Development of Technology for Simultaneous Analysis of Microbial and Human Genes in Intestinal Tissue

A new technology has been developed that allows researchers to simultaneously identify the location of bacteria within intestinal tissue and analyze gene expression in human intestinal cells.

Yonsei Medical Center

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The research team led by Professor Park Yurang and Instructor Jang Sooyoung from the Department of Biomedical Systems Informatics at Yonsei University College of Medicine, along with Professor Ko Hong from the Division of Pediatric Gastroenterology and Nutrition at Severance Children’s Hospital, announced on September 8 that they have developed a technology for simultaneous analysis of microbial and human gene expression within intestinal tissue. They stated that this technology enables prognosis prediction and the establishment of treatment strategies for Crohn’s disease.

The results of this study were published in the international journal "Microbiome" (IF 12.7).

Crohn’s disease is a refractory condition characterized by chronic symptoms such as bloody stools, abdominal pain, and diarrhea, caused by inflammation in the digestive tract, including the small and large intestines. If chronic inflammation is not controlled, it can lead to serious complications such as intestinal perforation and strictures.

Crohn’s disease is known to result from abnormal interactions between intestinal microbes and the human immune system. Directly confirming the interactions between intestinal microbes and the immune system at the cellular level is crucial for understanding the exact pathogenesis of Crohn’s disease and for establishing effective treatment strategies. Furthermore, accurately identifying and utilizing beneficial bacterial strains that can suppress the onset of Crohn’s disease or alleviate its symptoms could lead to the development of microbe-based therapies.

The research team developed a "microbe-human gene expression profiling pipeline" that enables simultaneous identification of bacterial locations within intestinal tissue and analysis of gene expression in human intestinal cells. This technology detects both RNA (ribonucleic acid) expression from human tissue and RNA from microbes infiltrating the tissue, and analyzes their interrelationships. Through this, researchers can observe human cellular responses to the distribution of specific microbes at a high level of resolution.

Analysis of intestinal tissue from Crohn's disease patients revealed a significant increase in microbial distribution in areas with severe inflammation. It was confirmed that the greater the extent of microbial distribution, the shorter the relapse period and the higher the severity. Yonsei Medical Center

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Using this newly developed pipeline, the team analyzed intestinal tissue from Crohn’s disease patients and confirmed that microbial distribution in Crohn’s-affected tissue was significantly higher than in normal intestinal tissue. In particular, areas with severe inflammation showed a much greater increase in microbial distribution. The extent of this microbial distribution was strongly correlated with the timing of disease recurrence and the severity observed during endoscopic examinations, indicating the potential to predict the prognosis of Crohn’s disease patients based on microbial distribution.

The team also assessed the degree of cell death in human cells according to the presence of microbes. Through this analysis, they identified numerous candidate beneficial bacteria and pathogens related to Crohn’s disease, including some previously unreported bacterial strains that could serve as new therapeutic candidates. Additionally, by identifying RNAs whose expression was either induced or suppressed depending on the type of microbe, they inferred the interactions between microbes and human intestinal cells.

Professor Ko Hong stated, "The microbial profiling technology developed in this study can be applied not only to Crohn’s disease but also to research on various microbe-related diseases. In particular, the identification of beneficial and pathogenic bacteria is expected to contribute to the development of microbe-based therapeutic strategies, prognosis prediction, and the determination of treatment directions for patients."

This study was supported by the Convergence Physician-Scientist Training Program of the Korea Health Industry Development Institute, the Bio-Industry Technology Development Project of the Ministry of Trade, Industry and Energy and the Korea Institute for Advancement of Technology, and the Bio-Medical Technology Development Project of the Ministry of Science and ICT and the National Research Foundation of Korea.

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