How do Lactobacilli treat Helicobacter pylori-related diseases?

Some studies have demonstrated H. pylori stimulates the release of interleukin-8 (IL-8) from gastric epithelia, which initiates inflammatory damage to gastric mucosa and plays a crucial role in the pathogenesis of H. pylori infections. H. pylori lipopolysaccharide (H. pylori-LPS) is the major initiator in H. pylori-induced IL-8 production via activation of Toll-like receptor 4 (TLR4) pathway in gastric epithelia. Considering the novel finding that H. pylori is an indigenous biota in gastric microflora including Lactobacilli and hypothesis that the disturbance of gastric microecosystem plays a more important role in pathogenetic mechanisms of H. pylori, the eradiation of H. pylori doesn't seem justified to everyone. The speculation on validity of restoration of the gastric microecosystem has been demonstrated by therapeutic effects of Lactobacilli administration on H. pylori-associated diseases. But whether Lactobacilli inhibit H. pylori-LPS-induced IL-8 production through blocking H. pylori-LPS-activated TLR4 pathway hasn't been well researched.

A research article to be published on August 28, 2008 in the World Journal of Gastroenterology addresses this question. The research team led by Prof. Hong-Sheng Ma from West China Hospital of Sichuan University treated SGC-7901 cells with H. pylori Sydney strain 1 lipopolysaccharide (H. pyloriSS1-LPS) in the absence or presence of a pretreatment with viable Lactobacillus bulgaricus (LBG). The results indicated that viable LBG prevented H. pyloriSS1-LPS-activated TLR4 pathway in SGC-7901 cells, leading to its inhibitory effect on IL-8 production stimulated by H. pyloriSS1-LPS. Considering some evidence implied that supernatant recovered from Lactobacilli culture MRS broth contained some latent soluble proteins secreted by Lactobacilli, SGC-7901 cells were treated with H. pyloriSS1-LPS in the absence or presence of a pretreatment with supernatant recovered from LBG culture MRS broth (LBG-S). It was demonstrated that LBG-S had the same inhibitory effect on H. pyloriSS1-LPS-activated TLR4 signaling transduction as viable LBG. In a recent novel study, two soluble proteins with molecular sizes of 75 and 40 kDa were purified from supernatant recovered from Lactobacillus rhamnosus GG culture MRS broth and named p75 and p40 respectively, which ameliorated apoptosis of intestinal epithelia treated with tumor necrosis factor α, interferon-γ or IL-1α and promoted cell growth through activating Akt and blocking p38 mitogen-activated protein kinase and stress-activated protein kinase/c-Jun amino-terminal kinase signaling. So LBG-S in this experiment probably contained the similar or even same proteins, which could intervene in H. pyloriSS1-LPS-activated TLR4 signaling through modulating other pathways in SGC-7901 cells.

This evaluation of LBG as a probiotic model revealed an important and novel relationship between H. pylori-LPS-activated TLR4 signaling and selective microflora. This report adds to our understanding of the signal pathways in the gastric epithelia involved in inflammatory responses that are regulated by probiotics and pathogenic bacteria composing the gastric microecosystem. Further studies of the soluble components secreted by Lactobacilli may benefit to the exploration of new drugs against H. pylori-associated diseases in the future.

Reference: Zhou C, Ma FZ, Deng XJ, Yuan H, Ma HS. Lactobacilli inhibit interleukin-8 production induced by Helicobacter pylori lipopolysaccharide-activated Toll-like receptor 4. World J Gastroenterol 2008; 14(32): 5090-5095
http://www.wjgnet.com/1007-9327/14/5090.asp

Correspondence to: Hong-Sheng Ma, Department of Gastroenterology, West China Hospital of Sichuan University, 37 Guoxue Alley, Chengdu 610041, Sichuan Province, China. mhswch@163.com
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World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H. pylori infection. It provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th of every month. The WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the title China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.

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