HealthResJ, health, medicine, nursing, research https://ejournals.epublishing.ekt.gr/index.php/HealthResJ/sitemap

The effects of probiotics, prebiotics and synbiotics on infections and clinical outcomes in critical illness: A systematic review


Published: Apr 10, 2025
Keywords:
Probiotics synbiotic critically ill patients enteral nutrition
Orsalia Konsta
Vasiliki Linardatou
Yiannis Papachatzakis
Eleftherios Karatzanos
Anastasios Philippou
Ioannis Vasileiadis
Yiannis Manios
Serafim Nanas
Abstract

Background: Critically ill patients treated in intensive care units (ICU) are characterized by a qualitative and quantitative change in the composition of their intestinal microflora, leading to a reduction in commensal flora and an overgrowth of potentially pathogenic bacteria, which increase susceptibility to nosocomial infections and compromise their outcome. Probiotics are live, non-pathogenic microorganisms that can provide health benefits to the host, such as restoring the balance of the microbiota and positive effects on immune function and gastrointestinal tract structure and function, when ingested in sufficient quantities. This systematic review aimed to evaluate the effects of probiotics/prebiotics and synbiotic mixtures on infections and clinical outcomes in critically ill patients.


Method and Material: Randomized clinical trials (RCTs) were reviewed in PubMed, EMBASE, CINAHL, CENTRAL and COHRANE from January 2004 to November 2024. Initially, 81 RCTs were selected, which evaluated the effects of probiotics or synbiotics versus placebo or prebiotics on clinical outcomes in adult ICU patients. Following the implementation of the PRISMA statement, 25 studies were finally included in this systematic review, and 5.106 patients were identified for analysis. The total number of new infections was the primary outcome. Secondary outcomes included mortality, ICU-acquired pneumonia, duration of mechanical ventilation (MV), length of stay (LOS) in the ICU, hospital and diarrhea.


Results: Probiotics were associated with a significant reduction in infections and ventilator-associated pneumonia (VAP), shorter duration of MV, ICU and hospital LOS and fewer episodes and shorter duration of diarrhea. No effect on ICU or hospital mortality was observed. Moreover, the greatest improvement in most outcomes was seen with probiotics alone compared to synbiotics mixtures, with a higher dose of probiotics (≥5 × 109 CFU/day) and with at least 14-15 days of supplementation.


Conclusion: Probiotics appear to reduce infectious complications, including ventilator-associated pneumonia, in critically ill patients and positively influence ICU and hospital LOS, days on MV and diarrhea. However, clinical heterogeneity and potential publication bias limit a clear clinical recommendation. Further research on probiotics in critically ill patients and more high-quality clinical trials are needed to demonstrate these benefits.

