| 1.BackgroundThe stomach is an important digestive organ of the human body.Gastritis is the most common disease of digestive system disease in clinic.There are about a 120million patients with gastroenteritis in China.Every year,,and acute gastroenteritis cases reach 748 million people(0.56 times/person year).The incidence rate of chronic gastritis is as high as 30%,which seriously affects people’s production and life.The causes of gastritis include Helicobacter pylori(H.pylori,HP)infection,drugs,alcohol,stress,and so on.The removal of damage factors is particularly important in the prevention and treatment of gastritis.Traditional treatment(H.pylori infection adopts bismuth-containing quadruple therapy(PPI,bismuth agent,and two antibiotics)resulted in increased drug resistance while the treatment effect was not obvious.At the same time,antibiotics can cause gastrointestinal dysfunction and intestinal flora disorder.Long-term use of PPI drugs can increase the risk of fracture and pneumonia.Therefore,it is a hot research topic to develop safe and effective preparations or methods to antagonize and inhibit gastric inflammation and restore the homeostasis of gastric flora.Microecological therapy brings new ideas to the treatment of gastric diseases.A large number of studies have shown that probiotics have a certain therapeutic effect on gastric diseases.Lactobacillus has been widely studied for its probiotic properties,safety and antagonistic effect against H.pylori.However,the existing probiotics mainly come from feces or dairy products,which is difficult to tolerate gastric acid colonization in the stomach,so the effect is unstable.Moreover,the current research mainly focuses on foreign strains such as LGG,and the lack of effective strains with independent intellectual property rights is a big problem.Probiotics derived from human gastric mucosa naturally possess the characteristics of gastric tissue colonization and gastric acid tolerance,so they have great potential in the prevention and treatment of gastric diseases.In this study,we will isolate Lactobacillus from the gastric mucosa of healthy adults,and screen out lactobacillus with the potential of inhibiting H.pylori and preventing and treating gastric diseases through multiple evaluation.And we will study the preventive and therapeutic effects of human gastro-derived Lactobacillus on gastritis.2.Methods(1)Isolation and identification of human gastro-derived probiotics:The gastric mucosa tissues of healthy subjects were collected by electronic gastroscopy,and lactobacillus was isolated and cultured by traditional culture medium.The strains were identified by biochemical experiments and 16S rRNA.(2)Screening of human gastroderived probiotics:Lactobacillus isolated was comprehensively evaluated by acid tolerance test,bile salt tolerance test,SCFAs and LCFAs production test,adhesion ability of gastric epithelial cells and in vivo imaging,and potential Lactobacillus was screened out.In vitro bacteriostatic experiments were used to screen the strains with the most potential to prevent and treat gastric diseases.(3)Effect evaluation of Human Gastro-derived Lactobacillus on chronic gastritis caused by H.pylori:Chronic gastritis model was established by h.pylori infected mice,and then the effect of human gastroderived Lactobacillus on chronic gastritis was evaluated and its mechanism was preliminarily discussed.(4)Effect evaluation of human gastro-derived Lactobacillus on alcohol refined acute hemorrhagic erosive gastritis:Alcohol was used to establish a mouse model of acute hemorrhagic erosive gastritis in Kunming mice,and the gastroprotective effects of human gastro-derived Lactobacillus on acute gastritis was explored.3.Results(1)716 strains of bacteria were isolated from 97 healthy gastric mucosa samples,including 24 strains of 12 strains of those were included in this study.(2)Four potential strains of LG-4、LG-6、LG-7 and LP-1 were screened by prebiotic evaluation.(3)The strain LG-7 was screened to effectively inhibit the growth of down-regulate the virulence gene of CagA,and reduce the cell inflammation caused by.(4)The C57BL/6 mouse model of gastritis infected with H.pylori was successfully established.After the intervention of gastric LG-7,the symptoms of inflammatory cell infiltration can be significantly alleviated and the homeostasis of gastric flora can be restored.(5)LG-7 can effectively prevent acute hemorrhagic erosive gastritis,and LG-7 significantly reduces mucosal damage in ethanol-derived acute erosive hemorrhagic gastritis.4.Conclusion(1)Four strains of human gastro-derived lactobacillus that can tolerate artificial gastric juice lower than PH=3 and can be implanted in the stomach for more than 72h were selected.These lactobacillus has the potential to treat gastro-related diseases.(2)Human gastric-derived LG-7 can effectively inhibit and induce chronic gastritis and restore the homeostasis of microecology of gastric flora.(3)Human gastric-derived LG-7 has a significant Gastroprotective effects in preventing acute erosive hemorrhagic gastritis caused by alcohol... |
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