{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T01:47:24Z","timestamp":1789091244968,"version":"build-2803163510"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T00:00:00Z","timestamp":1643241600000},"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. Nutr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The use of probiotics has been considered as a new intervention for ventilator-associated pneumonia (VAP) prevention in the intensive care unit (ICU). The aim of this meta-analysis was to evaluate the effect of probiotics on mechanical-ventilated patients in ICU.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PubMed, Embase, Scopus, and the Cochrane Library were searched for relevant randomized controlled trials (RCTs) from their respective inception through October 10, 2021. All studies meeting the inclusion criteria were selected to evaluate the effect of probiotics on patients receiving mechanical ventilation in ICU.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 15 studies involving 4,693 participants met our inclusion criterion and were included in this meta-analysis. The incidence of VAP in the probiotic group was significantly lower (odds ratio [<jats:italic>OR<\/jats:italic>] 0.58, 95% <jats:italic>CI<\/jats:italic> 0.41 to 0.81; <jats:italic>p<\/jats:italic> = 0.002; <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> = 71%). However, a publication bias may be present as the test of asymmetry was significant (<jats:italic>p<\/jats:italic> = 0.007). The probiotic administration was associated with a significant reduction in the duration of mechanical ventilation (mean difference [<jats:italic>MD<\/jats:italic>] \u22121.57, 95% <jats:italic>CI<\/jats:italic> \u22123.12 to \u22120.03; <jats:italic>p<\/jats:italic> = 0.05; inconsistency [<jats:italic>I<\/jats:italic>]<jats:sup>2<\/jats:sup> = 80%), length of ICU stay (MD \u22121.87, 95% <jats:italic>CI<\/jats:italic> \u22123.45 to \u22120.28; <jats:italic>p<\/jats:italic> = 0.02; <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> = 76%), and incidence of bacterial colonization (<jats:italic>OR<\/jats:italic> 0.59, 95% <jats:italic>CI<\/jats:italic> 0.45 to 0.78; <jats:italic>p<\/jats:italic> = 0.0001; <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> = 34%). Moreover, no statistically significant differences were observed regarding the incidence of diarrhea (<jats:italic>OR<\/jats:italic> 0.90, 95% <jats:italic>CI<\/jats:italic> 0.65 to 1.25; <jats:italic>p<\/jats:italic> = 0.54; <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> = 12%) and mortality (<jats:italic>OR<\/jats:italic> 0.91, 95% <jats:italic>CI<\/jats:italic> 0.80 to 1.05; <jats:italic>p<\/jats:italic> = 0.19; <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> = 0%) between probiotics group and control group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our meta-analysis shows that probiotics are associated with a reduction in VAP, as well as the duration of mechanical ventilation, ICU length of stay, and bacterial colonization, but no significant effects on ICU mortality and occurrence of diarrhea. However, in consideration of the significant heterogeneity and publication bias, our findings need to be further validated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Systematic Review Registration<\/jats:title><jats:p><jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/<\/jats:ext-link>, identifier: CRD42020150770.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2021.798827","type":"journal-article","created":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T15:17:05Z","timestamp":1643296625000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Clinical Benefits From Administering Probiotics to Mechanical Ventilated Patients in Intensive Care Unit: A PRISMA-Guided Meta-Analysis"],"prefix":"10.3389","volume":"8","author":[{"given":"Hongzhuan","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqing","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiujie","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaping","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhong","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.ajic.2008.03.002","article-title":"CDC\/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting","volume":"36","author":"Horan","year":"2008","journal-title":"Am J Infect Control."