As a recognized pathogen, Helicobacter pylori can cause chronic gastritis, peptic ulcers, and gastric cancer. More than 50% of the world’s population is infected with this stomach bacterium. Studies have shown that disease severity in infected patients is related to the amount of H. pylori in the body. Currently, the conventional therapeutic option is triple therapy or bismuth-containing quadruple therapy, as recommended by the Maastriacht IV/Florence Consensus Report, which has a 10-day treatment eradication rate of over 90%. In addition to antibiotic therapy, there are many dietary treatments and Lactobacillus bacteria supplement therapy for H. pylori infection. Co-aggregation of Lactobacillus bacteria and pathogenic bacteria is described as the process by which genetically distinct bacteria are linked to each other by specific molecules. In disease states, specific co-aggregation as a means of restoring homeostasis has been widely discussed. Many studies have reported that Lactobacillus can prevent the development of pathogenic biofilms by co-aggregating pathogenic bacteria in the mouth, vagina, and gastrointestinal tract, thus alleviating the development of disease. To date, some studies have shown that reducing the load of H. pylori in the stomach via selective bacterial-bacterial cell interaction is a neoteric and efficient method against H. pylori infection. In this study, an in vitro screening model was constructed to evaluate the co-aggregation of 56 Lactobacillus strains with H. pylori, and the structural composition of the aggregates was observed by scanning electron microscope (SEM) and confocal laser scanning microscope (CLSM). These Lactobacillus strains, collected by the Biotechnology Center, School of Food Science and Technology, Jiangnan University, came from wild-type strains of diverse origins, such as food sources or the gut flora of long-lived people. Then the effects of the time, temperature, pH, incubation speed, ultrasonic and surface hydrophobicity on the aggregation were further investigated. Due to the low pH of the human stomach and the peristalsis associated with digestion, these factors were considered in this study to evaluate Lactobacillus with the ability to co-aggregate H. pylori. Finally, a comparative genomics approach was used to analyze the differences of functional genes in strains with different aggregating abilities. The results showed that the co-aggregation ability of Lactobacillus and H. pylori was different between strains. Among them, Lactobacillus kitasatonis Guxi82GMM and Lactobacillus reuteri 984 had better co-aggregation effect, and their co-aggregation rate could reach 42%-59% within 10 min. There was a significant correlation between the co-aggregation rate and pH value and surface hydrophobicity of strain, but was not related to temperature, incubation speed and ultrasonic treatment. In addition, there were significant differences in amino acid expression levels among strains with different co-aggregative abilities, suggesting that the material basis of the co-aggregation of Lactobacillus and H. pylori might be surface protein on Lactobacillus. Therefore, the co-aggregation of Lactobacillus and H. pylori can occur rapidly and stably in the human stomach. The selected Lactobacillus can combine to the dissociative H. pylori surface through some specific surface components (such as surface proteins), and form larger aggregates to promote the elimination of pathogenic bacteria from the body. The co-aggregation ability of Lactobacillus and H. pylori is an effective way for targeted screening probiotics to alleviate H. pylori infection.
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