Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Nutrition and Health (including climate and ecological aspects)

Effect of early enteral nutrition combined with probiotics in patients with stroke: a meta-analysis of randomized controlled trials

European Journal of Clinical Nutrition volume 76, pages 592–603 (2022)Cite this article

Subjects

Abstract

Background/Objectives

Whether to conduct early enteral nutrition combined with probiotics (EEN/probiotics) in stroke patients remains controversial. This study was aimed to systematically explore the efficacy and safety of EEN/probiotics in stroke patients.

Subject/Methods

We performed searches in EMBASE, PubMed, Medline, Cochrane Library, Chinese Biomedicine Literature Database (SinoMed), Chinese Scientific Journal Database (VIP), Chinese National Knowledge Infrastructure (CNKI) and Wanfang database.

Results

A total of 26 randomized controlled trials (2216 patients) were included. Meta-analysis showed a significantly lower incidence of gastrointestinal complications (%) (OR, 0.29; 95% CI,0.24–0.36; P < 0.00001), a lower incidence of infection (%) (OR, 0.27; 95% CI, 0.21–0.36; P < 0.00001), a shorter length of hospital stay (d) (MD, −8.70; 95% CI, −13.24 to −4.16; P = 0.003), and a lower dysbacteriosis rate (%) (OR, 0.17; 95% CI, 0.07–0.41; P < 0.0001) in the EEN/probiotics group than EEN group. Compared with EEN group, EEN/probiotics group had lower levels of diamine oxidase (U/L) (MD, −0.78; 95% CI, −0.93 to −0.63; P < 0.00001), D-lactic acid (mmol/L) (MD, −0.06; 95% CI, −0.07 to −0.05; P < 0.00001) and higher levels of albumin (g/L) (MD, 3.38; 95% CI, 2.74–4.02; P < 0.00001), prealbumin (mg/L) (MD, 32.20; 95% CI, 24.42–39.98; P < 0.00001), total protein (g/L) (MD, 4.91; 95% CI, 3.20–6.62; P < 0.00001), hemoglobin (g/L) (MD, 9.62; 95% CI, 7.92–11.32; P < 0.00001), immunoglobulin A (g/L) (MD, 0.23; 95% CI, 0.12–0.34; P < 0.0001) and immunoglobulin G (g/L) (MD, 0.33; 95% CI, 0.21–0.45; P < 0.00001).

Conclusion

Early enteral nutrition combined with probiotics may effectively improve the nutritional status of stroke patients, regulate the intestinal flora and intestinal mucosal barrier function, improve the immune function, reduce the incidence of infectious complications and gastrointestinal motility disorders.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2: Risk of bias assessment based on review author’s judgment about a risk of bias item for each eligible study (n = 26).
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Hatano S. Experience from a multicentre stroke register: a preliminary report. Bull World Health Organ. 1976;54:541–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Strong K, Mathers C, Bonita R. Preventing stroke: saving lives around the world. Lancet Neurol. 2007;6:182–7. https://doi.org/10.1016/S1474-4422(07)70031-5.

    Article  PubMed  Google Scholar 

  3. Kim BR, Lee J, Sohn MK, Kim DY, Lee SG, Shin YI, et al. Risk factors and functional impact of medical complications in stroke. Ann Rehabil Med. 2017;41:753–60. https://doi.org/10.5535/arm.2017.41.5.753.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Xu CY, Ye HW, Chen B, Wu YF, Cao Z, Ding Z, et al. Analysis of risk factors and prognosis of post-stroke pulmonary infection in integrated ICU. Eur Rev Med Pharm Sci. 2021;25:856–65. https://doi.org/10.26355/eurrev_202101_24654.

    Article  Google Scholar 

  5. Li X, Wang L, Zhao B, Mei D, Jiang J. Enteral nutrition bibliometry from 2010 to 2019. Asia Pac J Clin Nutr. 2020;29:681–9. https://doi.org/10.6133/apjcn.202012_29(4).0002.

    Article  PubMed  Google Scholar 

  6. Sheng L, Yin L, Peng D, Zhao L. From best evidence to best practice: enteral nutrition from continuous nasal feeding in stroke patients. Int J Gen Med. 2020;13:927–36. https://doi.org/10.2147/IJGM.S269393.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Yuan MZ, Li F, Fang Q, Wang W, Peng JJ, Qin DY, et al. Research on the cause of death for severe stroke patients. J Clin Nurs. 2018;27:450–60. https://doi.org/10.1111/jocn.13954.

