{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T02:14:20Z","timestamp":1781576060402,"version":"3.54.5"},"reference-count":31,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Pediatric Surgery Clinic of the Medical University of Warsaw"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Necrotizing enterocolitis (NEC) is an inflammatory disease with an incidence of about one in 1000 live births, much higher in premature and low birth weight newborns. Intestinal dysbiosis is an important element in the pathogenesis of NEC, and for this reason, experimental models have been used to administer fecal microbiota transplants (FMTs) for prophylaxis and treatment of NEC with very satisfactory results. The primary endpoint of the study is safety, defined as the incidence of adverse events (AEs) and serious adverse events (SAEs) occurring from the time of intervention until hospital discharge, classified according to severity and assessed for relatedness to the intervention. Methods: This prospective, single-arm, open-label clinical study will include 20 infants born between 24 0\/7 and 36 6\/7 weeks of gestation. FMTs will be administered twice as a deep rectal infusion via a Foley catheter. The donors of the material from which the FMT will be prepared will be women in the third trimester of pregnancy. The safety of the therapy will be assessed by comparison with a control group, i.e., 20 patients who will meet the same inclusion criteria and will not meet any of the exclusion criteria, subject to the same hospital observation but without undergoing any medical\/therapeutic intervention other than the collection of biological material. Discussion: The study will provide data on the safety and initial efficacy of FMT in this group of patients, which will allow for further research into the use of this method in the prevention of infections and NEC. Ethics: The study protocol was approved by the Bioethics Committee of the Medical University of Warsaw, Warsaw, Poland (KB\/52\/2025). All procedures will follow the principles of the Declaration of Helsinki. The results of the study will be submitted for knowledge translation in peer-reviewed journals and presented at national and international pediatric society conferences. Clinical Trial Registration: The study is registered at ClinicalTrials.gov: ID: NCT06333405.<\/jats:p>","DOI":"10.3390\/ph19030437","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T11:06:52Z","timestamp":1773054412000},"page":"437","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Fecal Microbiota Transplantation (FMT) as a Prophylaxis of Necrotizing Enterocolitis (NEC)\u2014Protocol for a Safety Study"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1921-8133","authenticated-orcid":false,"given":"Ewa A.","family":"Bieganska","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0550-1915","authenticated-orcid":false,"given":"Marek","family":"Wolski","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Zarlenga","sequence":"additional","affiliation":[{"name":"Department of Neonatology and Rare Diseases, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8286-4512","authenticated-orcid":false,"given":"Jaroslaw","family":"Bilinski","sequence":"additional","affiliation":[{"name":"Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"},{"name":"Human Biome S.A. Gda\u0144sk, 02-234 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3812-7560","authenticated-orcid":false,"given":"Przemyslaw","family":"Kosinski","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Perinatology and Gynecology, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.earlhumdev.2016.03.008","article-title":"Etiology and medical management of NEC","volume":"97","author":"Gupta","year":"2016","journal-title":"Early Hum. Dev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/j.jamcollsurg.2014.11.026","article-title":"Serious congenital heart disease and necrotizing enterocolitis in very low birth weight neonates","volume":"220","author":"Fisher","year":"2015","journal-title":"J. Am. Coll. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/j.jpedsurg.2009.02.013","article-title":"Mortality of necrotizing enterocolitis expressed by birth weight categories","volume":"44","author":"Fitzgibbons","year":"2009","journal-title":"J. Pediatr. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1053\/j.sempedsurg.2008.02.005","article-title":"Neonatal necrotizing enterocolitis","volume":"17","author":"Henry","year":"2008","journal-title":"Semin. Pediatr. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mai, V., Torrazza, R.M., Ukhanova, M., Wang, X., Sun, Y., Li, N., Shuster, J., Sharma, R., Hudak, M.L., and Neu, J. (2013). Distortions in development of intestinal microbiota associated with late onset sepsis in preterm infants. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0052876"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"F456","DOI":"10.1136\/fetalneonatal-2011-301373","article-title":"Gut microbial colonisation in premature neonates predicts neonatal sepsis","volume":"97","author":"Madan","year":"2012","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s40168-017-0248-8","article-title":"Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis: A systematic review and meta-analysis","volume":"5","author":"Pammi","year":"2017","journal-title":"Microbiome"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1056\/NEJMra1005408","article-title":"Necrotizing enterocolitis","volume":"364","author":"Neu","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e224","DOI":"10.1093\/cid\/ciaa1635","article-title":"Profound Pathogen-Specific Alterations in Intestinal Microbiota Composition Precede Late-Onset Sepsis in Preterm Infants: A Longitudinal, Multicenter, Case-Control Study","volume":"73","author":"Niemarkt","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Brehin, C., Dubois, D., Dicky, O., Breinig, S., Oswald, E., and Serino, M. (2020). Evolution of Gut Microbiome and Metabolome in Suspected Necrotizing Enterocolitis: A Case-Control Study. J. Clin. Med., 9.","DOI":"10.3390\/jcm9072278"},{"key":"ref_11","first-page":"Cd002971","article-title":"Formula versus donor breast milk for feeding preterm or low birth weight infants","volume":"7","author":"Quigley","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Murphy, K., Ross, R.P., Ryan, C.A., Dempsey, E.M., and Stanton, C. (2021). Probiotics, Prebiotics, and Synbiotics for the Prevention of Necrotizing Enterocolitis. