Randomized Clinical Trial
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Mar 27, 2022; 14(3): 634-646
Published online Mar 27, 2022. doi: 10.4254/wjh.v14.i3.634
Effect of a specific Escherichia coli Nissle 1917 strain on minimal/mild hepatic encephalopathy treatment
Elina Manzhalii, Valentyna Moyseyenko, Vitalii Kondratiuk, Nataliia Molochek, Tetyana Falalyeyeva, Nazarii Kobyliak
Elina Manzhalii, Valentyna Moyseyenko, Vitalii Kondratiuk, Department of Propedeutics of Internal Medicine, Bogomolets National Medical University, Kyiv 01601, Ukraine
Nataliia Molochek, Tetyana Falalyeyeva, Educational and Scientific Centre “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv, Kyiv 01601, Ukraine
Nataliia Molochek, Department of Pediatrics, Bogomolets National Medical University, Kyiv 01601, Ukraine
Tetyana Falalyeyeva, Nazarii Kobyliak, Department of Scientific, Medical Laboratory CSD, Kyiv 01004, Ukraine
Nazarii Kobyliak, Department of Endocrinology, Bogomolets National Medical University, Kyiv 01601, Ukraine
Author contributions: Manzhalii E, Moyseyenko V and Kondratiuk V were responsible for the study conception and design, data analysis and interpretation, and manuscript drafting; Molochek N, Falalyeyeva T and Kobyliak N critically revised the article for important intellectual content; all the authors reviewed and approved the final version to be published.
Institutional review board statement: The study protocol was approved by the Ethics Committee at Bogomolets National Medical University (protocol number: 106/2017).
Clinical trial registration statement: The study protocol was registered in Clinical.Trial.gov database under the entry number NCT04787276.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All authors declare no potential conflicting interests related to this paper.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Nazarii Kobyliak, PhD, Associate Professor, Department of Endocrinology, Bogomolets National Medical University, Pushkinska 22 Street, Kyiv 01601, Ukraine. nazariikobyliak@gmail.com
Received: March 31, 2021
Peer-review started: March 31, 2021
First decision: July 27, 2021
Revised: August 1, 2021
Accepted: February 22, 2022
Article in press: February 22, 2022
Published online: March 27, 2022
Processing time: 357 Days and 17.1 Hours
Abstract
BACKGROUND

Hepatic encephalopathy (HE) can be considered a result of dysregulated gut-liver-brain axis function, where cognitive impairment can be reversed or prevented by the beneficial effects induced by "gut-centric" therapies, such as the administration of nonabsorbable disaccharides, nonabsorbable antibiotics, probiotics and prebiotics.

AIM

To assess the short-term efficacy and safety of the probiotic Escherichia coli Nissle (EcN) 1917 strain compared to lactulose and rifaximin in patients with minimal/mild HE.

METHODS

From January 2017 to March 2020, a total of 45 patients with HE were enrolled in this prospective, single-centre, open-label, randomized study. Participants were randomly assigned at a ratio of 1:1:1 to one of the treatment groups: The EcN group (n = 15), lactulose group (n = 15) or rifaximin group (n = 15) for a 1 mo intervention period. The main primary outcomes of the study were changes in serum ammonia and Stroop test score. The secondary outcomes were markers of a chronic systemic inflammatory response (ІL-6, ІL-8, and IFN-γ) and bacteriology of the stool flora evaluated by specialized nonculture techniques after a 1 mo intervention period.

RESULTS

Patients who were given rifaximin or EcN showed a more significant reduction in serum ammonia and normalization of Bifidobacteria and Lactobacilli abundance compared to the lactulose group. However, the most pronounced restoration of the symbiotic microflora was associated with EcN administration and characterized by the absence of E. coli with altered properties and pathogenic enterobacteria in patient faeces. In the primary outcome analysis, improvements in the Stroop test parameters in all intervention groups were observed. Moreover, EcN-treated patients performed 15% faster on the Stroop test than the lactulose group patients (P = 0.017). Both EcN and rifaximin produced similar significant reductions in the proinflammatory cytokines INF-γ, IL-6 and IL-8. EcN was more efficient than lactulose in reducing proinflammatory cytokine levels.

CONCLUSION

The use of the probiotic EcN strain was safe and quite efficient for HE treatment. The probiotic reduced the ammonia content and the level of serum proinflammatory cytokines, normalized the gut microbiota composition and improved the cognitive function of patients with HE. The application of the EcN strain was more effective than lactulose treatment.

Keywords: Hepatic encephalopathy; Chronic liver disease; cirrhosis; Gut microbiota; E. coli Nissle 1917; Cognitive functions; Stroop test; Rifaximin; Lactulose

Core Tip: In a prospective, single-centre, open-label, randomized study, the short-term efficacy and safety of Escherichia coli Nissle (EcN) 1917 compared to that of lactulose and rifaximin in patients with hepatic encephalopathy were evaluated. The probiotic reduced the ammonia content and the level of serum proinflammatory cytokines, normalized the gut microbiota composition and improved the cognitive functions of patients with hepatic encephalopathy. The application of the EcN strain was more effective than lactulose treatment.