{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T21:55:15Z","timestamp":1779918915746,"version":"3.53.1"},"reference-count":120,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T00:00:00Z","timestamp":1657238400000},"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>Ventilator-associated pneumonia (VAP) is one of the common critical complications of nosocomial infection (NI) in invasive mechanically ventilated intensive care unit (ICU) patients. The efficacy of total parenteral nutrition (TPN), enteral nutrition and\/or adjuvant peripheral parenteral nutrition (EPN) supplemented with or without probiotic, prebiotic, and synbiotic therapies in preventing VAP among these patients has been questioned. We aimed to systematically and comprehensively summarize all available studies to generate the best evidence of VAP prevention for invasive mechanically ventilated ICU patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Randomized controlled trials (RCTs) for the administration of TPN, EPN, probiotics-supplemented EPN, prebiotics-supplemented EPN, and synbiotics-supplemented EPN for VAP prevention in invasive mechanically ventilated ICU patients were systematically retrieved from four electronic databases. The incidence of VAP was the primary outcome and was determined by the random-effects model of a Bayesian framework. The secondary outcomes were NI, ICU and hospital mortality, ICU and hospital length of stay, and mechanical ventilation duration. The registration number of Prospero is CRD42020195773.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 8339 patients from 31 RCTs were finally included in network meta-analysis. The primary outcome showed that probiotic-supplemented EPN had a higher correlation with the alleviation of VAP than EPN in critically invasive mechanically ventilated patients (odds ratio [OR] 0.75; 95% credible intervals [CrI] 0.58\u20130.95). Subgroup analyses showed that probiotic-supplemented EPN prevented VAP in trauma patients (OR 0.30; 95% CrI 0.13\u20130.83), mixed probiotic strain therapy was more effective in preventing VAP than EPN therapy (OR 0.55; 95% CrI 0.31\u20130.97), and low-dose probiotic therapy (less than 10<jats:sup>10<\/jats:sup> CFU per day) was more associated with lowered incidence of VAP than EPN therapy (OR 0.16; 95% CrI 0.04\u20130.64). Secondary outcomes indicated that synbiotic-supplemented EPN therapy was more significantly related to decreased incidence of NI than EPN therapy (OR 0.34; 95% CrI 0.11\u20130.85). Prebiotic-supplemented EPN administration was the most effective in preventing diarrhea (OR 0.05; 95% CrI 0.00\u20130.71).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Probiotic supplementation shows promise in reducing the incidence of VAP in critically invasive mechanically ventilated patients. Currently, low quality of evidence reduces strong clinical recommendations. Further high-quality RCTs are needed to conclusively prove these findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Systamatic Review Registration<\/jats:title><jats:p>[<jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/display_record.php?ID=CRD42020195773<\/jats:ext-link>], identifier [CRD42020195773].<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2022.919156","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T09:56:25Z","timestamp":1657274185000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Probiotic Supplementation Prevents the Development of Ventilator-Associated Pneumonia for Mechanically Ventilated ICU Patients: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials"],"prefix":"10.3389","volume":"9","author":[{"given":"Cong","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangjie","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,8]]},"reference":[{"key":"B1","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":"B2","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1007\/s00134-020-06036-z","article-title":"Diagnosis of ventilator-associated pneumonia in critically ill adult patients-a systematic review and meta-analysis.","volume":"46","author":"Fernando","year":"2020","journal-title":"Intensive Care Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1097\/TA.0b013e3181f9fb51","article-title":"Ventilator-associated pneumonia is more common and of less consequence in trauma patients compared with other critically ill patients.","volume":"69","author":"Cook","year":"2010","journal-title":"J Trauma."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1007\/s10096-016-2703-z","article-title":"Nosocomial pneumonia in 27 ICUs in Europe: perspectives from the EU-VAP\/CAP study.","volume":"36","author":"Koulenti","year":"2017","journal-title":"Eur J Clin Microbiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1097\/MCC.0000000000000123","article-title":"Chronic obstructive pulmonary disease and the risk for ventilator-associated pneumonia.","volume":"20","author":"Rouze","year":"2014","journal-title":"Curr Opin Crit Care."