Grant: Alliance Grants

Helicobacter pylori (HP) colonizes chronically ~50% of the world's population. While it may be considered part of the normal gut flora, it can cause gastric tissue inflammation and gastric ulcers or cancers in a small fraction of colonized people. We propose that its ability to cause disease unleashes when normal stomach physiology is disturbed, leading to HP proliferation and production of inflammatory factors that causes further physiological dysregulation. Our partner and others have shown that ingesting Lactic Acid Bacteria (LAB) can safely enhance the treatment of HP infections, prevent infection and/or improve gut health. We propose that the probiotic LAB or their components indirectly help maintain optimal gastric physiology via their direct effects on HP. We have already shown that LAB produce and release secretions that decrease HP's viability and repress the physiological HP-induced production of pro-inflammatory molecules. The challenge is now to understand how the LAB secretions exert these effects at the molecular level. We are focusing on characterizing the active molecules and determining how they are sensed by HP and how they modulate its ability to affect gastric physiology. While the work is mechanistic in nature, in the long term, it can be exploited to derive new therapeutic agents to aid in HP infection management, as needed in light of rising antibiotic resistance. This work will eventually benefit ~6 million new gastric ulcers or cancers patients per year worldwide and will alleviate the economic burden of health care costs associated with these diseases.