Beijing 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.
Beijing HEYIYUAN BIOTECHNOLOGY Co., Ltd., Beijing 100088, China.
Nutrients. 2023 Oct 25;15(21):4512. doi: 10.3390/nu15214512.
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 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 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 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 and 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 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.
结直肠癌（CRC）是一个重大的健康问题，是全球第三大常见的癌症，也是第二大最致命的癌症。由于老龄化和流行等因素，发展中国家的 CRC 发病率一直在稳步上升。尽管进行了广泛的研究，但 CRC 的确切发病机制仍不清楚，其病因复杂且多变。大量的体外、动物和临床试验已经证明了益生菌如 Zhang-LL 可以逆转 CRC 的不良结局。这些发现表明益生菌在 CRC 的预防、辅助治疗和预后中发挥着重要作用。在这项研究中，我们使用腹腔注射偶氮甲烷结合葡聚糖硫酸钠构建了 CRC 小鼠模型，同时给予 5-氟尿嘧啶以及高剂量和低剂量的活菌或热处理的 Zhang-LL 株。在喂养期间记录体重变化和疾病活动指数，安乐死后测量息肉数量和结肠长度。使用 HE 染色观察小鼠结肠的组织病理学变化，使用 ELISA 检测血清中 IL-1β、TNF-α 和 IFN-γ的表达水平。为了研究缓解 CRC 进展的具体机制，我们使用 16S rRNA 扩增子测序和非靶向代谢组学研究肠道微生物的变化，使用真核转录组学评估与 CRC 相关的基因变化。结果表明，高剂量的活菌和热处理的 Zhang-LL 株均能显著抑制肿瘤发生、结肠缩短、不良炎症反应、肠道组织损伤和促炎因子表达上调。具体而言，在肠道微生物群中，调节了优势菌群 和 的丰度，显著降低了 PGE2 的表达，抑制了花生四烯酸代谢途径，上调了 CD22 介导的 B 细胞受体调节相关基因的表达。本研究表明，Zhang-LL 活菌或热处理株通过减少潜在致病菌的丰度、增加有益共生菌的丰度、调节花生四烯酸代谢途径和改善宿主免疫原性来缓解 CRC 的进展。