Article Details
  • Section
  • Systemic Review
Downloads
Download data is not yet available.
References
Alverdy JC, Chang EB. The re-emerging role of the intesti-nal microflora in critical illness and inflammation: why the gut hypothesis of sepsis syndrome will not go away. J Leu-koc Biol. 2008;83(3):461–6.
Rosen R, Amirault J, Liu H, Mitchell P, Hu L, Khatwa U, et al. Changes in gastric and lung microflora with acid sup-pression: Acid suppression and bacterial growth. JAMA Pediatr. 2014;168(10):932–7.
Mittal R, Coopersmith CM. Redefining the gut as the motor of critical illness. Trends Mol Med. 2014;20(4):214–23.
Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, Reddy DN. Role of the normal gut microbiota. World J Gastroenterol. 2015;21(29).
Barraud D, Bollaert PE, Gibot S. Impact of the administra-tion of probiotics on mortality in critically ill adult patients: A meta-analysis of randomized controlled trials. Chest. 2013;143(3):646–55.
Wang G, Wen J, Xu L, Zhou S, Gong M, Wen P, et al. Effect of enteral nutrition and ecoimmunonutrition on bacterial translocation and cytokine production in patients with se-vere acute pancreatitis. Journal of Surgical Research. 2013;183(2):592–7.
Zeng J, Wang CT, Zhang FS, Qi F, Wang SF, Ma S, et al. Effect of probiotics on the incidence of ventilator-associated pneumonia in critically ill patients: a random-ized controlled multicenter trial. Intensive Care Med. 2016 Jun 1;42(6):1018–28.
McNaught CE, Woodcock NP, Anderson ADG, MacFie J. A prospective randomised trial of probiotics in critically ill patients. Clinical Nutrition. 2005 Apr;24(2):211–9.
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that eval-uate health care interventions: Explanation and elabora-tion. PLoS Med. 2009;6(7).
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ, et al. Assessing the quality of reports of ran-domized clinical trials: Is blinding necessary? Control Clin Trials. 1996;17(1):1–12.
Jain PK, McNaught CE, Anderson ADG, MacFie J, Mitchell CJ. Influence of synbiotic containing Lactobacillus aci-dophilus La5, Bifidobacterium lactis Bb 12, Streptococcus thermophilus, Lactobacillus bulgaricus and oligofructose on gut barrier function and sepsis in critically ill patients: A randomised controlled tr. Clinical Nutrition. 2004 Aug;23(4):467–75.
Falc˜ao IS, Falc˜ao F, Arruda DE, Jos´ J, De Aguilar-Nascimento JE. Benefits of early enteral nutrition with glu-tamine and probiotics in brain injury patients. Vol. 106, Clinical Science. 2004.
Klarin B, Johansson ML, Molin G, Larsson A, Jeppsson B. Adhesion of the probiotic bacterium Lactobacillus planta-rum 299v onto the gut mucosa in critically ill patients: a randomised open trial. Crit Care. 2005;9(3).
Kotzampassi K, Giamarellos-Bourboulis EJ, Voudouris A, Kazamias P, Eleftheriadis E. Benefits of a synbiotic formula (Synbiotic 2000Forte®) in critically ill trauma patients: Early results of a randomized controlled trial. World J Surg. 2006 Oct;30(10):1848–55.
Spindler-Vesel A, Bengmark S, Vovk I, Cerovic O, Kompan L. or Peptide in Early Enteral Nutrition: A Randomized Study in Trauma Patients. Vol. 31, Journal of Parenteral and Enteral Nutrition. 2007.
Knight DJW, Gardiner D, Banks A, Snape SE, Weston VC, Bengmark S, et al. Effect of synbiotic therapy on the inci-dence of ventilator associated pneumonia in critically ill patients: A randomised, double-blind, placebo-controlled trial. Intensive Care Med. 2009 May;35(5):854–61.
Giamarellos-Bourboulis EJ, Bengmark S, Kanellakopoulou K, Kotzampassi K. Pro- and synbiotics to control inflamma-tion and infection in patients with multiple injuries. Journal of Trauma - Injury, Infection and Critical Care. 2009 Oct;67(4):815–21.
Morrow LE, Kollef MH, Casale TB. Probiotic prophylaxis of ventilator-associated pneumonia: A blinded, randomized, controlled trial. Am J Respir Crit Care Med. 2010 Oct 15;182(8):1058–64.
Frohmader TJ, Chaboyer WP, Robertson IK, Gowardman J. Decrease in frequency of liquid stool in enterally fed criti-cally ill patients given the multispecies probiotic VSL#3: A pilot trial. American Journal of Critical Care. 2010 May;19(3).
Barraud D, Blard C, Hein F, Marçon O, Cravoisy A, Nace L, et al. Probiotics in the critically ill patient: A double blind, randomized, placebo-controlled trial. Intensive Care Med. 2010 Sep;36(9):1540–7.
Tan M, Zhu JC, Du J, Zhang LM, Yin HH. Effects of probiot-ics on serum levels of Th1/Th2 cytokine and clinical out-comes in severe traumatic brain-injured patients: a pro-spective randomized pilot study [Internet]. 2011. Available from: http://ccforum.com/content/15/6/R290
Ferrie S, Daley M. Lactobacillus GG as treatment for Diar-rhea during enteral feeding in critical illness: Randomized controlled trial. Journal of Parenteral and Enteral Nutrition. 2011 Jan;35(1):43–9.
Malik AA, Rajandram R, Tah PC, Hakumat-Rai VR, Chin KF. Microbial cell preparation in enteral feeding in critically ill patients: A randomized, double-blind, placebo-controlled clinical trial. J Crit Care. 2016 Apr 1;32:182–8.
Shimizu K, Yamada T, Ogura H, Mohri T, Kiguchi T, Fujimi S, et al. Synbiotics modulate gut microbiota and reduce enteritis and ventilator-associated pneumonia in patients with sepsis: a randomized controlled trial. Crit Care. 2018 Sep 27;22(1).
