2. Academic Validation
  3. Streptococcus anginosus-derived methionine promotes gastric cancer progression

Streptococcus anginosus-derived methionine promotes gastric cancer progression

  • Gut. 2026 Jun 9;75(7):1279-1296. doi: 10.1136/gutjnl-2025-336966.
Cheng-Bei Zhou # 1,  Li-Cong Zhao # 1,  Youwen Qin # 2 3,  Jingchen Yu # 4,  Wenxi Li # 3,  Qianhui Feng 5 6,  Xin Tong 3,  Resalaiti Abuduaini 1,  Shi-Yuan Lu 1 7,  Huang Tang 8,  Ya-Xuan Zhang 1,  Yun Cui 1,  Liang Xiao 3,  Lin-Hong Song 1,  Le-Kai Ni 1,  Kui Wu 5,  Huanzi Zhong 5,  Yi-Chao Jiang 1,  Yuanqiang Zou 3,  Xiao-Xu Leng 1,  Ming Wang 9,  Wen-Yi Zhao 9,  Chao-Jie Wang 9,  Qiang Liu 10,  Jia-Qi Zhang 11,  Cheng Hu 12,  Ying-Xuan Chen 1,  Yu-Feng Yao 8,  Shida Zhu 5,  Jing-Yuan Fang 13
Affiliations

Affiliations

  • 1 Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • 2 BGI Genomics, Shenzhen, China [email protected] [email protected].
  • 3 State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Shenzhen, China.
  • 4 Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 5 BGI Genomics, Shenzhen, China.
  • 6 School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, China.
  • 7 Department of Gastroenterology, Secondary Affiliated Hospital of Zhejiang University, Hangzhou, China.
  • 8 Laboratory of Bacterial Pathogenesis, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 9 Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
  • 10 Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • 11 Department of Pharmacy, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • 12 Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • 13 Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China [email protected] [email protected].
  • # Contributed equally.
PMID: 41482458 DOI: 10.1136/gutjnl-2025-336966
Abstract

Background: Streptococcus anginosus has been linked with an increasing risk of gastric Cancer (GC) and recognised as a signature for GC screening.

Objective: To investigate the promotional effect of S. anginosus in terms of its metabolic interactions with the host.

Design: We used the functional profiles of shotgun metagenomic Sequencing from stools to detect bioactive molecules relevant to S. anginosus. In vivo and in vitro experiments were used to validate the facilitation of S. anginosus to GC progression. S. anginosus clinical strains were isolated and cultivated from cancerous tissues to verify its promotion of GC via methionine production. S. anginosus ΔmetE mutant strains were constructed to confirm the critical role of metE in methionine biosynthesis.

Results: We verified S. anginosus facilitated GC progression in vivo and in vitro. Our functional analysis of metagenomes revealed a significant enrichment of Bacterial methionine biosynthesis pathways in GC patients with high S. anginosus abundance. Methionine, identified here as one of the primary microbial metabolites derived from S. anginosus, contributed to GC progression in humans and mice. S. anginosus strains from cancerous tissues were found to promote GC via methionine production. We further observed a higher abundance and prevalence of metE gene in Cancer stool metagenomes. By constructing an S. anginosus ΔmetE mutant strain, we confirmed the critical role of metE in methionine biosynthesis.

Conclusion: Our results elucidate the role of S. anginosus-derived methionine in GC progression, shedding light on intricate metabolic interplay between S. anginosus and host.

Keywords

GASTRIC CANCER; METAGENOMICS; MICROBIOME.

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