    Article  PubMed  Google Scholar 

  8. Mi H, Li S, Li H, Hu W. The effects of infection on severe stroke patients in the neurological intensive care unit in China. Int J Neurosci. 2018;128:715–20. https://doi.org/10.1080/00207454.2017.1412966.

    Article  PubMed  Google Scholar 

  9. Lieber AC, Hong E, Putrino D, Nistal DA, Pan JS, Kellner CP. Nutrition, energy expenditure, dysphagia, and self-efficacy in stroke rehabilitation: a review of the literature. Brain Sci. 2018;8:218. https://doi.org/10.3390/brainsci8120218.

    Article  CAS  PubMed Central  Google Scholar 

  10. Zhao D, Qin HL, Li N. [Integrated strategy based on microecological therapy in the treatment of inflammatory bowel disease]. Zhonghua Wei Chang Wai Ke Za Zhi. 2020;23:38–44. https://doi.org/10.3760/cma.j.cn.441530-20200414-00205.

    Article  CAS  PubMed  Google Scholar 

  11. Cunningham M, Azcarate-Peril MA, Barnard A, Benoit V, Grimaldi R, Guyonnet D, et al. Shaping the future of probiotics and prebiotics. Trends Microbiol. 2021;S0966-842X:00005–6. https://doi.org/10.1016/j.tim.2021.01.003.

    Article  CAS  Google Scholar 

  12. Du T, Jing X, Song S, Lu S, Xu L, Tong X, et al. Therapeutic effect of enteral nutrition supplemented with probiotics in the treatment of severe craniocerebral. Injury: A Syst Rev Meta-Anal World Neurosurg. 2020;139:e553–71. https://doi.org/10.1016/j.wneu.2020.04.083.

    Article  Google Scholar 

  13. Yi LJ, Tian X, Shi B, Pi YP, Chen WQ. Early enteral nutrition supplemented with probiotics improved the clinical outcomes in severe head injury: some promising findings from Chinese patients. Medicine. 2019;98:e15426. https://doi.org/10.1097/MD.0000000000015426.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Gu WJ, Deng T, Gong YZ, Jing R, Liu JC. The effects of probiotics in early enteral nutrition on the outcomes of trauma: a meta-analysis of randomized controlled trials. JPEN J Parenter Enter Nutr. 2013;37:310–7. https://doi.org/10.1177/0148607112463245.

    Article  CAS  Google Scholar 

  15. Page MJ, Moher D. Evaluations of the uptake and impact of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Statement and extensions: a scoping review. Syst Rev. 2017;6:263. https://doi.org/10.1186/s13643-017-0663-8.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Wang XD. Diagnosis points of various cerebrovascular diseases[J]. Chin J Neurol. 1996;029:379–80.

    Google Scholar 

  17. Higgins J. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1. The Cochrane Collaboration[J]. Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie, 2008;5:S38.

  18. Veroniki AA, Jackson D, Viechtbauer W, Bender R, Bowden J, Knapp G, et al. Methods to estimate the between-study variance and its uncertainty in meta-analysis. Res Synth. Methods. 2016;7:55–79. https://doi.org/10.1002/jrsm.1164.

    Article  Google Scholar 

  19. Wang J, Ru R, Sun J, Mi XC, Dong ZH, Liu YF, et al. Effects of Enteral Nutrition Combined with Probiotics on Nutritional Status in Patients with Acute Ischemic Stroke After Neural Intervention Therapy[J]. J Chengdu Med Coll. 2021;16:29–32. CNKI:SUN:CDYU.0.2021-01-007.

    CAS  Google Scholar 

  20. Dong GH. Clinical effect of probiotics combined with enteral nutrition in the treatment of patients with severe stroke[J]. Chin Remedies Clin. 2020;20:1687–8. CNKI:SUN:YWLC.0.2020-10-052.

    Google Scholar 

  21. He XH, Li L, Ma XW. Effect of bifidobacterium combined with enteral nutrition on nutrition, immunity and intestinal flora in patients with severe stroke[J]. China Health Care Nutr. 2020;30:75.

    Google Scholar 

  22. Xie YM. Effect of early enteral nutrition combined with probiotics on nutritional status and gastrointestinal function of stroke patients with nasal feeding[J]. J North Pharm. 2020;17:44–45+52. CNKI:SUN:BFYX.0.2020-09-015.

