New culprit found in gastric cancer

By Alpana Mohta, MD, DNB, FEADV, FIADVL, IFAAD | Fact-checked by Barbara Bekiesz
Published April 19, 2024

Key Takeaways

  • Helicobacter pylori plays a significant role in the diagnosis and progression of gastric cancer, but only 1%–3% of individuals infected with this bacteria develop gastric cancer. 

  • Research shows that Streptococcus anginosus and other pro-inflammatory oral bacteria contribute to chronic stomach inflammation and cancer progression, even in the absence of H. pylori.

  • Gastric cancer prevention strategies should include managing oral microbes through regular oral hygiene, dental care, and maintaining gut health.

Gastric cancer ranks as the fifth most prevalent cancer globally and is a major contributor to increasing cancer-related mortality rates. Traditionally, Helicobacter pylori has been recognized as a significant risk factor for this type of cancer, and it is categorized as a group 1 carcinogen, meaning there is sufficient evidence to suggest that it leads to cancer in humans. 

However, only 1%–3% of those infected with H. pylori actually develop gastric cancer, suggesting that other factors also play a role.[] 

Additionally, up to 20% of patients with chronic gastritis, a common precursor of gastric cancer, don't harbor H. pylori.[] Recent studies suggest a considerable number of non-H. pylori microbes exist in the gastric mucosa.

Oral pathogens and gastric cancer

Oral bacteria like Fusobacterium, Prevotella, Peptostreptococcus, Veillonella, Corynebacterium, and Streptococcus are more abundant in the stomach lining of gastric carcinoma patients. The upregulation of these pro-inflammatory bacteria in saliva has been linked with both the development and progression of gastric cancer.[]

A recent study by the Faculty of Medicine at the Chinese University of Hong Kong has uncovered the role of Streptococcus anginosus in the development of gastric cancer.[]

S. anginosus is a bacterium commonly found in the mouth, throat, intestines, and vagina. It is an opportunistic pathogen that thrives in acidic environments, making it capable of surviving and colonizing the gastric mucosa. 

The research team focused on the gastric microbiome in non-H. pylori infected mice at various stages of gastric tumor development. They found an abundance of S. anginosus in the gastric mucosa of mice with gastric cancer. 

Key findings included:

  • S. anginosus infection for 2 weeks mimicked mild to moderate stomach inflammation observed in H. pylori infection.

  • Prolonged S. anginosus infection (up to 1 year) led to persistent stomach inflammation, matching the chronic effects of H. pylori and starting from 3 months post-infection.

  • This inflammation accelerated malignant cell transformation, fostering a cancer-friendly environment.

  • Co-infection with S. anginosus and H. pylori intensified chronic inflammation after 3 months, doubling the impact of individual infections.

  • S. anginosus caused a sequence of cancer-indicative changes: increased gastric cell growth at 6 months, raised stomach acidity at 9 months, and transformation to pre-cancerous cells in 1 year.

  • The bacterium disrupted stomach microbiota, elevating pro-inflammatory oral microbes and reducing probiotic bacteria like Lactobacillus.

  • S. anginosus infection promoted tumor growth when stomach cancer cells were implanted in mice, at times doubling tumor size and weight.

  • S. anginosus attaches to gastric cells using its TMPC protein, binding to the ANXA2 receptor and activating oncogenic MAPK signaling, thus advancing gastric cancer progression.

This research could pave the way to a new direction in understanding the disease's pathogenesis, especially considering the higher risk when S. anginosus coexists with H. pylori.

Other pathogenic bacteria

The non–H. pylori bacteria can produce harmful metabolites like nitrosated compounds and urease, which are involved in the pathogenesis of gastric cancer. A 2023 review from Frontiers in Microbiology suggests a possible role of multiple micro-organisms.[]

  • Streptococcus salivarius promotes inflammation, speeding up gastric cancer progression. 

  • Propionibacterium acnes triggers lymphocytic gastritis, which can precipitate the malignant transformation of gastric cells.

  • Prevotella copri is preferentially present in gastric cancer patients.

  • Stenotrophomonas and Selenomonas help cancer cells cloak from the immune system. 

  • Fusobacterium nucleatum can create an environment that suppresses the immune response, aiding the proliferation of malignant cells.

Preventative strategies

Owing to the pathogenic role of oral microbiota, which can be swallowed into the stomach and propagate the risk of gastric cancer, advise your patients to maintain good oral hygiene.

For H. pylori infection, aim for eradication therapy. Given increasing antibiotic resistance, quadruple therapy—combining a proton pump inhibitor (PPI), bismuth, metronidazole, and tetracycline, enhanced with lactobacilli—proves more effective than triple therapy.[]

The Chinese researchers observe that the complementary use of probiotics, prebiotics, and dietary fiber alongside H. pylori eradication therapy can regulate the gut microbiota and boost immune responses. A diet rich in fruits and vegetables, with reduced salt and red meat, is also advisable for gastric cancer prevention.

Advise patients against the long-term use of NSAIDs and PPIs. NSAIDs can cause gastric inflammation and mucosal damage, while long-term PPIs encourage the overgrowth of H. pylori and non-H. pylori bacteria in the stomach.[][][]

Recent studies, as discussed in Frontiers in Microbiology, have also explored fecal microbiota transplantation to restore healthy gut microbiota. This approach has shown promise in human studies but still requires validation in cancer clinical trials.

What this means for you

Gastroenterologists can advise heir patients to maintain rigorous oral hygiene to mitigate the risk of gastric carcinoma linked to pro-inflammatory oral microbes. This should include thorough brushing, regular flossing, and using antiseptic mouthwash. Explaining the importance of routine dental check-ups can increase early detection and improve management of any oral health condition.

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