},{"key":"B6","doi-asserted-by":"publisher","first-page":"R65","DOI":"10.1186\/cc11312","article-title":"Ventilator-associated pneumonia and ICU mortality in severe ARDS patients ventilated according to a lung-protective strategy.","volume":"16","author":"Forel","year":"2012","journal-title":"Crit Care."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1726","DOI":"10.1097\/CCM.0000000000002652","article-title":"Nosocomial infections during extracorporeal membrane oxygenation: incidence, etiology, and impact on patients\u2019 outcome.","volume":"45","author":"Grasselli","year":"2017","journal-title":"Crit Care Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2039","DOI":"10.1001\/jamainternmed.2013.9763","article-title":"Health care-associated infections: a meta-analysis of costs and financial impact on the US health care system.","volume":"173","author":"Zimlichman","year":"2013","journal-title":"JAMA Intern Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1378\/chest.08-1116","article-title":"Predictors of 30-day mortality and hospital costs in patients with ventilator-associated pneumonia attributed to potentially antibiotic-resistant gram-negative bacteria.","volume":"134","author":"Kollef","year":"2008","journal-title":"Chest."},{"key":"B10","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":"B11","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1164\/rccm.201105-0867OC","article-title":"Attributable mortality of ventilator-associated pneumonia: a reappraisal using causal analysis.","volume":"184","author":"Bekaert","year":"2011","journal-title":"Am J Respirat Cri Care Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e20210198","DOI":"10.36416\/1806-3756\/e20210198","article-title":"New insights into pneumonia in patients on prolonged mechanical ventilation: need for a new paradigm addressing dysbiosis.","volume":"47","author":"Rello","year":"2021","journal-title":"J Brasil Pneumol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s13613-021-00976-5","article-title":"The role of the microbiota in the management of intensive care patients.","volume":"12","author":"Szychowiak","year":"2022","journal-title":"Ann Intensive Care."},{"key":"B14","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":"B15","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1097\/MCC.0000000000000321","article-title":"Role of the microbiome, probiotics, and \u2018dysbiosis therapy\u2019 in critical illness.","volume":"22","author":"Wischmeyer","year":"2016","journal-title":"Curr Opin Crit Care."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1099\/jmm.0.000579","article-title":"The function of probiotics on the treatment of ventilator-associated pneumonia (VAP): facts and gaps.","volume":"66","author":"Karacaer","year":"2017","journal-title":"J Med Microbiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1080\/10408398.2020.1843396","article-title":"Antibiotic-induced gut dysbiosis and barrier disruption and the potential protective strategies.","volume":"62","author":"Duan","year":"2020","journal-title":"Crit Rev Food Sci Nutr."},{"key":"B18","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1378\/chest.06-2156","article-title":"Probiotics for preventing and treating nosocomial infections: review of current evidence and recommendations.","volume":"132","author":"Isakow","year":"2007","journal-title":"Chest."},{"key":"B19","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/j.chest.2016.10.006","article-title":"Blurred lines: dysbiosis and probiotics in the ICU.","volume":"151","author":"Morrow","year":"2017","journal-title":"Chest."},{"key":"B20","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":"B21","doi-asserted-by":"publisher","first-page":"521","DOI":"10.3920\/BM2016.0222","article-title":"How do probiotics and prebiotics function at distant sites.","volume":"8","author":"Reid","year":"2017","journal-title":"Benef Microb."},{"key":"B22","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1038\/s41591-019-0439-x","article-title":"The pros, cons, and many unknowns of probiotics.","volume":"25","author":"Suez","year":"2019","journal-title":"Nat Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/nrgastro.2017.75","article-title":"Expert consensus document: the international scientific association for probiotics and prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics.","volume":"14","author":"Gibson","year":"2017","journal-title":"Nat Rev Gastroenterol Hepatol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1017\/S0007114510003363","article-title":"Prebiotic effects: metabolic and health benefits.","volume":"104","author":"Roberfroid","year":"2010","journal-title":"Br J Nutr."