    Google Scholar 

  23. Zhang L. Effect of early enteral nutrition combined with microecological preparation on patients with dysphagia after stroke and its effect on nutrition indexes[J]. Chin Foreign Med Res. 2020;18:170–2. https://doi.org/10.14033/j.cnki.cfmr.2020.14.070

    Article  Google Scholar 

  24. Ban BX, Sun ZG, Jin J. Influence of Probiotics combined with Enteral Nutrition on Nutritional Status and Complications in Acute Stroke Pa-tients with Type 2 Diabetes[J]. J Med Theory Pract. 2019;32:3588–90. https://doi.org/10.19381/j.issn.1001-7585.2019.22.003.

    Article  Google Scholar 

  25. Chen JQ. Effect of Bifidobacterium Tetravaccine tablets combined with enteral nutrition on gastrointestinal complications and intestinal mucosal barrier function in patients with severe stroke[J]. Med Forum. 2019;23:2397–8. https://doi.org/10.19435/j.1672-1721.2019.17.018.

    Article  Google Scholar 

  26. Chen JY, Luo YY, Zhu ZP, Zhu BH, Fu P. Effects of early enteral nutrition combined with probiotics on intestinal flora and immune function in patients with severe ischemic stroke[J]. Chin J Integr Traditional West Med Intensive Crit Care. 2019;26:329–33. https://doi.org/10.3969/j.issn.1008-9691.2019.03.019.

    Article  Google Scholar 

  27. Chen K. Application effect analysis of probiotics combined with early indwelling gastric tube nasogastric feeding enteral nutrition support in elderly patients with severe stroke[J]. Yiyao Qianyan. 2019;9:155–6. https://doi.org/10.3969/j.issn.2095-1752.2019.02.122.

    Article  Google Scholar 

  28. Huang J, Jiang ZL. Early enteral nutrition reconstructs intestinal microecology to promote the rehabilitation of ischemic stroke[J]. Mod Digestion Intervent. 2019;24:398–401. CNKI:SUN:XDXH.0.2019-04-018.

    Google Scholar 

  29. Jin X, Shi Y, Yuan B, Wang HL, Liu HY, Chen YJ, et al. The effect of early enteral nutrition supplemented with probiotics on ventilator-associated pneumonia in patients with severe stroke[J]. Chin J Microecol. 2019;31:174–8. https://doi.org/10.13381/j.cnki.cjm.201902012.

    Article  Google Scholar 

  30. Li JH, Li JY. Effect of Bifidobacterium Tetravaccine tablets combined with enteral nutrition on gastrointestinal complications and intestinal mucosal barrier function in patients with severe stroke[J]. J China Prescr Drug. 2019;17:125–6. CNKI:SUN:ZGCF.0.2019-09-075.

    Google Scholar 

  31. Zhang HB, Lu L, Tian YN, Li Y, Zheng Q. Effect of enteral nutrition support on acute cardiogenic stroke patients with swallowing dysfunction[J]. Chin J Microecol. 2019;31:90–93. https://doi.org/10.13381/j.cnki.cjm.201901020.

    Article  Google Scholar 

  32. Gao SJ. Effect of early enteral nutrition combined with probiotics in patients with acute severe stroke[J]. China Med Eng. 2018;26:34–37. https://doi.org/10.19338/j.issn.1672-2019.2018.06.010.

    Article  Google Scholar 

  33. Gao YX. The effect of early enteral nutrition combined with Clostridium caseinate Enterococcus triunion on improving intestinal flora and nutritional index in elderly stroke patients[J]. Chin J Geriatr Care. 2018;16:65–67. CNKI:SUN:LNBJ.0.2018-02-025.

    Google Scholar 

  34. Liao P. Effect of early enteral nutrition combined with probiotics on nutritional status and gastrointestinal function of stroke patients with nasal feeding[J]. Yiyao Qianyan. 2018;8:186–7. https://doi.org/10.3969/j.issn.2095-1752.2018.28.165.

    Article  Google Scholar 

  35. Sun HC, Zhang XG, Liu Z, Wang X, Zheng YL, Jin Y, et al. Effect of Bifidobacterium Tetravaccine Tablets on intestinal function in patients with severe stroke[J]. Chin J Microecol. 2018;30:1292–6. https://doi.org/10.13381/j.cnki.cjm.201811013.

    Article  Google Scholar 

  36. Zhou Q. Effect of Bifid Triple Viable capsules combined with early enteral nutrition on nutritional status and complications in patients with severe stroke[J]. Diet Health. 2018;5:66–67. https://doi.org/10.3969/j.issn.2095-8439.2018.01.078.

    Article  Google Scholar 

  37. Dong GH. Clinical effect of probiotics combined with enteral nutrition in the treatment of patients with severe stroke[J]. Jiankang Qianyan. 2017;26:123. https://doi.org/10.3969/j.issn.9128-6509.2017.10.116.

