Akkermansia muciniphila improves gastric cancer treatment by modulating the immune microenvironment

Abstract

Background: Gut microbiota is pivotal in tumor occurrence and development, and there is a close relationship between Akkermansia muciniphila (AKK) and cancer immunotherapy. Methods: The effects of AKK and its outer membrane proteins on gastric cancer (GC) were evaluated in vitro and in vivo using cell counting kit-8 assay, flow cytometry, western blotting, ELISA, immunohistochemistry and immunofluorescence. Results: AKK outer membrane protein facilitated apoptosis of GC cells and exerted an immunostimulatory effect (by promoting M1 polarization of macrophages, enhancing expression of cytotoxic T-lymphocyte-related cytokines and suppressing that of Treg-related cytokines). Additionally, AKK and its formulation could inhibit tumor growth of GC and enhance the infiltration of immune cells in tumor tissues. Conclusion: AKK could improve GC treatment by modulating the immune microenvironment.

Plain language summary

Akkermansia muciniphila (AKK) is a type of bacteria found in the human gut that is good for the immune system. We wanted to investigate the effect of AKK on cancer. We extracted a protein from AKK called Amuc. AKK and Amuc inhibited the growth of stomach cancer by encouraging the action of immune cells. AKK may therefore be able to treat stomach cancer.

Summary points

• The Akkermansia muciniphila (AKK) outer membrane protein Amuc promoted apoptosis in gastric cancer cells.

• Amuc increased the number of M1 macrophages and inhibited the number of M2 macrophages.

• Amuc promoted the expression of macrophage proinflammatory factors IL-23 and TNF-α and inhibited the expression of TGF-β.

• Amuc promoted macrophage polarization toward M1 and inhibited polarization toward M2.

• Amuc promoted the expression of cytotoxic T-lymphocyte-associated cytokines IFN-γ and TNF-α, and inhibited the expression of Treg-associated cytokine IL-10.

• AKK and its preparations significantly inhibited tumor growth.

• AKK was able to promote CD8⁺ T immune infiltration and TNF-α secretion.

• AKK is expected to be an adjuvant regulatory target for gastric cancer immunotherapy.

Keywords: :

• Akkermansia muciniphila
• gastric cancer
• immune microenvironment
• macrophages

Financial disclosure

This work was supported by the Social Development Project Fund of Jinhua Science and Technology Bureau in Zhejiang Province (2022-3-148). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This work was approved by the Experimental Animal Welfare and Ethics Committee of Jinhua Municipal Central Hospital (AL-JHYY202202).

Additional information

Funding

This work was supported by the Social Development Project Fund of Jinhua Science and Technology Bureau in Zhejiang Province (2022-3-148).