},{"key":"B25","doi-asserted-by":"publisher","first-page":"61","DOI":"10.3920\/BM2013.0050","article-title":"Yoghurt and probiotic bacteria in dietary guidelines of the member states of the European Union.","volume":"5","author":"Smug","year":"2014","journal-title":"Benef Microb."},{"key":"B26","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1177\/0148607115621863","article-title":"Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: society of critical care medicine (SCCM) and American society for parenteral and enteral nutrition (A.S.P.E.N.).","volume":"40","author":"McClave","year":"2016","journal-title":"JPEN J Parenter Enteral Nutr."},{"key":"B27","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1080\/11024150201680019","article-title":"Importance of the early increase in intestinal permeability in critically ill patients.","volume":"168","author":"Ammori","year":"2002","journal-title":"Eur J Surg."},{"key":"B28","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1177\/0148607107031003246","article-title":"Is there evidence that the gut contributes to mucosal immunity in humans?","volume":"31","author":"Kang","year":"2007","journal-title":"JPEN J Parenter Enteral Nutr."},{"key":"B29","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1093\/ajcn\/74.4.534","article-title":"Enteral compared with parenteral nutrition: a meta-analysis.","volume":"74","author":"Braunschweig","year":"2001","journal-title":"Am J Clin Nutr."},{"key":"B30","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1177\/0148607103027005355","article-title":"Canadian critical care clinical practice guidelines committee. Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients.","volume":"27","author":"Heyland","year":"2003","journal-title":"JPEN J Parenter Enteral Nutr."},{"key":"B31","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1016\/j.nut.2004.06.003","article-title":"Does enteral nutrition compared to parenteral nutrition result in better outcomes in critically ill adult patients? A systematic review of the literature.","volume":"20","author":"Gramlich","year":"2004","journal-title":"Nutrition."},{"key":"B32","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1097\/01.CCM.0000150960.36228.C0","article-title":"A meta-analysis of treatment outcomes of early enteral versus early parenteral nutrition in hospitalized patients.","volume":"33","author":"Peter","year":"2005","journal-title":"Crit Care Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1007\/s00134-004-2511-2","article-title":"Parenteral vs. enteral nutrition in the critically ill patient: a meta-analysis of trials using the intention to treat principle.","volume":"31","author":"Simpson","year":"2005","journal-title":"Intensive Care Med."},{"key":"B34","first-page":"262","article-title":"Effects of probiotics on prevalence of ventilator-associated pneumonia in multitrauma patients: a randomized clinical trial.","volume":"25","author":"Nazari","year":"2020","journal-title":"Trauma Month."},{"key":"B35","doi-asserted-by":"publisher","first-page":"2287","DOI":"10.15419\/bmrat.v5i5.442","article-title":"Prebiotic prophylaxis of ventilator-associated pneumonia: a randomized clinical trial.","volume":"5","author":"Kooshki","year":"2018","journal-title":"Biomed Res Ther."},{"key":"B36","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":"B37","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":"B38","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1378\/chest.12-1745","article-title":"Impact of the administration of probiotics on mortality in critically ill adult patients: a meta-analysis of randomized controlled trials.","volume":"143","author":"Barraud","year":"2013","journal-title":"Chest."},{"key":"B39","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1097\/CCM.0b013e3181c8fe4b","article-title":"Impact of the administration of probiotics on the incidence of ventilator-associated-pneumonia: a meta-analysis of randomized controlled trials.","volume":"38","author":"Siempos","year":"2010","journal-title":"Crit Care Med."},{"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":"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":"B42","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":"B43","doi-asserted-by":"crossref","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":"B44","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":"B45","doi-asserted-by":"publisher","first-page":"287","DOI":"10.5505\/tjtes.2017.34514","article-title":"Effect of \u03b2-glucan on serum levels of IL-12, hs-CRP, and clinical outcomes in multiple-trauma patients: a prospective randomized study.","volume":"24","author":"Fazilaty","year":"2018","journal-title":"Ulus Travma Acil Cerrahi Derg."