    Article  Google Scholar 

  38. Chen CC. Clinical effect of enteral nutrition with probiotics on stroke patients[J].Journal of BingTuan. Medicine. 2016;48:15–16. CNKI:SUN:BTYU.0.2016-02-006.

    Google Scholar 

  39. Chen DY, Chen J. Effect of Bifid Triple Viable capsules combined with early enteral nutrition on nutritional status and complications in patients with severe stroke[J]. J Brain Nerv Dis. 2016;24:79–81. CNKI:SUN:LYSJ.0.2016-02-004.

    Google Scholar 

  40. Hou JH. Influence of BifidobacteriumT etravaccine Tablets Combined with Enteral Nutrition on Complications of Digestive Canal and Intestinal Mucous Membrane Barrier Function of Patients with Severe Stroke[J]. Chin J Pharmacoepidemiol. 2016;25:11–13+42. CNKI:SUN:YWLX.0.2016-01-004.

    CAS  Google Scholar 

  41. Wang Y, Shi J, Gong LY. Effect of probiotics combined with early enteral nutrition on the incidence of pulmonary infection in patients with acute severe stroke[J]. China Health Industry Development Working Committee, China Medical Education Association. 2016:415–6. https://d.wanfangdata.com.cn/conference/ChZDb25mZXJlbmNlTmV3UzIwMjEwNTIxEgc4Nzk0OTE5GghncmppMXk0OQ%3D%3D.

  42. Wu LJ, Li JP, Guo BW. Additional bifidobacteria in severe stroke patients receiving enteral nutrition[J]. Parenter Enter Nutr. 2016;23:220–2. https://doi.org/10.16151/j.1007-810x.2016.04.007.

    Article  Google Scholar 

  43. Hou JH, Zhuo JM, Zhong WG, Guan XB, Xia B. Effect of Bifidobacterium Tetravaccine tablets on nutritional status and immune indexes in patients with severe stroke[J]. Chin J Rural Med Pharm. 2016;23:6–7. https://doi.org/10.19542/j.cnki.1006-5180.2016.07.003.

    Article  Google Scholar 

  44. Bai GY. Clinical research of probiotics enteral nutrition for the treatment of critically ill patients with cerebral apoplexy[D]. Xinjiang:Xinjiang Medical University, 2014. https://doi.org/10.7666/d.D601665.

  45. Gomes F, Emery PW, Weekes CE. Risk of malnutrition is an independent predictor of mortality, length of hospital stay, and hospitalization costs in stroke patients. J Stroke Cerebrovasc Dis.2016;25:799–806. https://doi.org/10.1016/j.jstrokecerebrovasdis.

    Article  PubMed  Google Scholar 

  46. Setyopranoto I, Lestari LA, Wijayanti PM, Rochmah MA. The effects of local food-based enteral nutrition to improve nutritional status of post-stroke patients. J Neurosci Rural Pract.2021;12:204–9. https://doi.org/10.1055/s-0040-1721202.

    Article  PubMed  PubMed Central  Google Scholar 

  47. English C, MacDonald-Wicks L, Patterson A, Attia J, Hankey GJ. The role of diet in secondary stroke prevention. Lancet Neurol.2021;20:150–60. https://doi.org/10.1016/S1474-4422(20)30433-6.

    Article  PubMed  Google Scholar 

  48. Bonsack B, Jiang RH, Borlongan CV. A gut feeling about stroke reveals gut-brain axis’ active role in homeostasis and dysbiosis. J Cereb Blood Flow Metab. 2020;40:1132–4. https://doi.org/10.1177/0271678X19900037.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Sharifi-Rad J, Rodrigues CF, Stojanović-Radić Z, Dimitrijević M, Aleksić A, Neffe-Skocińska K, et al. Probiotics: Versatile Bioactive Components in Promoting Human Health. Med (Kaunas). 2020;56:433. https://doi.org/10.3390/medicina56090433.

    Article  Google Scholar 

  50. Jiang J, Chu C, Wu C, Wang C, Zhang C, Li T, et al. Efficacy of probiotics in multiple sclerosis: a systematic review of preclinical trials and meta-analysis of randomized controlled trials. Food Funct. 2021. https://doi.org/10.1039/d0fo03203d.

  51. Zhang XF, Guan XX, Tang YJ, Sun JF, Wang XK, Wang WD, et al. Clinical effects and gut microbiota changes of using probiotics, prebiotics or synbiotics in inflammatory bowel disease: a systematic review and meta-analysis. Eur J Nutr. 2021. https://doi.org/10.1007/s00394-021-02503-5.

