{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:04:14Z","timestamp":1789646654532,"version":"4.0.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gastrointestinal infections are the leading cause of death for pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Conventional microbiological testing (CMT) often fails to identify the pathogens, resulting in delayed diagnosis and poor treatment outcomes. Metagenomic next-generation sequencing (mNGS) offers a promising method that does not require cultivation, but its application in this specific situation has not been fully studied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>185 fecal samples were collected from 96 children who underwent HSCT and suffered from diarrhea. All samples were simultaneously subjected to mNGS and CMT testing. The diagnostic performance, pathogen spectrum and prevalence of gastrointestinal infection pathogens were systematically analyzed and compared.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with CMT, mNGS detected significantly more bacteria, viruses and atypical pathogens. Among the pathogens detected by mNGS in the 185 fecal samples, the predominant bacteria were\n                      <jats:italic>Pseudomonas<\/jats:italic>\n                      spp. (28 cases),\n                      <jats:italic>Clostridioides<\/jats:italic>\n                      spp. (28 cases),\n                      <jats:italic>Campylobacter<\/jats:italic>\n                      spp. (25 cases),\n                      <jats:italic>Acinetobacter<\/jats:italic>\n                      spp. (16 cases), and\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      (13 cases).\n                      <jats:italic>Clostridioides<\/jats:italic>\n                      spp. exhibited a significantly higher detection rate in fecal samples from patients receiving CsA-based combination therapy (p=0.01099) and those with bone marrow from unrelated donors (p=0.03188).\n                      <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                      (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.03038) and\n                      <jats:italic>Campylobacter<\/jats:italic>\n                      spp.(\n                      <jats:italic>p<\/jats:italic>\n                      = 0.00549) were detected significantly more frequently in patients within the early phase (1\u201330 days). The detection rate of\n                      <jats:italic>Adenovirus<\/jats:italic>\n                      was markedly decreased during the intermediate phase (31\u2013100 days) (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.01458). Furthermore,\n                      <jats:italic>Polyomavirus<\/jats:italic>\n                      showed a significantly increased detection rate in patients with short-term diarrhea (1\u20133 days) (\n                      <jats:italic>p=<\/jats:italic>\n                      0.03451).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings highlight the substantial superiority of mNGS over CMT in pathogen detection, with a broader coverage encompassing bacteria, viruses, and atypical organisms. It uncovers complex polymicrobial and viral-bacterial co-infections, delineates infection dynamics linked to immune reconstitution. Integrating mNGS into the diagnostic workflow holds great potential for enabling precision antimicrobial therapy and improving outcomes in this high-risk population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1868295","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:15:37Z","timestamp":1788412537000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Application of metagenomic next-generation sequencing in gastrointestinal infections in children after allogeneic hematopoietic stem cell transplantation"],"prefix":"10.3389","volume":"16","author":[{"given":"Zhenghao","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Children\u2019s Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunzhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Children\u2019s Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Children\u2019s Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangzheng","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Children\u2019s Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Children\u2019s Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifeng","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Children\u2019s Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Children\u2019s Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Children\u2019s Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1017\/s095026889800106x","article-title":"Pseudomonas aeruginosa as a cause of infectious diarrhoea","volume":"121","author":"Adlard","year":"1998","journal-title":"Epidemiol. Infect."