},{"key":"B46","doi-asserted-by":"publisher","first-page":"83","DOI":"10.22159\/ajpcr.2020.v13i10.38114","article-title":"Early probiotics in preventing ventilator-Associated pneumonia after multiple trauma.","volume":"13","author":"Habib","year":"2020","journal-title":"Asian J Pharm Clin Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1177\/0148607101025006299","article-title":"Early enteral nutrition in critically ill patients with a high-protein diet enriched with arginine, fiber, and antioxidants compared with a standard high-protein diet. The effect on nosocomial infections and outcome.","volume":"25","author":"Caparros","year":"2001","journal-title":"J Parenter Enteral Nutr."},{"key":"B48","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":"B49","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":"B50","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":"B51","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 Thailand."},{"key":"B52","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":"B53","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":"2018","journal-title":"Nutr Clin Pract."},{"key":"B54","doi-asserted-by":"publisher","first-page":"21","DOI":"10.7860\/JCDR\/2019\/42325.13084","article-title":"A randomised controlled trial of lactobacillus in the prevention of ventilator associated pneumonia.","volume":"13","author":"Anandaraj","year":"2019","journal-title":"J Clin Diagnostic Res."},{"key":"B55","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0140-6736(17)32146-3","article-title":"Enteral versus parenteral early nutrition in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2).","volume":"391","author":"Reignier","year":"2018","journal-title":"Lancet."},{"key":"B56","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1080\/15563650902936664","article-title":"Early hypocaloric enteral nutritional supplementation in acute organophosphate poisoning \u2013 a prospective randomized trial.","volume":"47","author":"Moses","year":"2009","journal-title":"Clin Toxicol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"414","DOI":"10.5152\/balkanmedj.2012.043","article-title":"Glutamine supplemented parenteral nutrition to prevent ventilator-associated pneumonia in the intensive care unit.","volume":"29","author":"Aydo\u011fmu\u015f","year":"2012","journal-title":"Balkan Med J."},{"key":"B58","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1177\/0884533611405790","article-title":"Effect of enteral versus parenteral nutrition on outcome of medical patients requiring mechanical ventilation.","volume":"26","author":"Altintas","year":"2011","journal-title":"Nutr Clin Pract."},{"key":"B59","doi-asserted-by":"publisher","first-page":"693188","DOI":"10.3389\/fmed.2021.693188","article-title":"Synbiotic therapy prevents nosocomial infection in critically ill adult patients: a systematic review and network meta-analysis of randomized controlled trials based on a bayesian framework.","volume":"8","author":"Li","year":"2021","journal-title":"Front Med (Lausanne)."},{"key":"B60","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1517\/14740338.2014.872627","article-title":"A systematic review of the safety of probiotics.","volume":"13","author":"Didari","year":"2014","journal-title":"Expert Opin Drug Saf."},{"key":"B61","doi-asserted-by":"publisher","first-page":"000250","DOI":"10.1099\/acmi.0.000250","article-title":"Bloodstream infection by Saccharomyces cerevisiae in a COVID-19 patient receiving probiotic supplementation in the ICU in Brazil.","volume":"3","author":"Pinto","year":"2021","journal-title":"Access Microbiol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3920\/BM2014.0079","article-title":"The administration of probiotics and synbiotics in immune compromised adults: is it safe?","volume":"6","author":"Van den Nieuwboer","year":"2015","journal-title":"Benef Microb."},{"key":"B63","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/S0140-6736(08)60207-X","article-title":"Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial.","volume":"371","author":"Besselink","year":"2008","journal-title":"Lancet."},{"key":"B64","doi-asserted-by":"publisher","first-page":"3105","DOI":"10.1002\/sim.1875","article-title":"Combination of direct and indirect evidence in mixed treatment comparisons.","volume":"23","author":"Lu","year":"2004","journal-title":"Stat Med."},{"key":"B65","author":"Li","year":"2020","journal-title":"Effectiveness of Probiotic, Prebiotic, and Synbiotic Therapies in Improving Ventilator-Associated Pneumonia in Critically ill Adult:A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials Based on a Bayesian Framework."},{"key":"B66","first-page":"p. 2012","author":"Higgins","year":"2012","journal-title":"Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0."},{"key":"B67","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1038\/s41575-020-0344-2","article-title":"The International Scientific Association for Probiotics and prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics.","volume":"17","author":"Swanson","year":"2020","journal-title":"Nat Rev Gastroenterol Hepatol."