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由健康人体肠道微生物群中分离出的大肠杆菌产生的短链脂肪酸的抗癌和抗炎作用。

Anti-cancer and anti-inflammatory effects elicited by short chain fatty acids produced by Escherichia coli isolated from healthy human gut microbiota.

机构信息

Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.

Department of Biotechnology, Faculty of Agro-Industry, Kasetsart University, Chatuchak, 10900, Bangkok, Thailand.

出版信息

Microb Cell Fact. 2021 Feb 5;20(1):36. doi: 10.1186/s12934-020-01477-z.

Abstract

BACKGROUND

Extracellular metabolites of short chain fatty acids (SCFA) excreted by gut microbiota have been reported to play an important role in the regulation of intestinal homeostasis. Apart from supplying energy, SCFA also elicit immune stimulation in animal and human cells. Therefore, an attempt was conducted to isolate SCFA producing bacteria from healthy human microbiota. The anti-cancer and anti-inflammatory effects of extracellular metabolites and individual SFCA were further investigated by using breast, colon cancer and macrophage cells. Toxin, inflammatory and anti-inflammatory cytokine gene expressions were investigated by RT-qPCR analyses in this study.

RESULTS

Escherichia coli KUB-36 was selected in this study since it has the capability to produce seven SCFA extracellularly. It produced acetic acid as the main SCFA. It is a non-exotoxin producer and hence, it is a safe gut microbiota. The IC values indicated that the E. coli KUB-36 metabolites treatment elicited more potent cytotoxicity effect on MCF7 breast cancer cell as compared to colon cancer and leukemia cancer cells but exhibited little cytotoxic effects on normal breast cell. Furthermore, E. coli KUB-36 metabolites and individual SCFA could affect inflammatory responses in lipopolysaccharide-induced THP-1 macrophage cells since they suppressed inflammatory cytokines IL-1β, IL-6, IL-8 and TNF-α well as compared to the control, whilst inducing anti-inflammatory cytokine IL-10 expression.

CONCLUSION

SCFA producing E. coli KUB-36 possessed vast potential as a beneficial gut microbe since it is a non-exotoxin producer that exhibited beneficial cytotoxic effects on cancer cells and elicited anti-inflammatory activity simultaneously. However, the probiotic characteristic of E. coli KUB-36 should be further elucidated using in vivo animal models.

摘要

背景

肠道微生物群产生的短链脂肪酸(SCFA)的细胞外代谢物已被报道在调节肠道稳态中发挥重要作用。除了提供能量外,SCFA 还在动物和人类细胞中引起免疫刺激。因此,尝试从健康人体微生物群中分离产生 SCFA 的细菌。通过使用乳腺癌、结肠癌和巨噬细胞细胞,进一步研究了细胞外代谢物和单个 SCFA 的抗癌和抗炎作用。本研究通过 RT-qPCR 分析研究了毒素、炎症和抗炎细胞因子基因的表达。

结果

本研究选择了大肠杆菌 KUB-36,因为它具有体外产生七种 SCFA 的能力。它产生乙酸作为主要的 SCFA。它不是外毒素产生菌,因此是一种安全的肠道微生物群。IC 值表明,与结肠癌和白血病细胞相比,大肠杆菌 KUB-36 代谢物处理对 MCF7 乳腺癌细胞的细胞毒性作用更强,但对正常乳腺细胞的细胞毒性作用较小。此外,大肠杆菌 KUB-36 代谢物和单个 SCFA 可影响脂多糖诱导的 THP-1 巨噬细胞中的炎症反应,因为它们抑制炎症细胞因子 IL-1β、IL-6、IL-8 和 TNF-α的表达,与对照组相比,同时诱导抗炎细胞因子 IL-10 的表达。

结论

产生 SCFA 的大肠杆菌 KUB-36 作为有益的肠道微生物具有巨大的潜力,因为它是一种非外毒素产生菌,对癌细胞具有有益的细胞毒性作用,并同时具有抗炎活性。然而,应该使用体内动物模型进一步阐明大肠杆菌 KUB-36 的益生菌特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7251/7863513/0e40d148927d/12934_2020_1477_Fig1_HTML.jpg

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