Inflammation as a Mediator of Microbiome Dysbiosis-Associated DNA Methylation Changes in Gastric Premalignant Lesions

Lingjun Yan; Wanxin Li; Fenglin Chen; Junzhuo Wang; Jianshun Chen; Ying Chen; Weimin Ye

doi:10.1007/s43657-023-00118-w

Inflammation as a Mediator of Microbiome Dysbiosis-Associated DNA Methylation Changes in Gastric Premalignant Lesions

Phenomics. 2023 Sep 6;3(5):496-501. doi: 10.1007/s43657-023-00118-w. eCollection 2023 Oct.

Authors

Lingjun Yan^#^{1

2}, Wanxin Li^#^{1

2}, Fenglin Chen³, Junzhuo Wang^{1

2}, Jianshun Chen⁴, Ying Chen⁵, Weimin Ye^{1

2

6}

Affiliations

¹ Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, 350122 China.
² Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122 China.
³ Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, 350001 China.
⁴ Changle Center for Disease Prevention and Control, Fuzhou, 350200 China.
⁵ Changle Institute for Cancer Research, Fuzhou, 350200 China.
⁶ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, 17177 Sweden.

^# Contributed equally.

PMID: 37881317
PMCID: PMC10593640 (available on 2024-10-01)
DOI: 10.1007/s43657-023-00118-w

Abstract

Evidence for the influence of chronic inflammation induced by microbial dysbiosis on aberrant DNA methylation supports a plausible connexion between disordered microbiota and precancerous lesions of gastric cancer (PLGC). Here, a comprehensive study including multi-omics data was performed to estimate the relationships amongst the gastric microbiome, inflammatory proteins and DNA methylation alterations and their roles in PLGC development. The results demonstrated that gastric dysbacteriosis increased the risk of PLGC and DNA methylation alterations in related tumour suppressor genes. Seven inflammatory biomarkers were identified for antrum and corpus tissues, respectively, amongst which the expression levels of several biomarkers were significantly correlated with the microbial dysbiosis index (MDI) and methylation status of specific tumour suppressor genes. Notably, mediation analysis revealed that microbial dysbiosis partially contributed to DNA methylation changes in the stomach via the inflammatory cytokines C-C motif chemokine 20 (CCL20) and tumour necrosis factor receptor superfamily member 9 (TNFRSF9). Overall, these results may provide new insights into the mechanisms that might link the gastric microbiome to PLGC.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-023-00118-w.

Keywords: DNA methylation; Gastric premalignant lesions; Inflammation; Mediation analysis; Microbiome dysbiosis.