},{"key":"B68","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":"B69","article-title":"Chapter 8: assessing risk of bias in included studies.","author":"Higgins","year":"2011","journal-title":"Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0."},{"key":"B70","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1177\/096228029600500402","article-title":"Markov chain monte carlo methods in biostatistics.","volume":"5","author":"Gelman","year":"1996","journal-title":"Stat Methods Med Res."},{"key":"B71","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.jclinepi.2010.03.016","article-title":"Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial.","volume":"64","author":"Salanti","year":"2011","journal-title":"J Clin Epidemiol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.jclinepi.2014.08.012","article-title":"Predictive distributions were developed for the extent of heterogeneity in meta-analyses of continuous outcome data.","volume":"68","author":"Rhodes","year":"2015","journal-title":"J Clin Epidemiol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1002\/sim.6381","article-title":"Predictive distributions for between-study heterogeneity and simple methods for their application in Bayesian meta-analysis.","volume":"34","author":"Turner","year":"2015","journal-title":"Stat Med."},{"key":"B74","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1002\/sim.3767","article-title":"Checking consistency in mixed treatment comparison meta-analysis.","volume":"29","author":"Dias","year":"2010","journal-title":"Stat Med."},{"key":"B75","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1002\/jrsm.1044","article-title":"Consistency and inconsistency in network meta-analysis: concepts and models for multi-arm studies.","volume":"3","author":"Higgins","year":"2012","journal-title":"Res Synth Methods."},{"key":"B76","first-page":"123","article-title":"Effects of the continuous intake of Lactobacillus casei strain Shirota-fermented milk on risk management of long-term inpatients at health service facilities for the elderly.","volume":"6","author":"Bian","year":"2011","journal-title":"Int J Probiot Prebiot."},{"key":"B77","year":"2009","journal-title":"Accepted Claims About the Nature of Probiotic Microorganisms in Food."},{"key":"B78","year":"2013","journal-title":"Commissione Unica per la Nutrizione e la Dietetica. Guidelines on Probiotics and Prebiotics."},{"key":"B79","doi-asserted-by":"publisher","first-page":"postgradmedj-2021-140376","DOI":"10.1136\/postgradmedj-2021-140376","article-title":"Cohort study of the APACHE II score and mortality for different types of intensive care unit patients.","volume":"8","author":"Sungono","year":"2021","journal-title":"Postgrad Med J."},{"key":"B80","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.ijid.2014.11.005","article-title":"A comparison of APACHE II and CPIS scores for the prediction of 30-day mortality in patients with ventilator-associated pneumonia.","volume":"30","author":"Zhou","year":"2015","journal-title":"Int J Infect Dis."},{"key":"B81","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1186\/s12873-021-00547-8","article-title":"Prognostic scores and early management of septic patients in the emergency department of a secondary hospital: results of a retrospective study.","volume":"21","author":"Colussi","year":"2021","journal-title":"BMC Emerg Med."},{"key":"B82","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1002\/jpen.2267","article-title":"Guidelines for the provision of nutrition support therapy in the adult critically Ill patient: American society for parenteral and enteral nutrition.","volume":"46","author":"Compher","year":"2022","journal-title":"JPEN J Parenter Enteral Nutr."},{"key":"B83","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.clnu.2018.08.037","article-title":"ESPEN guideline on clinical nutrition in the intensive care unit.","volume":"38","author":"Singer","year":"2019","journal-title":"Clin Nutr."},{"key":"B84","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/j.jclinepi.2007.06.006","article-title":"Adjusted indirect comparison may be less biased than direct comparison for evaluating new pharmaceutical interventions.","volume":"61","author":"Song","year":"2008","journal-title":"J Clin Epidemiol."},{"key":"B85","doi-asserted-by":"publisher","first-page":"e76654","DOI":"10.1371\/journal.pone.0076654","article-title":"Graphical tools for network meta-analysis in STATA.","volume":"8","author":"Chaimani","year":"2013","journal-title":"PLoS One."},{"key":"B86","doi-asserted-by":"publisher","first-page":"e99682","DOI":"10.1371\/journal.pone.0099682","article-title":"Evaluating the quality of evidence from a network meta-analysis.","volume":"9","author":"Salanti","year":"2014","journal-title":"PLoS One."