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.713631","article-title":"Novel insights into the mechanism of GVHD-induced tissue damage","volume":"12","author":"Ara","year":"2021","journal-title":"Front. Immunol."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.4084\/MJHID.2015.045","article-title":"Bacterial infections in hematopoietic stem cell transplant recipients","volume":"7","author":"Balletto","year":"2015","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.23736\/S0026-4946.18.04991-5","article-title":"MW polyomavirus in diarrheal Italian infants","author":"Bergallo","year":"2018","journal-title":"Minerva Pediatrica"},{"key":"B5","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1128\/JCM.02674-14","article-title":"Multicenter evaluation of the BioFire FilmArray gastrointestinal panel for etiologic diagnosis of infectious gastroenteritis","volume":"53","author":"Buss","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1080\/14712598.2021.1872541","article-title":"The role of microbiota in allogeneic hematopoietic stem cell transplantation","volume":"21","author":"Chang","year":"2021","journal-title":"Expert Opin. Biol. Ther."},{"key":"B7","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1182\/blood-2011-12-401166","article-title":"Graft-versus-host disease disrupts intestinal microbial ecology by inhibiting Paneth cell production of \u03b1-defensins","volume":"120","author":"Eriguchi","year":"2012","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2023.2221821","article-title":"Altered intestinal microbiome and epithelial damage aggravate intestinal graft-versus-host disease","volume":"15","author":"Gao","year":"2023","journal-title":"Gut Microbes"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01888-15","article-title":"Making the leap from research laboratory to clinic: Challenges and opportunities for next-generation sequencing in infectious disease diagnostics","volume":"6","author":"Goldberg","year":"2015","journal-title":"mBio"},{"key":"B10","doi-asserted-by":"publisher","first-page":"3838","DOI":"10.1128\/JCM.00407-06","article-title":"Shiga toxin 2-producing Acinetobacter haemolyticus associated with a case of bloody diarrhea","volume":"44","author":"Grotiuz","year":"2006","journal-title":"J. Clin. Microbiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/s41591-020-1105-z","article-title":"Rapid pathogen detection by metagenomic next-generation sequencing of infected body fluids","volume":"27","author":"Gu","year":"2021","journal-title":"Nat. Med."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049449","article-title":"Discovery of a novel polyomavirus in acute diarrheal samples from children","volume":"7","author":"Guixia","year":"2012","journal-title":"PLoS One"},{"key":"B13","doi-asserted-by":"publisher","first-page":"34","DOI":"10.7748\/ns.31.39.34.s39","article-title":"Cancer in children and young people","volume":"31","author":"Haidrani","year":"2017","journal-title":"Nurs. Standard: Off. Newspaper R. Coll. Nurs."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1002\/9781118063842.ch10","article-title":"Predominant Staphylococcus aureus isolated from antibiotic-associated diarrhea is clinically relevant and produces enterotoxin A and the bicomponent toxin LukE-LukD","volume":"55","author":"Huang","year":"2017","journal-title":"J. Clin. Microbiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"765","DOI":"10.17265\/2328-2150\/2018.08.007","article-title":"Hematopoietic stem cell transplantation in Vietnam: Current status and future directions","volume":"6","author":"Huynh","year":"2018","journal-title":"J. Pharm. Pharmacol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1186\/s12879-022-07284-8","article-title":"Comparison and development of a metagenomic next-generation sequencing protocol for combined detection of DNA and RNA pathogens in cerebrospinal fluid","volume":"22","author":"Jiang","year":"2022","journal-title":"BMC Infect. Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"742","DOI":"10.3346\/jkms.2001.16.6.742","article-title":"Pseudomonas aeruginosa as a potential cause of antibiotic-associated diarrhea","volume":"16","author":"Kim","year":"2002","journal-title":"J. Korean Med. Sci."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/med\/9780199204854.003.07060702_update_001","article-title":"Interconnections of Pseudomonas aeruginosa quorum-sensing systems in intestinal permeability and inflammation","volume":"13","author":"Koh","year":"2018","journal-title":"PloS One"},{"key":"B19","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"B20","doi-asserted-by":"publisher","first-page":"3107","DOI":"10.1128\/JCM.01324-13","article-title":"Prevalence of 10 human polyomaviruses in fecal samples from children with acute gastroenteritis: a case-control study","volume":"51","author":"Li","year":"2013","journal-title":"J. Clin. Microbiol."