathway","volume":"22","author":"D Lu","year":"2025","journal-title":"Curr Drug Deliv"},{"key":"pone.0359634.ref018","doi-asserted-by":"crossref","first-page":"1051962","DOI":"10.3389\/fcimb.2022.1051962","article-title":"Baihu renshen decoction ameliorates type 2 diabetes mellitus in rats through affecting gut microbiota enhancing gut permeability and inhibiting TLR4\/NF-\u03baB-mediated inflammatory response","volume":"12","author":"B Yao","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"issue":"4","key":"pone.0359634.ref019","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.immuni.2019.03.020","article-title":"IL-10 Family Cytokines IL-10 and IL-22: From basic science to clinical translation","volume":"50","author":"W Ouyang","year":"2019","journal-title":"Immunity"},{"key":"pone.0359634.ref020","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.3389\/fimmu.2020.01315","article-title":"IL-10 and IL-22 in mucosal immunity: Driving protection and pathology","volume":"11","author":"H-X Wei","year":"2020","journal-title":"Front Immunol"},{"issue":"6","key":"pone.0359634.ref021","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.cytogfr.2010.11.002","article-title":"The role of Th17 cytokines in primary mucosal immunity","volume":"21","author":"JK Kolls","year":"2010","journal-title":"Cytokine Growth Factor Rev"},{"issue":"6","key":"pone.0359634.ref022","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/ismej.2013.15","article-title":"Biphasic assembly of the murine intestinal microbiota during early development","volume":"7","author":"IG Pantoja-Feliciano","year":"2013","journal-title":"ISME J"},{"issue":"1","key":"pone.0359634.ref023","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1093\/femsre\/fuv036","article-title":"Heterogeneity of the gut microbiome in mice: guidelines for optimizing experimental design","volume":"40","author":"D Laukens","year":"2016","journal-title":"FEMS Microbiol Rev"},{"issue":"9","key":"pone.0359634.ref024","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/nbt.2676","article-title":"Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences","volume":"31","author":"MGI Langille","year":"2013","journal-title":"Nat Biotechnol"},{"issue":"4","key":"pone.0359634.ref025","doi-asserted-by":"crossref","first-page":"383","DOI":"10.4161\/gmic.21008","article-title":"Stabilization of the murine gut microbiome following weaning","volume":"3","author":"PD Schloss","year":"2012","journal-title":"Gut Microbes"},{"issue":"4","key":"pone.0359634.ref026","doi-asserted-by":"crossref","first-page":"289","DOI":"10.4161\/gmic.19897","article-title":"Microbial degradation of complex carbohydrates in the gut","volume":"3","author":"HJ Flint","year":"2012","journal-title":"Gut Microbes"},{"issue":"5","key":"pone.0359634.ref027","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors","volume":"11","author":"T Kawai","year":"2010","journal-title":"Nat Immunol"},{"key":"pone.0359634.ref028","doi-asserted-by":"crossref","first-page":"448","DOI":"10.3389\/fphys.2012.00448","article-title":"Microbial pathways in colonic sulfur metabolism and links with health and disease","volume":"3","author":"F Carbonero","year":"2012","journal-title":"Front Physiol"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0359634","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:29:28Z","timestamp":1791912568000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0359634"}},"subtitle":[],"editor":[{"given":"Adrian","family":"Ochoa-Leyva","sequence":"first","affiliation":[{"name":"Universidad Nacional Autonoma de Mexico Instituto de Biotecnologia","place":["MEXICO"]}],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,10,13]]},"references-count":28,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,10,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0359634","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,13]]}}}