},{"key":"B87","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":"B88","doi-asserted-by":"publisher","first-page":"177S","DOI":"10.1378\/chest.117.4_suppl_2.177S","article-title":"Evidence-based assessment of diagnostic tests for ventilator-associated pneumonia. Executive summary.","volume":"117","author":"Grossman","year":"2000","journal-title":"Chest."},{"key":"B89","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1164\/rccm.200405-644ST","article-title":"America IDSo: Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.","volume":"171","author":"Society","year":"2005","journal-title":"Am J Respir Crit Care Med."},{"key":"B90","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1164\/ajrccm\/143.5_Pt_1.1121","article-title":"Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic \u201cBlind\u201d bronchoalveolar lavage fluid.","volume":"143","author":"Pugin","year":"1991","journal-title":"Am Rev Respir Dis."},{"key":"B91","first-page":"803","article-title":"Probiotic effects in prevention from ventilator-associated pneumonia.","volume":"17","author":"Zarinfar","year":"2016","journal-title":"Koomesh."},{"key":"B92","doi-asserted-by":"publisher","first-page":"106471","DOI":"10.1016\/j.ijantimicag.2021.106471","article-title":"A four-probiotic preparation for ventilator-associated pneumonia in multi-trauma patients: results of a randomized clinical trial.","volume":"59","author":"Tsilika","year":"2022","journal-title":"Int J Antimicrob Agent.s"},{"key":"B93","doi-asserted-by":"publisher","first-page":"2240","DOI":"10.1128\/IAI.72.4.2240-2247.2004","article-title":"Probiotic bifidobacteria protect mice from lethal infection with Shiga toxin-producing Escherichia coli O157:H7.","volume":"72","author":"Asahara","year":"2004","journal-title":"Infect Immun."},{"key":"B94","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.nut.2018.07.017","article-title":"Probiotic and synbiotic therapy in the critically ill: State of the art.","volume":"59","author":"Davison","year":"2019","journal-title":"Nutrition."},{"key":"B95","doi-asserted-by":"publisher","first-page":"3290","DOI":"10.1097\/CCM.0b013e318260cc33","article-title":"Probiotics in the critically ill: a systematic review of the randomized trial evidence.","volume":"40","author":"Petrof","year":"2012","journal-title":"Crit Care Med."},{"key":"B96","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":"B97","first-page":"174","article-title":"The effect of early enteral nutrition supplemented with probiotics on ventilator-associated pneumonia in patients with severe stroke.","volume":"31","author":"Jin","year":"2019","journal-title":"Chin J Microecol."},{"key":"B98","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1093\/jac\/dkn086","article-title":"Profound effect of study design factors on ventilator-associated pneumonia incidence of prevention studies: benchmarking the literature experience.","volume":"61","author":"Hurley","year":"2008","journal-title":"J Antimicrob Chemother."},{"key":"B99","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.copbio.2017.09.007","article-title":"Shared mechanisms among probiotic taxa: implications for general probiotic claims.","volume":"49","author":"Sanders","year":"2018","journal-title":"Curr Opin Biotechnol."},{"key":"B100","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1097\/SHK.0000000000001654","article-title":"Gut microbiota dysbiosis as a target for improved post-surgical outcomes and improved patient care: a review of current literature.","volume":"55","author":"Fatema","year":"2021","journal-title":"Shock."},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1097\/ANA.0000000000000789","article-title":"Characteristics of gut microbiome after traumatic brain injury.","author":"Mahajan","year":"2021","journal-title":"J Neurosurg Anesthesiol."},{"key":"B102","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1186\/s40168-018-0494-4","article-title":"Probiotic Bifidobacterium strains and galactooligosaccharides improve intestinal barrier function in obese adults but show no synergism when used together as synbiotics.","volume":"6","author":"Krumbeck","year":"2018","journal-title":"Microbiome."},{"key":"B103","doi-asserted-by":"publisher","first-page":"821","DOI":"10.3390\/microorganisms8060821","article-title":"Pathogenesis-targeted preventive strategies for multidrug resistant ventilator-associated pneumonia: a narrative review.","volume":"8","author":"Cotoia","year":"2020","journal-title":"Microorganisms."},{"key":"B104","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1186\/cc8204","article-title":"Clinical review\u2013 scoring systems in the critically ill.","volume":"14","author":"Vincent","year":"2010","journal-title":"Crit Care."