From microbial dysbiosis to putative epigenetic locking: a hypothesis-driven framework for the pathogenesis and future therapeutic perspectives of gastric intestinal metaplasia.
4 affiliations
- 1Affiliated Hospital of Jiangnan University, Wuxi City, Jiangsu Province, 214122, China.
- 2Jiangnan University, 1000 Hefeng Road, Binhu District, Wuxi City, Jiangsu Province, 214122, China.
- 3Affiliated Hospital of Jiangnan University, Wuxi City, Jiangsu Province, 214122, China. [email protected].
- 4Jiangnan University, 1000 Hefeng Road, Binhu District, Wuxi City, Jiangsu Province, 214122, China. [email protected].
Abstract
Background
Intestinal metaplasia (IM) is a key precancerous lesion connecting chronic atrophic gastritis and gastric cancer in the Correa cascade, and its risk of progression has significant individual heterogeneity. A potential explanatory framework for this heterogeneity involves interactions between gastric microbiota imbalance and host epigenetic remodeling. Current research needs to clarify the relationship between microbial community stratification and IM reversibility, particularly whether high-risk microbial signatures and putative epigenetic "silencer locking" states are associated with IM regression or persistence.Method
This hypothesis-driven narrative review synthesizes representative findings from metagenomic, metabolomic, transcriptomic, and epigenomic studies to develop a conceptual framework for how interactions between Helicobacter pylori (H. pylori), non-H. pylori microorganisms, and host mucosal responses may be associated with the initiation and progression of IM, potentially through microbiota-associated, host-derived, and mixed-origin metabolic signals that converge on epigenetic and transcriptional regulation.Result
Available evidence suggests that microbial networks in IM may include potential pro-inflammatory interactions between H. pylori and taxa such as Fusobacterium nucleatum (F. nucleatum), as well as possible protective associations involving beneficial bacteria such as Lactobacillus. Based on this, we propose a three-stage working model, H. pylori initiation, putative microbial network amplification, and silencer remodeling-associated progression, and discuss a candidate intervention framework involving probiotics, miR-185, and Wnt/β-catenin signaling, which should be regarded as a testable hypothesis rather than a clinically validated reversal strategy.Conclusion
These findings may provide candidate mechanistic targets and a theoretical basis for future risk stratification, dynamic monitoring, and individualized intervention of IM, pending validation in prospective clinical studies.
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BibTeX
@article{sheng2026from,
title = {{From microbial dysbiosis to putative epigenetic locking: a hypothesis-driven framework for the pathogenesis and future therapeutic perspectives of gastric intestinal metaplasia.}},
author = {Yingyue Sheng and Chaosheng Yan and Yuzhe Yin and Zhipeng Zeng and Xinyu Pei and Chenyu Ma and Jingjing Rao and Haowen Sun and Yuzheng Xue},
journal = {Journal of translational medicine},
year = {2026},
month = jul,
doi = {10.1186/s12967-026-08730-w},
url = {https://europepmc.org/article/MED/42958549},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - From microbial dysbiosis to putative epigenetic locking: a hypothesis-driven framework for the pathogenesis and future therapeutic perspectives of gastric intestinal metaplasia.
AU - Yingyue Sheng
AU - Chaosheng Yan
AU - Yuzhe Yin
AU - Zhipeng Zeng
AU - Xinyu Pei
AU - Chenyu Ma
AU - Jingjing Rao
AU - Haowen Sun
AU - Yuzheng Xue
PY - 2026
DA - 2026/07/31
JO - Journal of translational medicine
DO - 10.1186/s12967-026-08730-w
UR - https://europepmc.org/article/MED/42958549
AB - Background Intestinal metaplasia (IM) is a key precancerous lesion connecting chronic atrophic gastritis and gastric cancer in the Correa cascade, and its risk of progression has significant individual heterogeneity. A potential explanatory framework for this heterogeneity involves interactions between gastric microbiota imbalance and host epigenetic remodeling. Current research needs to clarify the relationship between microbial community stratification and IM reversibility, particularly whether high-risk microbial signatures and putative epigenetic "silencer locking" states are associated with IM regression or persistence.Method This hypothesis-driven narrative review synthesizes representative findings from metagenomic, metabolomic, transcriptomic, and epigenomic studies to develop a conceptual framework for how interactions between Helicobacter pylori (H. pylori), non-H. pylori microorganisms, and host mucosal responses may be associated with the initiation and progression of IM, potentially through microbiota-associated, host-derived, and mixed-origin metabolic signals that converge on epigenetic and transcriptional regulation.Result Available evidence suggests that microbial networks in IM may include potential pro-inflammatory interactions between H. pylori and taxa such as Fusobacterium nucleatum (F. nucleatum), as well as possible protective associations involving beneficial bacteria such as Lactobacillus. Based on this, we propose a three-stage working model, H. pylori initiation, putative microbial network amplification, and silencer remodeling-associated progression, and discuss a candidate intervention framework involving probiotics, miR-185, and Wnt/β-catenin signaling, which should be regarded as a testable hypothesis rather than a clinically validated reversal strategy.Conclusion These findings may provide candidate mechanistic targets and a theoretical basis for future risk stratification, dynamic monitoring, and individualized intervention of IM, pending validation in prospective clinical studies.
SN - 1479-5876
ER -