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| Researchers took biopsies of AIG patients with and without neuroendocrine tumor growth to understand their bacterial communities Image Credit: Osaka Metropolitan University |
Researchers from Osaka Metropolitan University have discovered how the balance of bacteria in the stomach affects the growth of neuroendocrine tumors (NETs). By identifying the specific bacteria involved and the biochemical reactions that cause tumor growth, the researchers hope to create a new diagnostic technique to detect which patients are most likely to develop cancer.
Autoimmune gastritis (AIG) is a long-term condition in which the body’s immune system mistakenly attacks the lining of the stomach. This ongoing immune response gradually damages the stomach, affecting how it functions and its ability to protect itself from harmful agents. Over time, these changes can increase the risk of developing NETs, a type of tumor that develops from hormone-producing cells in the stomach.
The stomach is home to the gastric microbiota, a diverse community of microorganisms that are important for maintaining health. The research group led by Dr. Koji Otani of the Osaka Metropolitan University Graduate School of Medicine analyzed changes in the gastric microbiota and tissue-derived metabolites using DNA extracted from biopsy specimens to understand how these microorganisms are affected in AIG patients. Understanding how this process occurs might help to understand how tumors form in the stomach.
In patients, “α-diversity” is often used to assess gut health, as it reflects the number of different microbial species present in a given sample. High α-diversity is usually a sign of a healthy, well-balanced gut; however, it was found to be reduced in AIG patients.
Intriguingly, distinct bacterial communities were observed depending on whether the patient had developed an NET or not. This was supported by heatmap analysis of the relative abundance of gastric microbiota that revealed distinct compositional patterns in the group that had developed NETs.
In particular, the NET-positive group showed increased levels of Haemophilus parainfluenzae and Fusobacterium species, particularly F. periodonticum and F. nucleatum. While these bacteria are typically found in healthy stomachs, increased levels are often responsible for inflammatory conditions.
In addition, they found decreases in lactic acid bacteria and Streptococcus salivarius that are involved in maintaining health and commonly inhibit harmful bacteria.
The group used metabolomic analysis to investigate the biochemical reactions that were occurring. They found that the cells of AIG patients were changing the way they generate and use energy, a process known as metabolic reprogramming, compared to normal tissue.
This metabolic reprogramming was characterized by decreased activity in the glycolysis and TCA cycle pathways, cycles commonly used to generate energy. Instead, metabolism had shifted towards alternative pathways to meet energy demands. This shift in metabolism can affect cell function, as well as inflammation and tissue remodeling processes.
The researchers concluded that specific tissue metabolic patterns were associated with AIG, and specific gastric microbiota signatures were associated with development of gastric NETs. “The study suggests that in AIG patients, changes in host metabolism occur before alterations in the gastric microbiota, potentially creating a microenvironment that favors the growth of bacteria linked to gastric NET formation,” Dr. Otani explained. “Our findings are expected to enhance understanding of the progression from AIG onset to gastric NET development and support the creation of new diagnostic markers for early detection and prevention.”
Research information: Neuroendocrine Tumors
Research Material: Gut brain connection
Funding: This work was partially supported by JSPS KAKENHI Grant-in-Aid for Scientific Research (C) (Grant Number JP22K08040).
Published in journal: Journal of Gastroenterology
Authors: Koji Otani, Geicho Nakatsu, Kosuke Fujimoto, Daichi Miyaoka, Noriaki Sato, Yuji Nadatani, Yu Nishida, Hirotsugu Maruyama, Masaki Ominami, Shusei Fukunaga, Shuhei Hosomi, Fumio Tanaka, Seiya Imoto, Satoshi Uematsu, Toshio Watanabe, and Yasuhiro Fujiwara
Source/Credit: Osaka Metropolitan University
Reference Number: mcb100825_01
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