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通过调节肠道微生物组和代谢组缓解 AOM/DSS 处理的小鼠的炎症和结肠癌症状。

-12 Alleviates Inflammation and Colon Cancer Symptoms in AOM/DSS-Treated Mice through Modulating the Intestinal Microbiome and Metabolome.

机构信息

School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China.

Dalian Probiotics Function Research Key Laboratory, Dalian Polytechnic University, Dalian 116034, China.

出版信息

Nutrients. 2022 May 3;14(9):1916. doi: 10.3390/nu14091916.

DOI:10.3390/nu14091916
PMID:35565884
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9100115/
Abstract

In our previous research, Lactiplantibacillus plantarum-12 alleviated inflammation in dextran sodium sulfate (DSS)-induced mice by regulating intestinal microbiota and preventing colon shortening (p < 0.05). The purpose of the present study was to evaluate whether L. plantarum-12 could ameliorate the colon cancer symptoms of azoxymethane (AOM)/DSS-treated C57BL/6 mice. The results showed that L. plantarum-12 alleviated colonic shortening (from 7.43 ± 0.15 to 8.23 ± 0.25) and weight loss (from 25.92 ± 0.21 to 27.75 ± 0.88) in AOM/DSS-treated mice. L. plantarum-12 oral administration down-regulated pro-inflammatory factors TNF-α (from 350.41 ± 15.80 to 247.72 ± 21.91), IL-8 (from 322.19 ± 11.83 to 226.08 ± 22.06), and IL-1β (111.43 ± 8.14 to 56.90 ± 2.70) levels and up-regulated anti-inflammatory factor IL-10 (from 126.08 ± 24.92 to 275.89 ± 21.87) level of AOM/DSS-treated mice. L. plantarum-12 oral administration restored the intestinal microbiota dysbiosis of the AOM/DSS treated mice by up-regulating beneficial Muribaculaceae, Lactobacillaceae, and Bifidobacteriaceae levels and down-regulating pathogenic Proteobacteria, Desulfovibrionaceae, and Erysipelotrichaceae levels. As a result, the fecal metabolites of the AOM/DSS-treated mice were altered, including xanthosine, uridine, 3,4-methylenesebacic acid, 3-hydroxytetradecanedioic acid, 4-hydroxyhexanoylglycine, beta-leucine, and glycitein, by L. plantarum-12 oral administration. Furthermore, L. plantarum-12 oral administration significantly ameliorated the colon injury of the AOM/DSS-treated mice by enhancing colonic tight junction protein level and promoting tumor cells death via down-regulating PCNA (proliferating cell nuclear antigen) and up-regulating pro-apoptotic Bax. (p < 0.05). Taken together, L. plantarum-12 oral administration could ameliorate the colon cancer burden and inflammation of AOM-DSS-treated C57BL/6 mice through regulating the intestinal microbiota, manipulating fecal metabolites, enhancing colon barrier function, and inhibiting NF-κB signaling. These results suggest that L. plantarum-12 might be an excellent probiotic candidate for the prevention of colon cancer.

摘要

在我们之前的研究中,植物乳杆菌 -12 通过调节肠道微生物群和防止结肠缩短来减轻葡聚糖硫酸钠(DSS)诱导的小鼠的炎症(p<0.05)。本研究旨在评估植物乳杆菌 -12 是否可以改善氧化偶氮甲烷(AOM)/DSS 处理的 C57BL/6 小鼠的结肠癌症状。结果表明,植物乳杆菌 -12 减轻了 AOM/DSS 处理小鼠的结肠缩短(从 7.43±0.15 至 8.23±0.25)和体重减轻(从 25.92±0.21 至 27.75±0.88)。植物乳杆菌 -12 口服给药下调促炎因子 TNF-α(从 350.41±15.80 至 247.72±21.91)、IL-8(从 322.19±11.83 至 226.08±22.06)和 IL-1β(111.43±8.14 至 56.90±2.70)水平,并上调抗炎因子 IL-10(从 126.08±24.92 至 275.89±21.87)水平。植物乳杆菌 -12 口服给药通过上调有益的 Muribaculaceae、Lactobacillaceae 和 Bifidobacteriaceae 水平和下调致病的 Proteobacteria、Desulfovibrionaceae 和 Erysipelotrichaceae 水平,恢复了 AOM/DSS 处理小鼠的肠道微生物失调。结果,AOM/DSS 处理小鼠的粪便代谢物发生变化,包括黄嘌呤核苷、尿苷、3,4-亚甲基癸二酸、3-羟基十四烷二酸、4-羟基己酰甘氨酸、β-亮氨酸和大豆苷元,这是通过植物乳杆菌 -12 口服给药实现的。此外,植物乳杆菌 -12 口服给药通过增强结肠紧密连接蛋白水平和通过下调 PCNA(增殖细胞核抗原)和上调促凋亡 Bax 来促进肿瘤细胞死亡,显著改善了 AOM/DSS 处理小鼠的结肠损伤(p<0.05)。综上所述,植物乳杆菌 -12 通过调节肠道微生物群、操纵粪便代谢物、增强结肠屏障功能和抑制 NF-κB 信号通路,可减轻 AOM-DSS 处理的 C57BL/6 小鼠的结肠癌负担和炎症。这些结果表明,植物乳杆菌 -12 可能是预防结肠癌的优秀益生菌候选物。

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