Small intestine/upper GI Bacteria commonly found in the body contribute to stomach cancer. Streptococcus anginosus promotes gastric inflammation, atrophy, and tumorigenesis in mice (Jan 2024)

[Michael Harrop]

https://medicalxpress.com/news/2024-03-bacteria-commonly-body-contribute-stomach.html
https://www.cell.com/cell/fulltext/S0092-8674(24)00006-0

H. pylori bacteria are classified as carcinogenic (cancer-causing) to humans. But among people infected with the bacteria, only 1 to 3% develop stomach cancer, which suggests that other factors are involved in its development.

Streptococcus anginosus bacteria exist alongside other germs in the mouth, throat, intestines and vagina. Occasionally, they may cause mild infections like sore throats and skin infections. For patients with underlying health conditions or compromised immune systems, the bacteria can lead to more serious infections, such as those that damage the heart and brain.

Since S. anginosus is commonly found in the mouth, the bacterium could be swallowed through saliva and find its way into the stomach. So, one potential way to guard against stomach cancer from developing could be to practice good oral hygiene, said Prof Sung.

Highlights​

• S. anginosus is enriched in the gastric mucosa of patients with GC
• S. anginosus induces gastritis-atrophy-metaplasia-dysplasia sequence in mice
• S. anginosus promotes gastric tumorigenesis
• TMPC-Annexin A2 axis mediates S. anginosus colonization and activates MAPK signaling

Summary​

Streptococcus anginosus (S. anginosus) was enriched in the gastric mucosa of patients with gastric cancer (GC). Here, we show that S. anginosus colonized the mouse stomach and induced acute gastritis. S. anginosus infection spontaneously induced progressive chronic gastritis, parietal cell atrophy, mucinous metaplasia, and dysplasia in conventional mice, and the findings were confirmed in germ-free mice.

In addition, S. anginosus accelerated GC progression in carcinogen-induced gastric tumorigenesis and YTN16 GC cell allografts. Consistently, S. anginosus disrupted gastric barrier function, promoted cell proliferation, and inhibited apoptosis. Mechanistically, we identified an S. anginosus surface protein, TMPC, that interacts with Annexin A2 (ANXA2) receptor on gastric epithelial cells. Interaction of TMPC with ANXA2 mediated attachment and colonization of S. anginosus and induced mitogen-activated protein kinase (MAPK) activation. ANXA2 knockout abrogated the induction of MAPK by S. anginosus.

Thus, this study reveals S. anginosus as a pathogen that promotes gastric tumorigenesis via direct interactions with gastric epithelial cells in the TMPC-ANXA2-MAPK axis.