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.1018938","article-title":"Diagnostic efficiency of metagenomic next-generation sequencing for suspected spinal tuberculosis in China: A multicenter prospective study","volume":"13","author":"Li","year":"2022","journal-title":"Front. Microbiol."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.987692","article-title":"Rapid diagnosis of Talaromyces marneffei infection by metagenomic next-generation sequencing technology in a Chinese cohort of inborn errors of immunity","volume":"12","author":"Liu","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1101\/gr.238170.118","article-title":"Laboratory validation of a clinical metagenomic sequencing assay for pathogen detection in cerebrospinal fluid","volume":"29","author":"Miller","year":"2019","journal-title":"Genome Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.medcli.2018.07.012","article-title":"Graft-versus-host disease. Enfermedad del injerto contra el receptor","volume":"152","author":"Moreno","year":"2019","journal-title":"Med. Clin. (Barc)"},{"key":"B25","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.bbmt.2018.09.031","article-title":"Characteristics of late fatal infections after allogeneic hematopoietic cell transplantation","volume":"25","author":"Norkin","year":"2019","journal-title":"Biol. Blood Marrow Transplant."},{"key":"B26","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1080\/00365540110027097","article-title":"Fecal carriage of vancomycin- and ampicillin-resistant enterococci observed in swedish adult patients with diarrhea but not among healthy subjects","volume":"33","author":"Olofsson","year":"2001","journal-title":"Scandinavian J. Infect. Diseases"},{"key":"B27","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1007\/s42770-019-00166-3","article-title":"Human polyomaviruses 10 and 11 in faecal samples from brazilian children","volume":"51","author":"Pinheiro","year":"2019","journal-title":"Braz. J. Microbiol."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.596175","article-title":"Metagenomic next-generation sequencing of cerebrospinal fluid for the diagnosis of external ventricular and lumbar drainage-associated ventriculitis and meningitis","volume":"11","author":"Qian","year":"2020","journal-title":"Front. Microbiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.jiac.2016.05.006","article-title":"An overview of infectious complications after allogeneic hematopoietic stem cell transplantation","volume":"22","author":"Sahin","year":"2016","journal-title":"J. Infect. Chemother."},{"key":"B30","doi-asserted-by":"publisher","first-page":"S268","DOI":"10.1016\/j.jtct.2025.01.408","article-title":"Haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide for children with non-malignant disease","volume":"31","author":"Sakaguchi","year":"2025","journal-title":"Transplant. Cell. Ther."},{"key":"B31","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1016\/j.bbmt.2018.12.753","article-title":"Incidence of adenovirus infection in hematopoietic stem cell transplantation recipients: Findings from the AdVance study","volume":"25","author":"Sedl\u00e1ek","year":"2019","journal-title":"Biol. Blood Marrow Transplantation: J. Am. Soc. For. Blood Marrow Transplant."},{"key":"B32","doi-asserted-by":"publisher","first-page":"i","DOI":"10.1038\/nmeth.f.395","article-title":"Advances in flavivirus research applications: New techniques using the FastPrep-24 5G sample preparation system","volume":"13","author":"Whyte","year":"2016","journal-title":"Nat. Methods"},{"key":"B33","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1186\/s13059-019-1891-0","article-title":"Improved metagenomic analysis with Kraken 2","volume":"20","author":"Wood","year":"2019","journal-title":"Genome Biol."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-023-00790-5","article-title":"Utilizing metagenomic next-generation sequencing (mNGS) for rapid pathogen identification and to inform clinical decision-making: Results from a large real-world cohort","author":"Xu","year":"2023","journal-title":"Infect. Dis. Ther"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.811492","article-title":"Application of metagenomic next-generation sequencing in the etiological diagnosis of infective endocarditis during the perioperative period of cardiac surgery: A prospective cohort study","volume":"9","author":"Zeng","year":"2022","journal-title":"Front. Cardiovasc. Med."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1868295\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:39:22Z","timestamp":1789645162000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1868295\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":35,"alternative-id":["10.3389\/fcimb.2026.1868295"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1868295","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]},"article-number":"1868295"}}