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.667188"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kurath-Koller, S., Neumann, C., Moissl-Eichinger, C., Kraschl, R., Kanduth, C., Hopfer, B., Pausan, M.R., Urlesberger, B., and Resch, B. (2020). Hospital Regimens Including Probiotics Guide the Individual Development of the Gut Microbiome of Very Low Birth Weight Infants in the First Two Weeks of Life. Nutrients, 12.","DOI":"10.3390\/nu12051256"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e032617","DOI":"10.1136\/bmjopen-2019-032617","article-title":"Efficacy of Bifidobacterium longum, B. infantis and Lactobacillus acidophilus probiotics to prevent gut dysbiosis in preterm infants of 28+0-32+6 weeks of gestation: A randomised, placebo-controlled, double-blind, multicentre trial: The PRIMAL Clinical Study protocol","volume":"9","author":"Meyer","year":"2019","journal-title":"BMJ Open"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1097\/MPG.0b013e3181adaee0","article-title":"Enteral nutrient supply for preterm infants: Commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition","volume":"50","author":"Agostoni","year":"2010","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1097\/MPG.0000000000001897","article-title":"Probiotics for Preterm Infants: A Strain-Specific Systematic Review and Network Meta-analysis","volume":"67","author":"Szajewska","year":"2018","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1097\/MPG.0000000000002655","article-title":"Probiotics and Preterm Infants: A Position Paper by the European Society for Paediatric Gastroenterology Hepatology and Nutrition Committee on Nutrition and the European Society for Paediatric Gastroenterology Hepatology and Nutrition Working Group for Probiotics and Prebiotics","volume":"70","author":"Shamir","year":"2020","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e20200706","DOI":"10.1542\/peds.2020-0706","article-title":"Effects of Probiotics in Preterm Infants: A Network Meta-analysis","volume":"147","author":"Chi","year":"2021","journal-title":"Pediatrics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1016\/j.jpedsurg.2018.10.045","article-title":"The protective effects of fecal microbiota transplantation in an experimental model of necrotizing enterocolitis","volume":"54","author":"Prado","year":"2019","journal-title":"J. Pediatr. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1016\/j.jpedsurg.2020.02.035","article-title":"Fecal microbiota transplantation by enema reduces intestinal injury in experimental necrotizing enterocolitis","volume":"55","author":"Liu","year":"2020","journal-title":"J. Pediatr. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.freeradbiomed.2017.03.011","article-title":"Fecal microbiota transplantation (FMT) could reverse the severity of experimental necrotizing enterocolitis (NEC) via oxidative stress modulation","volume":"108","author":"Li","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/s41522-022-00310-2","article-title":"Donor-dependent fecal microbiota transplantation efficacy against necrotizing enterocolitis in preterm pigs","volume":"8","author":"Hui","year":"2022","journal-title":"NPJ Biofilms Microbiomes"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1038\/s41467-020-15545-w","article-title":"Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity","volume":"11","author":"Kim","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1093\/cid\/ciaa948","article-title":"Disease Prevention Not Decolonization: A Model for Fecal Microbiota Transplantation in Patients Colonized With Multidrug-resistant Organisms","volume":"72","author":"Ghani","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Innes, A.J., Mullish, B.H., Ghani, R., Szydlo, R.M., Apperley, J.F., Olavarria, E., Palanicawandar, R., Kanfer, E.J., Milojkovic, D., and McDonald, J.A.K. (2021). Fecal Microbiota Transplant Mitigates Adverse Outcomes Seen in Patients Colonized With Multidrug-Resistant Organisms Undergoing Allogeneic Hematopoietic Cell Transplantation. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.684659"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Wu, H., Guo, K., Zhuo, Z., Zeng, R., Luo, Y., Yang, Q., Li, J., Jiang, R., Huang, Z., and Sha, W. (2022). Current therapy option for necrotizing enterocolitis: Practicalities and challenge. Front. Pediatr., 10.","DOI":"10.3389\/fped.2022.954735"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s00383-023-05476-0","article-title":"Necrotizing enterocolitis: Recent advances in treatment with translational potential","volume":"39","author":"Ganji","year":"2023","journal-title":"Pediatr. Surg. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/nur.20247","article-title":"Considerations in determining sample size for pilot studies","volume":"31","author":"Hertzog","year":"2008","journal-title":"Res. Nurs. Health"},{"key":"ref_29","unstructured":"Human Biome Institute (2026, January 18). FMT Preparations. Available online: https:\/\/human-biome.com\/en\/fmt-preparations\/."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"36","DOI":"10.18773\/austprescr.2020.014","article-title":"Faecal microbiota transplantation: Indications, evidence and safety","volume":"43","author":"Soo","year":"2020","journal-title":"Aust. Prescr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"E88","DOI":"10.1002\/ajh.26077","article-title":"Fecal microbiota transplantation in patients with acute and chronic graft-versus-host disease-spectrum of responses and safety profile. Results from a prospective, multicenter study","volume":"96","author":"Bilinski","year":"2021","journal-title":"Am. J. Hematol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/3\/437\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T11:11:30Z","timestamp":1773054690000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/3\/437"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,9]]},"references-count":31,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ph19030437"],"URL":"https:\/\/doi.org\/10.3390\/ph19030437","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,9]]}}}