Huang DB, Chen BS, Wang AP, Hu XZ, Xu YJ. Polymerase chain reaction detection of Streptococcus anginosus in digestive diseases and its immunomodulation in rat gastric cancer model. World J Gastrointest Oncol 2026; 18(8): 119026 [DOI: 10.4251/wjgo.119026]
Corresponding Author of This Article
Ye-Jin Xu, Chief Physician, Department of Infectious Diseases, Jinhua Municipal Central Hospital, No. 365 Renmin East Road, Jinhua 321000, Zhejiang Province, China. xuyejinfox@163.com
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Medicine, General & Internal
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research-article
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Huang DB, Chen BS, Wang AP, Hu XZ, Xu YJ. Polymerase chain reaction detection of Streptococcus anginosus in digestive diseases and its immunomodulation in rat gastric cancer model. World J Gastrointest Oncol 2026; 18(8): 119026 [DOI: 10.4251/wjgo.119026]
Dong-Biao Huang, Xiu-Zhen Hu, Clinical Laboratory, Panan County People’s Hospital, Jinhua 322300, Zhejiang Province, China
Bai-Song Chen, Department of Surgery, Panan County People’s Hospital, Jinhua 322300, Zhejiang Province, China
Ai-Ping Wang, Department of Pediatrics, Panan County People’s Hospital, Jinhua 322300, Zhejiang Province, China
Ye-Jin Xu, Department of Infectious Diseases, Jinhua Municipal Central Hospital, Jinhua 321000, Zhejiang Province, China
Author contributions: Huang DB and Chen BS has been involved in drafting the manuscript, designed the research study; Huang DB, Wang AP, Hu XZ and Xu YJ performed the research; Wang AP and Hu XZ collected and analyzed the data; all authors have been involved in revising manuscript critically for important intellectual content, participated sufficiently in the work to take public responsibility for appropriate portions of the content and agreed to be accountable for all aspects of the work in ensuring that questions related to its accuracy or integrity, give final approval of the version to be published.
AI contribution statement: The answering-reviewers has been accurately translated into English and has been polished using translation software. No data analysis or writing assistance was conducted.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Boards of Panan County People’s Hospital, No. 2024-105.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the of Biomedical Analysis and Testing Center, National University Science Park, Zhejiang University, No. SYXK (Yue)20250398.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: There is no additional data available.
Corresponding author: Ye-Jin Xu, Chief Physician, Department of Infectious Diseases, Jinhua Municipal Central Hospital, No. 365 Renmin East Road, Jinhua 321000, Zhejiang Province, China. xuyejinfox@163.com
Received: February 6, 2026 Revised: March 11, 2026 Accepted: June 22, 2026 Published online: August 15, 2026 Processing time: 177 Days and 8.5 Hours
Abstract
BACKGROUND
Streptococcus anginosus (S. anginosus), a commensal bacterium of the oral cavity, has been associated with digestive infections; however, its role in tumorigenesis remains unclear.
AIM
To characterize S. anginosus colonization in digestive diseases and evaluate its immunomodulatory effects in a rat model of gastric cancer.
METHODS
We prospectively enrolled 93 patients (January-December 2025) undergoing gastroscopy/colonoscopy with pathologically confirmed diagnoses of erosive gastritis (n = 45), digestive polyps (gastric or intestinal; n = 14), peptic ulcers (n = 24), and digestive tract tumors (gastric or colorectal cancer; n = 10). Gastric/colonic mucosal biopsies and gastric fluid or fecal samples were collected. S. anginosus was detected by polymerase chain reaction using species-specific primers, and the positivity rates and relative loads were compared across diseases and sampling sites. Multivariate logistic regression was used to assess the association between S. anginosus positivity and digestive tract tumors. A chemically induced gastric cancer rat model was established, and rats were randomized into control, cancer model, and cancer + S. anginosus intervention groups.
RESULTS
Baseline sex, age, body mass index, and Helicobacter pylori status were comparable among the groups (P > 0.05), although patients with tumors were older (P < 0.05). S. anginosus positivity and relative load were the highest in tumors, intermediate in peptic ulcers and polyps, and the lowest in erosive gastritis (P < 0.05). Patients with tumors had higher mucosal and luminal positivity than those without tumors with higher loads in the tumor-adjacent vs distal mucosa (P < 0.05). Among the 10 patients with tumors, S. anginosus positivity was higher in those with severe mucosal inflammation, TNM III-IV, and nodal metastasis, and the bacterial load was positively correlated with inflammation scores and tumor invasion depth (P < 0.05). In rats, tumor nodule count, maximal diameter, and total tumor volume/weight were greater in the cancer model than in the controls and further increased with S. anginosus intervention (all P < 0.05). Serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels increased in cancer rats vs controls and further increased with S. anginosus (P < 0.05). CD4+ cell, CD8+ T-cell, and CD68+ macrophage infiltration scores were higher in the cancer group than in the control group and further increased in the S. anginosus-infected group (P < 0.05). Bacterial load correlated positively with IL-6, TNF-α, and immune infiltration scores (P < 0.05).
CONCLUSION
S. anginosus colonization is markedly evident in digestive tract tumors and is associated with inflammatory and clinicopathological features. In the rat model of gastric cancer, the increased levels of IL-6 and TNF-α and infiltration of immune cells (including CD8+ T cells) are consistent with the aggravation of tumor burden; however, the increased CD8+ T-cell infiltration does not necessarily indicate effective antitumor immunity, and their functional status and potential mechanisms related to arginine-ornithine metabolism still need further verification. S. anginosus may be an important microecological and immunomodulatory target in the development and progression of digestive tract tumors and warrants further in-depth research.
Core Tip: This study characterizes Streptococcus anginosus (S. anginosus) colonization across digestive diseases and its immunomodulatory role in gastric cancer. In a prospective cohort of 93 patients, S. anginosus positivity and relative load were highest in malignant tumors. Using a chemically induced gastric cancer rat model, S. anginosus colonization was shown to promote tumor progression, elevate serum interleukin-6 and tumor necrosis factor-α levels, and enhance infiltration of CD4+, CD8+ T cells, and CD68+ macrophages. The findings indicate that S. anginosus remodels the tumor immune microenvironment to favor carcinogenesis, suggesting its potential as a microbial and immunotherapeutic target.
