Yonsei researchers discover how gut microbes regulate gastric stem cells

Korean researchers have uncovered how gut microbes regulate the activity of gastric stem cells, which are crucial for repairing and regenerating the stomach lining. 

The findings, published in the journal Developmental Cell in December, offer new insights into the complex relationship between gut bacteria and stem cell behavior, with potential implications for treating stomach diseases.

The research, led by Professor Nam Ki-taek and Dr. Jeong Haeng-dueng from Yonsei University College of Medicine’s Department of Biomedical Science, identified that certain bacteria in the stomach produce metabolic substances, including short-chain fatty acids, which influence whether gastric stem cells remain dormant or begin to proliferate.

Unlike the small and large intestines, where microorganisms are abundant and well-studied, the stomach’s sparse microbial population has historically received less attention due to its highly acidic environment.

However, the study found that the stomach harbors about 200 types of symbiotic microorganisms that contribute to maintaining homeostasis.

Through genomic analysis and experiments on germ-free and normal mice, the researchers observed that gastric stem cell proliferation sharply increased in germ-free mice compared to those with normal gut microbiota. This suggests that gut bacteria play a crucial role in controlling excessive cell division.

One critical bacterium identified in the study was Lactobacillus intestinalis, which produces butyrate, a short-chain fatty acid that suppresses the proliferation of gastric stem cells. These stem cells typically remain inactive under normal conditions and are only activated during damage to the stomach lining, where they assist in repair.

The team validated their findings using lab-grown gastric organoids—simplified versions of stomach tissue derived from stem cells—and transplanted them into germ-free mice. The experiments confirmed that butyrate produced by Lactobacillus bacteria directly regulates gastric stem cell behavior, demonstrating the microbes’ essential role in maintaining stomach health.

“This study provides a critical clue to understanding how the stomach maintains its delicate balance,” Professor Nam said. He emphasized that the findings could inform the development of therapies targeting gastric diseases, potentially through interventions involving gut microbiota or their metabolic byproducts.