A groundbreaking study co-led by researchers at Nanyang Technological University (NTU) Singapore has uncovered how Streptococcus anginosus, a bacterium commonly residing in the human mouth, throat, intestines, and vagina, contributes to the development of stomach cancer, also known as gastric cancer. This discovery challenges the long-held focus on Helicobacter pylori as the primary bacterial culprit and opens new avenues for prevention and treatment in Singapore, where gastric cancer claims around 300 to 500 lives annually, ranking among the top 10 cancer-related deaths.

Typically causing mild infections like sore throats or skin abscesses in healthy individuals, S. anginosus was found enriched in gastric cancer tissues across a massive dataset. The research, published in prestigious journals like Cell and Gut, highlights NTU's pivotal role in advancing global understanding of microbial influences on oncology, positioning the university as a leader in Singapore's biomedical research landscape.

🦠 The Role of Streptococcus anginosus in Gastric Pathogenesis

Streptococcus anginosus Group (SAG) bacteria, including S. anginosus, are part of the normal human microbiome. However, under certain conditions, they can translocate to the stomach, triggering chronic inflammation that precedes metaplasia, dysplasia, and ultimately carcinoma. NTU researchers, led by Professor Joseph Sung, NTU's Senior Vice President for Health and Life Sciences and Dean of the Lee Kong Chian School of Medicine (LKCMedicine), analyzed metagenomic data from over 47,000 gastric biopsies and resections worldwide. They discovered S. anginosus in 20.7% of gastric cancers compared to just 5.9% in non-malignant tissues—a statistically significant enrichment.

This translocation likely occurs via oral-gastric axis migration, exacerbated by poor oral hygiene or acid reflux. Once in the stomach lining, S. anginosus adheres via surface proteins, damaging epithelial cells and promoting a pro-tumorigenic microenvironment rich in inflammatory cytokines like IL-6 and TNF-α.

NTU's Innovative Methodology: From Big Data to Mouse Models

The NTU-led team's approach was multi-pronged. First, they leveraged computational metagenomics on public datasets, identifying SAG as a consistent biomarker. Bioinformatics tools filtered noise from sequencing artifacts, confirming viability through PCR and culture-independent methods.

In vivo validation used gnotobiotic mice colonized with S. anginosus alongside a chemical carcinogen (MNU). Step-by-step: 1) Mice developed gastritis within weeks; 2) Bacterial load correlated with atrophy scores; 3) Tumors doubled in size/weight vs controls; 4) Knocking out bacterial adhesin Pil1 reduced colonization and oncogenesis by 70%.

Key Findings: Enrichment and Tumor Promotion Confirmed

The study quantified S. anginosus DNA 3.5-fold higher in cancers. Metabolomic analysis revealed methionine production by the bacteria fueling cancer cell proliferation via mTOR pathway activation. In Singapore cohorts, prevalence mirrored global trends, with higher rates in H. pylori-negative cases—suggesting SAG as a 'second hit'.

Professor Sung noted, 'This lays groundwork for human trials targeting bacterial adhesion, potentially reducing gastric cancer incidence beyond H. pylori eradication.'

Gastric Cancer Burden in Singapore: Why This Matters Locally

Singapore faces a rising gastric cancer incidence, projected at 8.0 per 100,000 for men and 16.1 for women by 2026, per global estimates. Over 60% diagnosed late (stages III-IV), with 5-year survival <20%. NTU's work aligns with national efforts like the Singapore Gastric Cancer Consortium (SGCC), involving NTU LKCMedicine, NUS Medicine, Duke-NUS, and A*STAR.

Cultural factors like high salted fish/smoked meat consumption amplify risks, but microbial insights enable precision screening via gastric juice biopsies.

Complementary Insights from Duke-NUS 2026 Study

Building on NTU's findings, a January 2026 Duke-NUS/SGCC study analyzed 1,500+ intestinal metaplasia (IM) samples across Asia. ARID1A mutations (17-27% cases), clonal hematopoiesis (age >60), SBS17 smoking signature, and oral Streptococcus leakage raised risk 6-fold. Pyrvinium pamoate reversed IM in organoids/mice, priming clinical trials.

Co-authored by NTU affiliates, it underscores Singapore's collaborative ecosystem.

Singapore's Research Powerhouse: NTU LKCMedicine Leading the Charge

NTU's Lee Kong Chian School of Medicine pioneers translational research, with Prof Sung's team exemplifying Asia-Pacific leadership. Facilities like the NTU Institute for Health Technologies support microbiome-oncology integration. SGCC's $25M NMRC grant fuels multi-omics gastric studies.

Stakeholder Perspectives: Clinicians, Patients, and Policymakers

Singapore oncologists hail the findings for non-H. pylori cases (30-40% local incidence). Patient advocates push for subsidized endoscopy. MOH eyes microbiome screening in national programs. NTU's Prof Sung emphasizes, 'Early bacterial detection could save lives.'

Challenges and Solutions: From Bench to Bedside

• Challenge: Contamination in biopsies. Solution: Viability assays.
• Challenge: Antibiotic resistance. Solution: Adhesin-targeted therapies.
• Challenge: Late diagnosis. Solution: Liquid biopsy for SAG DNA.

Future Outlook: Prevention Strategies and Clinical Trials

NTU plans Phase I trials for Pil1 inhibitors. Probiotics/oral hygiene campaigns could cut translocation. Integrated with H. pylori vaccines, incidence may drop 50% by 2040. Singapore's aging population (1 in 4 cancer lifetime risk) demands urgency.

Photo by Gokul on Unsplash

Opportunities in Singapore's Biomedical Research Landscape

NTU LKCMedicine offers PhD/postdoc roles in microbiome-oncology. Singapore's RIE2025 invests S$25B in health tech, creating jobs in genomics, AI diagnostics. Aspiring researchers can leverage NTU's global partnerships for impactful careers.