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other·preclinical research, oncology, gastroenterology, immunology, nutrition·PMC10648432

Lactobacillus plantarum Zhang-LL Inhibits Colitis-Related Tumorigenesis by Regulating Arachidonic Acid Metabolism and CD22-Mediated B-Cell Receptor Regulation

Nutrients · 11 authors, 3 centres

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Mice treated with Zhang-LL, both as live bacteria and a heat-killed preparation, showed significantly inhibited tumorigenesis, reduced colon shortening, and alleviated inflammatory symptoms compared to untreated model controls. Mechanistically, Zhang-LL intervention altered the gut microbiota composition, increasing beneficial bacteria and decreasing pathogenic ones. Furthermore, transcriptomic analysis revealed upregulation of genes related to the CD22-mediated B-cell receptor regulation pathway.

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ORIGINAL PAPER

PMC10648432

Lactobacillus plantarum Zhang-LL Inhibits Colitis-Related Tumorigenesis by Regulating Arachidonic Acid Metabolism and CD22-Mediated B-Cell Receptor Regulation

Nutrients

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ABSTRACT

Abstract Colorectal cancer (CRC) is a significant health concern and is the third most commonly diagnosed and second deadliest cancer worldwide. CRC has been steadily increasing in developing countries owing to factors such as aging and epidemics. Despite extensive research, the exact pathogenesis of CRC remains unclear, and its causes are complex and variable. Numerous in vitro, animal, and clinical trials have demonstrated the efficacy of probiotics such as Lactobacillus plantarum in reversing the adverse outcomes of CRC. These findings suggest that probiotics play vital roles in the prevention, adjuvant treatment, and prognosis of CRC. In this study, we constructed a mouse model of CRC using an intraperitoneal injection of azomethane combined with dextran sodium sulfate, while administering 5-fluorouracil as well as high- and low-doses of L. plantarum Zhang-LL live or heat-killed strains. Weight changes and disease activity indices were recorded during feeding, and the number of polyps and colon length were measured after euthanasia. HE staining was used to observe the histopathological changes in the colons of mice, and ELISA was used to detect the expression levels of IL-1β, TNF-α, and IFN-γ in serum. To investigate the specific mechanisms involved in alleviating CRC progression, gut microbial alterations were investigated using 16S rRNA amplicon sequencing and non-targeted metabolomics, and changes in genes related to CRC were assessed using eukaryotic transcriptomics. The results showed that both viable and heat-killed strains of L. plantarum Zhang-LL in high doses significantly inhibited tumorigenesis, colon shortening, adverse inflammatory reactions, intestinal tissue damage, and pro-inflammatory factor expression upregulation. Specifically, in the gut microbiota, the abundance of the dominant flora Acutalibacter muris and Lactobacillus johnsonii was regulated, PGE2 expression was significantly reduced, the arachidonic acid metabolism pathway was inhibited, and CD22-mediated B-cell receptor regulation-related gene expression was upregulated. This study showed that L. plantarum Zhang-LL live or heat-inactivated strains alleviated CRC progression by reducing the abundance of potentially pathogenic bacteria, increasing the abundance of beneficial commensal bacteria, mediating the arachidonic acid metabolism pathway, and improving host immunogenicity. Keywords: colorectal cancer, Lactobacillus plantarum Zhang-LL, gut microbiota, arachidonic acid metabolism, CD22

CITATION EXPORT

Jingxin Zhu, Wenbo Liu, Zheng Bian et al.. Lactobacillus plantarum Zhang-LL Inhibits Colitis-Related Tumorigenesis by Regulating Arachidonic Acid Metabolism and CD22-Mediated B-Cell Receptor Regulation. Nutrients. (2023). https://doi.org/10.3390/nu15214512

AUTHORS

11 · 3 CENTRES

Jingxin Zhu, Wenbo Liu, Zheng Bian, Yumeng Ma, Zixin Kang, Junhua Jin, Xiangyang Li, Shaoyang Ge, Yanling Hao, Hongxing Zhang, Yuanhong Xie

1Beijing Laboratory of Food Quality and Safety, Beijing Key Laboratory of Agricultural Product Detection and Control of Spoilage Organisms and Pesticide Residue, College of Food Science and Engineering, Beijing University of Agriculture, Beijing 102206, China; [email protected] (J.Z.); [email protected] (W.L.); [email protected] (Z.B.); [email protected] (Y.M.); [email protected] (Z.K.); [email protected] (J.J.); [email protected] (X.L.)
2Beijing HEYIYUAN BIOTECHNOLOGY Co., Ltd., Beijing 100088, China; [email protected]
3Key Laboratory of Functional Dairy, Department of Nutrition and Health, Co-Constructed by Ministry of Education and Beijing Government, China Agricultural University, Beijing 100190, China; [email protected]