Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2015; 21(21): 6561-6571
Published online Jun 7, 2015. doi: 10.3748/wjg.v21.i21.6561
Probiotic BIFICO cocktail ameliorates Helicobacter pylori induced gastritis
Hong-Jing Yu, Wei Liu, Zhen Chang, Hui Shen, Li-Juan He, Sha-Sha Wang, Lu Liu, Yuan-Ying Jiang, Guo-Tong Xu, Mao-Mao An, Jun-Dong Zhang
Hong-Jing Yu, Zhen Chang, Sha-Sha Wang, Lu Liu, Jun-Dong Zhang, Shanghai Sine Pharmaceutical Laboratories Co, Ltd, Shanghai 201206, China
Hong-Jing Yu, School of Pharmacy, Shanghai Jiaotong University, Shanghai 200240, China
Wei Liu, Hui Shen, Li-Juan He, Yuan-Ying Jiang, Guo-Tong Xu, Mao-Mao An, Jun-Dong Zhang, Department of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200092, China
Yuan-Ying Jiang, New Drug Research and Development Center, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
Author contributions: Yu HJ and Liu W contributed equally to this work; An MM is co-corresponding author of this article; Liu W, Shen H, He LJ, Wang SS and Liu L performed the research; Chang Z, Jiang YY and Xu GT contributed essential reagents and tools; Yu HJ, An MM and Zhang JD designed the research study; Yu HJ and Liu W wrote and revised the paper.
Supported by National Natural Science Foundation of China, No. 81274164; Shanghai Manufacture-Education-Research-Medical Cooperative Project, No 12DZ1930505.
Ethics approval: The study was reviewed and approved by the Tongji University School of Medicine Institutional Review Board.
Institutional animal care and use committee: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Tongji University School of Medicine (IACUC protocol number: TJLAC-014-012).
Conflict-of-interest: The authors declare that there is no conflict of interests regarding the publication of this article.
Data sharing: Technical appendix, statistical code, and dataset available from the corresponding author at Zhangjd534@163.com. Participants gave informed consent for data sharing. No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Jun-Dong Zhang, MD, Department of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 1239 Siping Road, Shanghai 200092, China. zhangjd534@163.com
Telephone: +86-21-65988562 Fax: +86-21-95988562
Received: November 30, 2014
Peer-review started: December 1, 2014
First decision: January 8, 2015
Revised: February 5, 2015
Accepted: March 12, 2015
Article in press: March 12, 2015
Published online: June 7, 2015
Processing time: 192 Days and 17.6 Hours
Abstract

AIM: To determine the protective effect of triple viable probiotics on gastritis induced by Helicobacter pylori (H. pylori) and elucidate the possible mechanisms of protection.

METHODS: Colonization of BIFICO strains in the mouse stomach was determined by counting colony-forming units per gram of stomach tissue. After treatment with or without BIFICO, inflammation and H. pylori colonization in the mouse stomach were analyzed by hematoxylin and eosin and Giemsa staining, respectively. Cytokine levels were determined by enzyme-linked immunosorbent assay and Milliplex. The activation of nuclear factor (NF)-κB and MAPK signaling in human gastric epithelial cells was evaluated by Western blot analysis. Quantitative reverse transcription-polymerase chain reaction was used to quantify TLR2, TLR4 and MyD88 mRNA expression in the mouse stomach.

RESULTS: We demonstrated that BIFICO, which contains a mixture of Enterococcus faecalis, Bifidobacterium longum and Lactobacillus acidophilus, was tolerant to the mouse stomach environment and was able to survive both the 8-h and 3-d courses of administration. Although BIFICO treatment had no effect on the colonization of H. pylori in the mouse stomach, it ameliorated H. pylori-induced gastritis by significantly inhibiting the expression of cytokines and chemokines such as TNF-α, IL-1β, IL-10, IL-6, G-CSF and MIP-2 (P < 0.05). These results led us to hypothesize that BIFICO treatment would diminish the H. pylori-induced inflammatory response in gastric mucosal epithelial cells in vitro via the NF-κB and MAPK signaling pathways. Indeed, we observed a decrease in the expression of the NF-κB subunit p65 and in the phosphorylation of IκB-α, ERK and p38. Moreover, there was a significant decrease in the production of IL-8, TNF-α, G-CSF and GM-CSF (P < 0.05), and the increased expression of TLR2, TLR4 and MyD88 induced by H. pylori in the stomach was also significantly reduced following BIFICO treatment (P < 0.05).

CONCLUSION: Our results suggest that the probiotic cocktail BIFICO can ameliorate H. pylori-induced gastritis by inhibiting the inflammatory response in gastric epithelial cells.

Keywords: BIFICO; Gastritis; Helicobacter pylori; Nuclear factor-κB; Inflammation; Toll-like receptors; Bifidobacterium longum; MAPK

Core tip: We investigated the effects of a traditional probiotic pharmaceutical cocktail in China, composed of the viable bacteria Enterococcus faecalis, Bifidobacterium longum and Lactobacillus acidophilus, on Helicobacter pylori (H. pylori)-induced gastritis in experimental mice and found that it could ameliorate H. pylori-induced gastritis by inhibiting the epithelial cell inflammatory response.