Roles of oral microbiome bacteria in modulating pathogenicity of Helicobacter pylori in infected population


Grant Data
Project Title
Roles of oral microbiome bacteria in modulating pathogenicity of Helicobacter pylori in infected population
Principal Investigator
Professor Huang, Shi   (Principal Investigator (PI))
Co-Investigator(s)
Professor Hung Fan Ngai Ivan   (Co-Investigator)
Duration
24
Start Date
2024-06-30
Amount
70533
Conference Title
Roles of oral microbiome bacteria in modulating pathogenicity of Helicobacter pylori in infected population
Keywords
Roles of oral microbiome bacteria in modulating pathogenicity of Helicobacter pylori in infected population
Discipline
DentistryGastroenterology/Hepatobiliary
HKU Project Code
2302101891
Grant Type
Seed Fund for PI Research – Basic Research
Funding Year
2023
Status
On-going
Objectives
Helicobacter pylori is a bacterium which infects more than half of the total world population. It is considered carcinogenic to human due to its high occurrence in gastric cancer patients. Despite its strong association with a variety of gastric diseases, disease rate is low, with only around 3% of the infected population developing gastric cancer eventually and the majority remaining asymptomatic [1–3].H. pylori can induce inflammation, interfere with host cell expression, and lower the acidity of the gastric environment[1,4]. As a result, the altered gastric environment brings about disruption to the indigenous gastric microbiome. Rather, it is believed that bacteria which later colonize the stomach (e.g., Actinobacteria, Proteobacteria, Fusobacteria, Firmicutes, and Bacteroides[3]) following the disruption of gastric environment by H. pylori are the main drivers of inflammation and subsequent development of diseases [5–7]. It has also been reported that the bacteria which later colonize the gastric environment upon H. pylori infection play a more significant role in driving the onset and progression of gastric diseases. H. pylori can undergo symbiosis with Candida albicans and Streptococcus mutans to increase survival[2,8].Although H. pylori is quite adequately studied, challenges in infection management and antibiotic resistance persist. Given that most of the individuals infected by H. pylori are not symptomatic, and that the gastric microbiome is strongly linked to disease progression, it is crucial to study the infection and pathogenicity of H. pylori in the context of microbiome[2,5,9]. By understanding the relationship between oral-gastric microbiome transmission, pathogenicity of H. pylori, and the various degrees of susceptibility to gastric diseases among H. pylori-infected individuals, this study may provide insights to alternative treatments for H. pylori-associated gastric diseases to the current the eradication practice (such as PPI), which fails to guarantee clearance of H. pylori or subsequent protection against gastric diseases.Hypothesis: Healthy carriers of H. pylori harbor distinct oral and stomach microbiomes, in which pathogenicity of H. pylori is suppressed, from those of patients of H. pylori-associated gastric disorders, and from those of H. pylori-negative healthy controls.Objectives:Analyze variations in the composition of oral and gastric microbiomes between diseased and asymptomatic H. pylori-infected individuals using available 16S sequencing and metagenomics databasesIdentify and compare with existing literatures the key bacterial markers distinguishing diseased and asymptomatic oral and gastric microbiomes among H. pylori-infected individualsEvaluate the significance of oral-gastric microbiome transmission in the colonization of stomach by different oral bacteria in diseased and asymptomatic microbiomes, potentially leading to the different outcomes after H. pylori-infectionInvestigate the effects of individual and combinations of the identified oral bacteria in (2) on the behavior and pathogenicity of H. pylori via in vitro assaysAssociate experimental results in (4) with the microbiome metadata to provide possible explanations of the observed different fates of H. pylori infectionReferencesSchistosomes, liver flukes and Helicobacter pylori. IARC Monogr Eval Carcinog Risks Hum. 1994;61:1-241. PMID: 7715068; PMCID: PMC7681621.Elghannam MT, Hassanien MH, Ameen YA, Turky EA, ELattar GM, ELRay AA, ELTalkawy MD. Helicobacter pylori and oral-gut microbiome: clinical implications. Infection. 2023 Nov 2. doi: 10.1007/s15010-023-02115-7. Epub ahead of print. PMID: 37917397.Bakhti SZ, Latifi-Navid S. Interplay and cooperation of Helicobacter pylori and gut microbiota in gastric carcinogenesis. BMC Microbiol. 2021 Sep 23;21(1):258. doi: 10.1186/s12866-021-02315-x. PMID: 34556055; PMCID: PMC8461988.Baj J, Forma A, Sitarz M, Portincasa P, Garruti G, Krasowska D, Maciejewski R. Helicobacter pylori Virulence Factors-Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment. Cells. 2020 Dec 25;10(1):27. doi: 10.3390/cells10010027. PMID: 33375694; PMCID: PMC7824444.Yu T, Lu T, Deng W, Yao D, He C, Luo P, Song J. Microbiome and function alterations in the gastric mucosa of asymptomatic patients with Helicobacter pylori infection. Helicobacter. 2023 Jun;28(3):e12965. doi: 10.1111/hel.12965. Epub 2023 Mar 8. PMID: 36890119.Ferreira RM, Pereira-Marques J, Pinto-Ribeiro I, Costa JL, Carneiro F, Machado JC, Figueiredo C. Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota. Gut. 2018 Feb;67(2):226-236. doi: 10.1136/gutjnl-2017-314205. Epub 2017 Nov 4. PMID: 29102920; PMCID: PMC5868293.Sung JJY, Coker OO, Chu E, Szeto CH, Luk STY, Lau HCH, Yu J. Gastric microbes associated with gastric inflammation, atrophy and intestinal metaplasia 1 year after Helicobacter pylori eradication. Gut. 2020 Sep;69(9):1572-1580. doi: 10.1136/gutjnl-2019-319826. Epub 2020 Jan 23. PMID: 31974133; PMCID: PMC7456733.d'Enfert C, Kaune AK, Alaban LR, Chakraborty S, Cole N, Delavy M, Kosmala D, Marsaux B, Fróis-Martins R, Morelli M, Rosati D, Valentine M, Xie Z, Emritloll Y, Warn PA, Bequet F, Bougnoux ME, Bornes S, Gresnigt MS, Hube B, Jacobsen ID, Legrand M, Leibundgut-Landmann S, Manichanh C, Munro CA, Netea MG, Queiroz K, Roget K, Thomas V, Thoral C, Van den Abbeele P, Walker AW, Brown AJP. The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives. FEMS Microbiol Rev. 2021 May 5;45(3):fuaa060. doi: 10.1093/femsre/fuaa060. PMID: 33232448; PMCID: PMC8100220.Graham DY. Helicobacter pylori update: gastric cancer, reliable therapy, and possible benefits. Gastroenterology. 2015 Apr;148(4):719-31.e3. doi: 10.1053/j.gastro.2015.01.040. Epub 2015 Feb 2. PMID: 25655557; PMCID: PMC4375058.Li Y, Hu Y, Zhan X, Song Y, Xu M, Wang S, Huang X, Xu ZZ. Meta-analysis reveals Helicobacter pylori mutual exclusivity and reproducible gastric microbiome alterations during gastric carcinoma progression. Gut Microbes. 2023 Jan-Dec;15(1):2197835. doi: 10.1080/19490976.2023.2197835. PMID: 37020297; PMCID: PMC10078126.