},{"key":"B2","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1007\/s00134-020-05980-0","article-title":"Ventilator-associated pneumonia in adults: a narrative review","volume":"46","author":"Papazian","year":"2020","journal-title":"Intensive Care Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2184","DOI":"10.1097\/01.CCM.0000181731.53912.D9","article-title":"Clinical and economic consequences of ventilator-associated pneumonia: a systematic review","volume":"33","author":"Safdar","year":"2005","journal-title":"Crit Care Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1016\/S1473-3099(13)70081-1","article-title":"Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies","volume":"13","author":"Melsen","year":"2013","journal-title":"Lancet Infect Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1378\/chest.13-0853","article-title":"The clinical impact and preventability of ventilator-associated conditions in critically ill patients who are mechanically ventilated","volume":"144","author":"Muscedere","year":"2013","journal-title":"Chest."},{"key":"B6","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1080\/14787210.2017.1250625","article-title":"Challenges and opportunities in the treatment of ventilator-associated pneumonia","volume":"15","author":"Schreiber","year":"2017","journal-title":"Expert Rev Anti Infect Ther."},{"key":"B7","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1038\/nrgastro.2014.66","article-title":"Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic","volume":"11","author":"Hill","year":"2014","journal-title":"Nat Rev Gastroenterol Hepatol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.2165\/11538080-000000000-00000","article-title":"Diagnosis, management and prevention of ventilator-associated pneumonia: an update","volume":"70","author":"Vincent","year":"2010","journal-title":"Drugs."},{"key":"B9","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1136\/gut.2003.034249","article-title":"Probiotics in inflammatory bowel disease: is it all gut flora modulation?","volume":"53","author":"Ghosh","year":"2004","journal-title":"Gut."},{"key":"B10","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/s40560-020-00487-8","article-title":"Efficacy of probiotics in the prevention of VAP in critically ill ICU patients: an updated systematic review and meta-analysis of randomized control trials","volume":"8","author":"Batra","year":"2020","journal-title":"J Intensive Care."},{"key":"B11","doi-asserted-by":"publisher","first-page":"673","DOI":"10.4187\/respcare.07097","article-title":"Probiotics for the prevention of ventilator-associated pneumonia: a meta-analysis of randomized controlled trials","volume":"65","author":"Su","year":"2020","journal-title":"Respir Care."},{"key":"B12","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1177\/1060028020983021","article-title":"Preventive effect of probiotics on ventilator-associated pneumonia: a meta-analysis of 2428 patients","volume":"55","author":"Ji","year":"2021","journal-title":"Ann Pharmacother."},{"key":"B13","doi-asserted-by":"publisher","first-page":"00302","DOI":"10.1183\/23120541.00302-2020","article-title":"Do probiotics help prevent ventilator-associated pneumonia in critically ill patients? A systematic review with meta-analysis","volume":"7","author":"Zhao","year":"2021","journal-title":"ERJ Open Res"},{"key":"B14","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/s12876-016-0552-y","article-title":"Liver abscess and bacteremia caused by lactobacillus: role of probiotics? Case report and review of the literature","volume":"16","author":"Sherid","year":"2016","journal-title":"BMC Gastroenterol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"S129","DOI":"10.1093\/cid\/civ085","article-title":"Risk and safety of probiotics","volume":"60","author":"Doron","year":"2015","journal-title":"Clin Infect Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1001\/jama.2021.13355","article-title":"Effect of probiotics on incident ventilator-associated pneumonia in critically ill patients: a randomized clinical trial","volume":"326","author":"Johnstone","year":"2021","journal-title":"JAMA."},{"key":"B17","doi-asserted-by":"publisher","first-page":"b2700","DOI":"10.1136\/bmj.b2700","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration","volume":"339","author":"Liberati","year":"2009","journal-title":"BMJ."},{"key":"B18","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1002\/ncp.10191","article-title":"Effect of a probiotic preparation on ventilator-associated pneumonia in critically ill patients admitted to the intensive care unit: a prospective double-blind randomized controlled trial","volume":"34","author":"Mahmoodpoor","year":"2019","journal-title":"Nutr Clin Pract."},{"key":"B19","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1186\/s13054-018-2209-4","article-title":"Can probiotics be an alternative to chlorhexidine for oral care in the mechanically ventilated patient? A multicentre, prospective, randomised controlled open trial","volume":"22","author":"Klarin","year":"2018","journal-title":"Crit Care."