Bifidobacterium Adolescentis Induces Decorin Macrophages Via TLR2 to Suppress Colorectal Carcinogenesis

Overview

Journal J Exp Clin Cancer Res

Publisher Biomed Central

Specialty Oncology

Date 2023 Jul 18

PMID 37464382

Authors

Yifeng Lin

Lina Fan

Yadong Qi

Chaochao Xu

Dingjiacheng Jia

Yao Jiang

Shujie Chen

Liangjing Wang

Affiliations

Soon will be listed here.

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.

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