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乳酸双歧杆菌可改善AOM/DSS诱导的炎症、微生物群失调和结肠癌前病变。

Bifidobacterium lactis ameliorates AOM/DSS-induced inflammation, dysbiosis, and colonic precancerous lesions.

作者信息

Chan Yi-Lin, Liao Jun-Cheng, Li Tsung-Lin, Wu Chang-Jer, Chiu Yi-Han

机构信息

Department of Chemistry, Chinese Culture University, Taipei, Taiwan, ROC.

Department of Microbiology, Soochow University, 70, Linhsi Road, Taipei, Taiwan, ROC.

出版信息

Appl Microbiol Biotechnol. 2025 Mar 21;109(1):69. doi: 10.1007/s00253-025-13445-x.

Abstract

Bowel cancer is the third most common malignancy of tumors and one of the major causes of cancer-related death. Bowel precancerous conditions can develop without any symptoms, which either makes it difficult for early diagnosis or poses a poor prognosis/gloomy relapse. This study aimed to investigate the effects of Bifidobacterium animalis subsp. lactis TCI604 (B. lactis) on inflammatory responses, gut microbiome, and protectiveness against azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colonic precancerous lesions. The AOM/DSS-induced colonic precancerous lesion murine model was studied with 24 female C57BL/6 J mice assigned to the control group, AOM/DSS-induced colonic precancerous lesion group (AOM/DSS), AOM/DSS treated with B. lactis probiotic group (B. lactis P), and AOM/DSS treated with B. lactis cell-free supernatant group (B. lactis S). The results showed that both B. lactis P and B. lactis S could attenuate AOM/DSS-induced body weight loss and intestine damage, reduce aberrant crypt foci (ACF) and the formation of colonic polyps, and significantly inhibit pro-inflammatory cytokines and the NF-κB signaling pathway, in which the B. lactis S group outperformed others. Further analysis using 16S rDNA sequencing suggested that both B. lactis P and B. lactis S optimize gut microbiota. Several bacteria, including Muribaculaceae, Prevotellaceae_UCG-001, Anaerostipes, Ruminococcaceae, Mucispirillum, Clostridia_UCG-014, and Clostridia_vadinBB60 that were known in close relation to colonic precancerous lesions, were sequenced at taxonomic level. Our results indicated that both B. lactis P and B. lactis S improved AOM/DSS-induced colonic precancerous lesions by regulating inflammation as well as optimizing gut microbiota, thereby establishing reciprocally cooperative net benefits between probiotics/postbiotics and mice with colonic precancerous lesions. KEY POINTS: • Prophylactic administration of probiotic and postbiotic of B. lactis is capable of alleviating the AOM/DSS-induced body weight loss and colon shortening, as well as diminishing the development of colonic precancerous lesions, such as the formation of ACF and colonic polyps, in an AOM/DSS mouse model • Either probiotic or postbiotic of B. lactis has a positive role in mediating immune imbalance and colonic inflammation via suppression of inflammatory immune cells, pro-inflammatory cytokines, and the NF-κB signaling pathway • AOM/DSS-induced dysbiosis can be reversed with the probiotic and postbiotic of B. lactis supplementation.

摘要

肠癌是第三大常见肿瘤恶性疾病,也是癌症相关死亡的主要原因之一。肠道癌前病变可能在没有任何症状的情况下发展,这既使得早期诊断困难,也导致预后不良或复发风险高。本研究旨在探讨动物双歧杆菌乳亚种TCI604(B. lactis)对炎症反应、肠道微生物群的影响,以及对氧化偶氮甲烷(AOM)/葡聚糖硫酸钠(DSS)诱导的结肠前癌病变的保护作用。对AOM/DSS诱导的结肠前癌病变小鼠模型进行了研究,将24只雌性C57BL/6 J小鼠分为对照组、AOM/DSS诱导的结肠前癌病变组(AOM/DSS)、用B. lactis益生菌处理的AOM/DSS组(B. lactis P)和用B. lactis无细胞上清液处理的AOM/DSS组(B. lactis S)。结果表明,B. lactis P和B. lactis S均能减轻AOM/DSS诱导的体重减轻和肠道损伤,减少异常隐窝灶(ACF)和结肠息肉的形成,并显著抑制促炎细胞因子和NF-κB信号通路,其中B. lactis S组表现优于其他组。使用16S rDNA测序的进一步分析表明,B. lactis P和B. lactis S均能优化肠道微生物群。对几种与结肠前癌病变密切相关的细菌,包括毛螺菌科、普雷沃氏菌科_UCG-001、厌氧棒菌属、瘤胃球菌科、黏液螺旋菌属、梭菌纲_UCG-014和梭菌纲_vadinBB60,在分类水平上进行了测序。我们的结果表明,B. lactis P和B. lactis S均通过调节炎症以及优化肠道微生物群改善了AOM/DSS诱导的结肠前癌病变,从而在益生菌/后生元与结肠前癌病变小鼠之间建立了相互合作的净效益。关键点:• 在AOM/DSS小鼠模型中,预防性给予B. lactis益生菌和后生元能够减轻AOM/DSS诱导的体重减轻和结肠缩短,并减少结肠前癌病变的发展,如ACF和结肠息肉的形成• B. lactis的益生菌或后生元通过抑制炎性免疫细胞、促炎细胞因子和NF-κB信号通路,在介导免疫失衡和结肠炎症方面具有积极作用• 补充B. lactis的益生菌和后生元可以逆转AOM/DSS诱导的肠道菌群失调

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2478/11928396/632355626c6d/253_2025_13445_Fig1_HTML.jpg

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