Role of Streptococcus anginosus in gastric cancer
Less well known than Helicobacter pylori, Streptococcus anginosus may play a role in gastric cancer through its production of methionine.
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Numerous studies have implicated Helicobacter pylori in gastric cancer. In recent years, other bacteria in the gut microbiota shave also come under scrutiny, such as Streptococcus anginosus, which is thought to promote gastric carcinogenesis in mice and may serve as a screening biomarker.
To find out more, a research team 1 carried out both in vitro and in vivo studies on the cancer-promoting effect of S. anginosus through its metabolic interactions with the host.
Top 5 The incidence rate and mortality of gastric cancer rank among the top five malignancies worldwide. ¹
Top 3 Gastric cancer was one of the top three causes of cancer-related deaths in China over 2005–2020. ¹
4th and 5th Gastric cancer is the 4th leading cause of cancer-related deaths among men and the 5th among women. ²
Role of S. anginosus in gastric tumors
A metagenomic analysis conducted on a large clinical cohort of 106 gastric cancer patients and 106 controls with chronic gastritis revealed an enrichment of S. anginosus (and, to a lesser extent, S. constellatus) and methionine in the gastrointestinal tract mucosa and feces of the gastric cancer patients.
Additional in vitro and in vivo experiments highlighted that S. anginosus facilitates the development of gastric tumors via methionine, one of its main metabolic byproducts.
68%
The Asian continent is the major contributor to the expected burden, with more than 10.6 million cases (68% of all cases), followed by the Americas (2.0 million; 13%), Africa (1.7 million; 11%), Europe (1.2 million; 8%) and Oceania (0.07 million; 0.4%). ³
The bacterium thus appears to play a role in the disruptions of methionine metabolism involved in the development of gastric cancer, providing non-dietary sources of essential amino acids required by cancer cells.
968 784 There were 968,784 new cases of stomach cancer in 2022. ⁴
9.2 per 100,000 The global incidence of stomach cancer was 9.2 cases per 100,000 people in 2022, but reached 27.0 per 100,000 in South Korea, 27.6 per 100,000 in Japan, and 35.5 per 100,000 in Mongolia. ⁴
660 175 660 175 personnes sont décédées d’un cancer de l’estomac en 2022. ⁴
Key role of the metE gene
Clinical strains of S. anginosus were isolated and cultured from tumor tissues to verify their ability to promote gastric cancer through methionine production. This also lays the foundation for future work on the subtyping of S. anginosus subspecies.
The authors identified the metE gene as a key player in methionine biosynthesis from S. anginosus. This gene was more abundant in patients with gastric cancer and was strongly associated with the presence of the bacterium.
By creating a ΔmetE mutant strain in which the metE gene was inactivated, they showed that inactivating this gene:
- reduced methionine production,
- slowed the proliferation of cancer cells,
- and limited tumor formation in mice.
This confirms the central role of metE in the carcinogenic effect of S. anginosus.
6,1 The overall mortality rate from stomach cancer worldwide was 6.1 per 100,000 people in 2022, but reached 15.4 per 100,000 in Iran, 10.9 per 100,000 in Vietnam, and 9.4 per 100,000 in China. ⁴
15,6 Assuming no change in future incidence rates, a lifetime estimate of 15.6 million new gastric cancer cases is expected among all men and women born between 2008 and 2017 globally. ³
50 Gastric cancer incidence rates at younger ages (<50 years) are increasing in both low- and high-incidence populations. ³
Future therapeutic target?
A better understanding of the mechanisms by which the pathogenic bacterium S. anginosus promotes gastric cancer could contribute to the identification of new therapeutic or preventive targets. Could inhibiting S. anginosus colonization or growth reduce methionine production and thus slow the growth of gastric tumors?
Could it also improve the effectiveness of immunotherapy or chemotherapy in patients with gastric cancer ?
These findings open up many avenues for future research.
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