  52. Biswasroy P, Pradhan D, Sahu DK, Sahu A, Ghosh G, Rath G. Recent advances in clinical utility of probiotics in gastrointestinal tract disorders. Curr Pharm Biotechnol. 29 Oct 2020. https://doi.org/10.2174/1389201021666201029154239. Epub ahead of print.

  53. Patejdl R, Kästner M, Kolbaske S, Wittstock M. Clinical nutrition and gastrointestinal dysfunction in critically ill stroke patients. Neurol Res. 2017;39:959–64. https://doi.org/10.1080/01616412.2017.1367545.

    Article  PubMed  Google Scholar 

  54. Prame Kumar K, Wong CH. Imbalance in the force: the dark side of the microbiota on stroke risk and progression. Curr Opin Neurobiol. 2020;62:10–16. https://doi.org/10.1016/j.conb.

    Article  CAS  PubMed  Google Scholar 

  55. Battaglini D, Pimentel-Coelho PM, Robba C, Dos Santos CC, Cruz FF, Pelosi P, et al. Gut microbiota in acute ischemic stroke: from pathophysiology to therapeutic implications. Front Neurol.2020;11:598. https://doi.org/10.3389/fneur.2020.00598.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Stanley D, Mason LJ, Mackin KE, Srikhanta YN, Lyras D, Prakash MD, et al. Translocation and dissemination of commensal bacteria in post-stroke infection. Nat Med.2016;22:1277–84. https://doi.org/10.1038/nm.4194.

    Article  CAS  PubMed  Google Scholar 

  57. Metin M, Altun A, Köylüoğlu G. The effect of probiotics on ıntestinal motility in an experimental short bowel model. Acta Cir Bras. 2020;35:e202000804. https://doi.org/10.1590/s0102-865020200080000004.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Xu H, Ma C, Zhao F, Chen P, Liu Y, Sun Z, et al. Adjunctive treatment with probiotics partially alleviates symptoms and reduces inflammation in patients with irritable bowel syndrome. Eur J Nutr. 2021;60:2553–65. https://doi.org/10.1007/s00394-020-02437-4. Epub 22 Nov 2020.

  59. Kambale RM, Nancy FI, Ngaboyeka GA, Kasengi JB, Bindels LB, Van der Linden D. Effects of probiotics and synbiotics on diarrhea in undernourished children: Systematic review with meta-analysis. Clin Nutr. 2020;S0261-5614:30701–9. https://doi.org/10.1016/j.clnu.2020.12.026.

    Article  Google Scholar 

  60. Lehtoranta L, Latvala S, Lehtinen MJ. Role of probiotics in stimulating the immune system in viral respiratory tract infections: a narrative review. Nutrients. 2020;12:3163. https://doi.org/10.3390/nu12103163.

    Article  PubMed Central  Google Scholar 

  61. Tan AH, Lim SY, Chong KK, Manap A, Hor JW, Lim JL. Probiotics for constipation in Parkinson disease: a randomized placebo-controlled study. Neurology. 2021;96:e772–82. https://doi.org/10.1212/WNL.0000000000010998.

    Article  CAS  PubMed  Google Scholar 

  62. Zhao Y, Zeng Y, Zeng D, Wang H, Zhou M, Sun N, et al. Probiotics and MicroRNA: their roles in the host-microbe interactions. Front Microbiol. 2021;11:604462. https://doi.org/10.3389/fmicb.2020.604462.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This research was supported by a program of Department of Science and Technology of Sichuan Province (No. 2021YFS0022). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Authors and Affiliations

  1. West China School of Nursing/West China Hospital, Sichuan University, Chengdu, Sichuan, China

    Xinrong Chen, Yanjie Hu, Xingzhu Yuan &  Ka Li

  2. Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China

    Jie Yang

Authors
  1. Xinrong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yanjie Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xingzhu Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jie Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ka Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: XC, YH. Data curation: XC, JY. Formal analysis: XC, XY. Project administration: KL. Resources: KL. Software: XC, YH. Supervision: KL, JY. Writing—original draft: XC, YH, XY. Writing—review and editing: KL, JY.

Corresponding author

Correspondence to Ka Li.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics statement

The need for ethics approval was waived because this was a meta-analysis and involved no people or animals.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, X., Hu, Y., Yuan, X. et al. Effect of early enteral nutrition combined with probiotics in patients with stroke: a meta-analysis of randomized controlled trials. Eur J Clin Nutr 76, 592–603 (2022). https://doi.org/10.1038/s41430-021-00986-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41430-021-00986-3

This article is cited by

Search

Advanced search

Quick links