},{"key":"B20","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1186\/s13054-018-2167-x","article-title":"Synbiotics modulate gut microbiota and reduce enteritis and ventilator-associated pneumonia in patients with sepsis: a randomized controlled trial","volume":"22","author":"Shimizu","year":"2018","journal-title":"Crit Care."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1007\/s00134-016-4303-x","article-title":"Effect of probiotics on the incidence of ventilator-associated pneumonia in critically ill patients: a randomized controlled multicenter trial","volume":"42","author":"Zeng","year":"2016","journal-title":"Intensive Care Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1007\/s00134-015-3694-4","article-title":"Probiotic prophylaxis to prevent ventilator associated pneumonia (VAP) in children on mechanical ventilation: an open-label randomized controlled trial","volume":"41","author":"Banupriya","year":"2015","journal-title":"Intensive Care Med."},{"key":"B23","first-page":"253","article-title":"Randomized controlled study of probiotics containing Lactobacillus casei (Shirota strain) for prevention of ventilator-associated pneumonia","volume":"98","author":"Rongrungruang","year":"2015","journal-title":"J Med Assoc Thai."},{"key":"B24","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1007\/s00134-010-2002-6","article-title":"Probiotics versus antibiotic decontamination of the digestive tract: infection and mortality","volume":"37","author":"Oudhuis","year":"2011","journal-title":"Intensive Care Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"R290","DOI":"10.1186\/cc10579","article-title":"Effects of probiotics on serum levels of Th1\/Th2 cytokine and clinical outcomes in severe traumatic brain-injured patients: a prospective randomized pilot study","volume":"15","author":"Tan","year":"2011","journal-title":"Crit Care."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1007\/s00134-010-1927-0","article-title":"Probiotics in the critically ill patient: a double blind, randomized, placebo-controlled trial","volume":"36","author":"Barraud","year":"2010","journal-title":"Intensive Care Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1164\/rccm.200912-1853OC","article-title":"Probiotic prophylaxis of ventilator-associated pneumonia: a blinded, randomized, controlled trial","volume":"182","author":"Morrow","year":"2010","journal-title":"Am J Respir Crit Care Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1007\/s00134-008-1368-1","article-title":"Effect of synbiotic therapy on the incidence of ventilator associated pneumonia in critically ill patients: a randomised, double-blind, placebo-controlled trial","volume":"35","author":"Knight","year":"2009","journal-title":"Intensive Care Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1097\/TA.0b013e31819d979e","article-title":"Pro- and synbiotics to control inflammation and infection in patients with multiple injuries","volume":"67","author":"Giamarellos-Bourboulis","year":"2009","journal-title":"J Trauma."},{"key":"B30","doi-asserted-by":"publisher","first-page":"R69","DOI":"10.1186\/cc6907","article-title":"Oral probiotic and prevention of Pseudomonas aeruginosa infections: a randomized, double-blind, placebo-controlled pilot study in intensive care unit patients","volume":"12","author":"Forestier","year":"2008","journal-title":"Crit Care."},{"key":"B31","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1177\/0148607107031002119","article-title":"Synbiotics, prebiotics, glutamine, or peptide in early enteral nutrition: a randomized study in trauma patients","volume":"31","author":"Spindler-Vesel","year":"2007","journal-title":"JPEN J Parenter Enteral Nutr."},{"key":"B32","doi-asserted-by":"publisher","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration's tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ."},{"key":"B33","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analyses","volume":"327","author":"Higgins","year":"2003","journal-title":"BMJ."},{"key":"B34","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1136\/bmj.310.6977.452","article-title":"The number needed to treat: a clinically useful measure of treatment effect","volume":"310","author":"Cook","year":"1995","journal-title":"BMJ."