Mahmoodpoor A, Hamishehkar H, Asghari R, Abri R, Shadvar K, Sanaie S. 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. Nutrition in Clinical Practice. 2019 Feb 1;34(1):156–62.
Tsaousi. 39th International Symposium on Intensive Care and Emergency Medicine : Brussels, Belgium, 19-22 March 2019. Crit Care. 2019 Mar 19;23:72.
Habib t, Kassem Ab, Ahmed i. Early probiotics in prevent-ing ventilator-associated pneumonia after multiple trauma. Asian Journal of Pharmaceutical and Clinical Research. 2020 Jul 30;83–5.
Nazari B, Amani L, Ghaderi L, Gol MK. Effects of Probiotics on Prevalence of Ventilator-Associated Pneumonia in Mul-titrauma Patients Hospitalized in Neurosurgical Intensive Care Unit: A Randomized Clinical Trial. Trauma Mon. 2020 Nov 1;25(6):262–8.
Wang J, Ke H, Liu KX, Qu JM. Effects of exogenous probi-otics on the gut microbiota and clinical outcomes in criti-cally ill patients: A randomized controlled trial. Ann Palliat Med. 2021;10(2):1180–90.
Litton E, Anstey M, Broadhurst D, Chapman A, Currie A, Ferrier J, et al. Early and sustained Lactobacillus plantarum probiotic therapy in critical illness: the randomised, place-bo-controlled, restoration of gut microflora in critical ill-ness trial (ROCIT). Intensive Care Med. 2021 Mar 1;47(3):307–15.
Jennie Johnstone M et al. Effect of Probiotics on Incident Ventilator-Associated Pneumonia in Critically Ill Patients. JAMA. 2021;
Tsilika M, Thoma G, Aidoni Z, Tsaousi G, Fotiadis K, Stavrou G, et al. A four-probiotic preparation for ventilator-associated pneumonia in multi-trauma patients: results of a randomized clinical trial. Int J Antimicrob Agents. 2022 Jan 1;59(1).
Lu P, Li D, Tian Q, Zhang J, Zhao Z, Wang H, et al. Effect of mixed probiotics on pulmonary flora in patients with me-chanical ventilation: an exploratory randomized interven-tion study. Eur J Med Res. 2024 Sep 30;29(1):473.
Ohland CL, MacNaughton WK. Probiotic bacteria and intestinal epithelial barrier function. Am J Physiol Gastroin-test Liver Physiol. 2010;298(6).
Siempos II, Ntaidou TK, Falagas ME. Impact of the admin-istration of probiotics on the incidence of ventilator-associated pneumonia: A meta-analysis of randomized controlled trials. Crit Care Med. 2010;38(3):954–62.
Petrof EO, Dhaliwal R, Manzanares W, Johnstone J, Cook D, Heyland DK. Probiotics in the critically ill: A systematic re-view of the randomized trial evidence. Crit Care Med. 2012;40(12):3290–302.
Manzanares W, Lemieux M, Langlois PL, Wischmeyer PE. Probiotic and synbiotic therapy in critical illness: A sys-tematic review and meta-analysis. Crit Care [Inter-net].2016;20(1).Available from:
Wang B, Xie J, Teng Y. A meta-analysis of the effects of probiotics on various parameters in critically ill ventilated individuals. Advances in Clinical and Experimental Medi-cine. 2023;32(7).
Lou J, Cui S, Huang N, Jin G, Chen C, Fan Y, et al. Efficacy of probiotics or synbiotics in critically ill patients: A sys-tematic review and meta-analysis. Clin Nutr ESPEN [Inter-net]. 2024;59:48–62. Available from: https://doi.org/10.1016/j.clnesp.2023.11.003
Sun Y chen, Wang C yi, Wang H li, Yuan Y, Lu J hong, Zhong L. Probiotic in the prevention of ventilator-associated pneumonia in critically ill patients: evidence from meta-analysis and trial sequential analysis of ran-domized clinical trials. BMC Pulm Med [Internet]. 2022;22(1):1–12. Available from: https://doi.org/10.1186/s12890-022-01965-5
Li C, Liu L, Gao Z, Zhang J, Chen H, Ma S, et al. 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. Front Med (Lausanne). 2021;8(July).
Barraud D, Bollaert PE, Gibot S. Impact of the administra-tion of probiotics on mortality in critically ill adult patients: A meta-analysis of randomized controlled trials. Chest [In-ternet]. 2013;143(3):646–55. Available from: http://dx.doi.org/10.1378/chest.12-1745
Bekaert M, Timsit JF, Vansteelandt S, Depuydt P, Vésin A, Garrouste-Orgeas M, et al. Attributable mortality of venti-lator-associated pneumonia: A reappraisal using causal analysis. Am J Respir Crit Care Med. 2011;184(10):1133–9.
Alexandre Y, Le Blay G, Boisramé-Gastrin S, Le Gall F, Héry-Arnaud G, Gouriou S, et al. Probiotics: A new way to fight bacterial pulmonary infections? Med Mal Infect [Internet]. 2014;44(1):9–17. Available from: http://dx.doi.org/10.1016/j.medmal.2013.05.001
Goldenberg JZ, Ma SSY, Saxton JD, Martzen MR, Vandvik PO, Thorlund K, et al. Probiotics for the prevention of Clos-tridium difficile-associated diarrhea in adults and children. Cochrane Database of Systematic Reviews. 2013;2013(5).
Hempel, S. Newberry, SJ. Maher, A; Wang, Z; Miles, JN; Shanman R et al. Probiotics for the Prevention and Treat-ment Diarrhea, Antibiotic-associated. JAMA. 2012;307(18):1959–69.
Lee ZY, Lew CCH, Ortiz-Reyes A, Patel JJ, Wong YJ, Loh CTI, et al. Benefits and harm of probiotics and synbiotics in adult critically ill patients. A systematic review and meta-analysis of randomized controlled trials with trial sequen-tial analysis. Clinical Nutrition [Internet]. 2023;42(4):519–31.Available from: https://doi.org/10.1016/j.clnu.2023.01.019
Most read articles by the same author(s)