2. Academic Validation
  3. Bifidobacterium adolescentis induces Decorin+ macrophages via TLR2 to suppress colorectal carcinogenesis

Bifidobacterium adolescentis induces Decorin+ macrophages via TLR2 to suppress colorectal carcinogenesis

  • J Exp Clin Cancer Res. 2023 Jul 18;42(1):172. doi: 10.1186/s13046-023-02746-6.
Yifeng Lin # 1 2,  Lina Fan # 1 2,  Yadong Qi # 2 3,  Chaochao Xu 1 2,  Dingjiacheng Jia 1 2,  Yao Jiang 1 2,  Shujie Chen 4 5 6 7,  Liangjing Wang 8 9 10 11
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310009, China.
  • 2 Institute of Gastroenterology, Zhejiang University, Hangzhou, China.
  • 3 Department of Gastroenterology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang Province, 310003, China.
  • 4 Institute of Gastroenterology, Zhejiang University, Hangzhou, China. chenshujie77@zju.edu.cn.
  • 5 Department of Gastroenterology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang Province, 310003, China. chenshujie77@zju.edu.cn.
  • 6 Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China. chenshujie77@zju.edu.cn.
  • 7 Research Center of Prevention and Treatment of Senescent Disease, School of Medicine, Zhejiang University, Hangzhou, China. chenshujie77@zju.edu.cn.
  • 8 Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310009, China. wangljzju@zju.edu.cn.
  • 9 Institute of Gastroenterology, Zhejiang University, Hangzhou, China. wangljzju@zju.edu.cn.
  • 10 Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China. wangljzju@zju.edu.cn.
  • 11 Research Center of Prevention and Treatment of Senescent Disease, School of Medicine, Zhejiang University, Hangzhou, China. wangljzju@zju.edu.cn.
  • # Contributed equally.
PMID: 37464382 DOI: 10.1186/s13046-023-02746-6
Abstract

Background: The interplay between gut microbiota and tumor microenvironment (TME) in the pathogenesis of colorectal Cancer (CRC) is largely unknown. Here, we elucidated the functional role of B. adolescentis and its possible mechanism on the manipulation of Decorin+ macrophages in colorectal Cancer.

Methods: The relative abundance of B. adolescentis in tumor or para-tumor tissue of CRC patients was analyzed. The role of B. adolescentis was explored in the CRC animal models. The single cell-RNA Sequencing (scRNA-seq) was used to investigate the myeloid cells subsets in TME. The expression level of TLR2/YAP axis and its downstream Decorin in macrophages were tested by Western blot and qRT-PCR. Knockdown of Decorin in Raw264.7 was performed to investigate the effect of Decorin+ macrophages on subcutaneous tumor formation. Multi-immunofluorescence assay examined the number of Decorin+ macrophages on the CRC tissue.

Results: We found that the abundance of B. adolescentis was significantly reduced in tumor tissue of CRC patients. Supplementation with B. adolescentis suppressed AOM/DSS-induced tumorigenesis in mice. ScRNA-seq and animal experiment revealed that B. adolescentis increased Decorin+ macrophages. Mechanically, Decorin was activated by TLR2/YAP axis in macrophages. The abundance of B. adolescentis was correlated with the number of Decorin+ macrophages and the expression level of TLR2 in tumor tissue of CRC patients.

Conclusions: These results highlight that B. adolescentis induced Decorin+ macrophages and provide a novel therapeutic target for probiotic-based modulation of immune microenvironment in CRC.

Keywords

B.adolescentis; Colorectal cancer; Decorin; Macrophages; TLR2.

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