},{"key":"B105","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.12669\/pjms.325.10080","article-title":"Better prognostic marker in ICU \u2013 APACHE II, SOFA or SAP II!","volume":"32","author":"Naqvi","year":"2016","journal-title":"Pak J Med Sci."},{"key":"B106","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1378\/chest.11-0330","article-title":"Severity scoring in the critically ill: part 1\u2013interpretation and accuracy of outcome prediction scoring systems.","volume":"141","author":"Breslow","year":"2012","journal-title":"Chest."},{"key":"B107","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1097\/MCC.0000000000000138","article-title":"A history of outcome prediction in the ICU.","volume":"20","author":"Zimmerman","year":"2014","journal-title":"Curr Opin Crit Care."},{"key":"B108","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1177\/0148607107031002119","article-title":"Synbiotics prebiotics glutamine or peptide in early enteral nutrition.","volume":"31","author":"Spindler-Vesel","year":"2006","journal-title":"J Parenter Enteral Nutr."},{"key":"B109","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":"B110","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1093\/ajcn\/55.3.753","article-title":"Defining and reporting diarrhea in tube-fed patients-what a mess!","volume":"55","author":"Bliss","year":"1992","journal-title":"Am J Clin Nutr."},{"key":"B111","doi-asserted-by":"publisher","first-page":"296","DOI":"10.5005\/jp-journals-10071-23753","article-title":"Concordance between the national healthcare safety network (NHSN) surveillance criteria and clinical pulmonary infection score (CPIS) criteria for diagnosis of ventilator-associated pneumonia (VAP).","volume":"25","author":"Gunalan","year":"2021","journal-title":"Indian J Crit Care Med."},{"key":"B112","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1177\/0148607116651758","article-title":"Diarrhea in critically ill patients: the role of enteral feeding.","volume":"40","author":"de Brito-Ashurst","year":"2016","journal-title":"JPEN J Parenter Enteral Nutr."},{"key":"B113","first-page":"CD009066","article-title":"Probiotics for preventing ventilator-associated pneumonia.","volume":"10","author":"Bo","year":"2014","journal-title":"Cochrane Database Syst Rev."},{"key":"B114","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.nut.2017.06.024","article-title":"Probiotics and gastrointestinal conditions: an overview of evidence from the Cochrane Collaboration.","volume":"45","author":"Parker","year":"2018","journal-title":"Nutrition."},{"key":"B115","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1038\/s41575-021-00440-6","article-title":"The international scientific association of probiotics and prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics.","volume":"18","author":"Salminen","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol."},{"key":"B116","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1007\/s00134-006-0238-y","article-title":"Early enteral immunonutrition vs. Parenteral nutrition in critically ill patients without severe sepsis: a randomized clinical trial.","volume":"32","author":"Radrizzani","year":"2006","journal-title":"Intensive Care Med."},{"key":"B117","first-page":"15","article-title":"Enteral versus parenteral nutrition in mechanically ventilated patients.","volume":"56","author":"Abdulmeguid","year":"2007","journal-title":"Neurol Croatica."},{"key":"B118","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.4037\/ajcc2010976","article-title":"Decrease in frequency of liquid stool in enterally fed critically ill patients given the multispecies probiotic VSL#3: a pilot trial.","volume":"19","author":"Frohmader","year":"2010","journal-title":"Am J Crit Care."},{"key":"B119","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.jcrc.2015.12.008","article-title":"Microbial cell preparation in enteral feeding in critically ill patients: a randomized, double-blind, placebo-controlled clinical trial.","volume":"32","author":"Malik","year":"2016","journal-title":"J Crit Care."},{"key":"B120","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1186\/s13054-019-2403-z","article-title":"Impact of nutrition route on microaspiration in critically ill patients with shock: a planned ancillary study of the NUTRIREA-2 trial.","volume":"23","author":"Nseir","year":"2019","journal-title":"Crit Care."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.919156\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T09:56:45Z","timestamp":1657274205000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.919156\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,8]]},"references-count":120,"alternative-id":["10.3389\/fnut.2022.919156"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2022.919156","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,8]]},"article-number":"919156"}}