},{"key":"B35","doi-asserted-by":"publisher","first-page":"2782","DOI":"10.1099\/ijsem.0.004107","article-title":"A taxonomic note on the genus Lactobacillus: Description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae","volume":"70","author":"Zheng","year":"2020","journal-title":"Int J Syst Evol Microbiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"R136","DOI":"10.1186\/cc7109","article-title":"Use of the probiotic Lactobacillus plantarum 299 to reduce pathogenic bacteria in the oropharynx of intubated patients: a randomised controlled open pilot study","volume":"12","author":"Klarin","year":"2008","journal-title":"Crit Care."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.1007\/s00268-005-0653-1","article-title":"Benefits of a synbiotic formula (Synbiotic 2000Forte) in critically Ill trauma patients: early results of a randomized controlled trial","volume":"30","author":"Kotzampassi","year":"2006","journal-title":"World J Surg."},{"key":"B38","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1378\/chest.12-0679","article-title":"Lack of efficacy of probiotics in preventing ventilator-associated pneumonia probiotics for ventilator-associated pneumonia: a systematic review and meta-analysis of randomized controlled trials","volume":"142","author":"Gu","year":"2012","journal-title":"Chest."},{"key":"B39","doi-asserted-by":"publisher","first-page":"e83934","DOI":"10.1371\/journal.pone.0083934","article-title":"Probiotics for preventing ventilator-associated pneumonia: a systematic review and meta-analysis of high-quality randomized controlled trials","volume":"8","author":"Wang","year":"2013","journal-title":"PLoS ONE."},{"key":"B40","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1186\/s13054-016-1434-y","article-title":"Probiotic and synbiotic therapy in critical illness: a systematic review and meta-analysis","volume":"19","author":"Manzanares","year":"2016","journal-title":"Crit Care."},{"key":"B41","doi-asserted-by":"publisher","first-page":"717","DOI":"10.3389\/fphar.2017.00717","article-title":"Probiotics for preventing ventilator-associated pneumonia in mechanically ventilated patients: a meta-analysis with trial sequential analysis","volume":"8","author":"Weng","year":"2017","journal-title":"Front Pharmacol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1016\/j.cgh.2015.05.027","article-title":"Patients receiving prebiotics and probiotics before liver transplantation develop fewer infections than controls: a systematic review and meta-analysis","volume":"13","author":"Sawas","year":"2015","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.ccc.2015.11.004","article-title":"The gut as the motor of multiple organ dysfunction in critical illness","volume":"32","author":"Klingensmith","year":"2016","journal-title":"Crit Care Clin."},{"key":"B44","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.molmed.2013.08.004","article-title":"Redefining the gut as the motor of critical illness","volume":"20","author":"Mittal","year":"2014","journal-title":"Trends Mol Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1017\/ice.2018.30","article-title":"Ventilator bundle compliance and risk of ventilator-associated events","volume":"39","author":"Harris","year":"2018","journal-title":"Infect Control Hosp Epidemiol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.1001\/jama.2012.3507","article-title":"Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis","volume":"307","author":"Hempel","year":"2012","journal-title":"JAMA."},{"key":"B47","doi-asserted-by":"publisher","first-page":"CD004827","DOI":"10.1002\/14651858.CD004827.pub4","article-title":"Probiotics for the prevention of pediatric antibiotic-associated diarrhea","volume":"12","author":"Goldenberg","year":"2015","journal-title":"Cochrane Database Syst Rev."},{"key":"B48","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.copbio.2020.01.005","article-title":"Molecular mechanisms of probiotic prevention of antibiotic-associated diarrhea","volume":"61","author":"Mekonnen","year":"2020","journal-title":"Curr Opin Biotechnol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"R2","DOI":"10.1186\/cc11919","article-title":"Small studies may overestimate the effect sizes in critical care meta-analyses: a meta-epidemiological study","volume":"17","author":"Zhang","year":"2013","journal-title":"Crit Care."},{"key":"B50","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2021.798827\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T15:17:10Z","timestamp":1643296630000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2021.798827\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,27]]},"references-count":50,"alternative-id":["10.3389\/fnut.2021.798827"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2021.798827","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,27]]},"article-number":"798827"}}