Abstract

Akkermansia muciniphila is a prominent member of the gut microbiota and the organism gets exposed to bile acids within this niche. Several gut bacteria have bile response genes to metabolize bile acids or an ability to change their membrane structure to prevent membrane damage from bile acids. To understand the response to bile acids and how A. muciniphila can persist in the gut, we studied the effect of bile acids and individual bile salts on growth. In addition, the change in gene expression under ox-bile condition was studied. The growth of A. muciniphila was inhibited by ox-bile and the bile salts mixture. Individual bile salts have differential effects on the growth. Although most bile salts inhibited the growth of A. muciniphila, an increased growth was observed under culture conditions with sodium deoxycholate. Zaragozic acid A, which is a squalene synthase inhibitor leading to changes in the membrane structure, increased the susceptibility of A. muciniphila to bile acids. Transcriptome analysis showed that gene clusters associated with an ABC transporter and RND transporter were upregulated in the presence of ox-bile. In contrast, a gene cluster containing a potassium transporter was downregulated. Membrane transporter inhibitors also decreased the tolerance to bile acids of A. muciniphila. Our results indicated that membrane transporters and the squalene-associated membrane structure could be major bile response systems required for bile tolerance in A. muciniphila.

Key points

• The growth of Akkermansia muciniphila was inhibited by most bile salts.

• Sodium deoxycholate increased the growth of A. muciniphila.

• The genes encoding transporters and hopanoid synthesis were upregulated by ox-bile.

• The inhibitors of transporters and hopanoid synthesis reduced ox-bile tolerance.

中文翻译：

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胆汁酸对黏液阿克曼草生长和整体基因表达谱的影响

摘要

Akkermansia muciniphila是肠道菌群的重要成员，该生物体暴露于该生态位内的胆汁酸。几种肠道细菌具有胆汁反应基因来代谢胆汁酸，或者具有改变其膜结构以防止胆汁酸损害膜的能力。要理解到胆汁酸以及如何应对一个。粘液菌可以在肠道中持续存在，我们研究了胆汁酸和胆汁盐对生长的影响。另外，研究了在牛胆条件下基因表达的变化。A的生长。黏液菌被牛胆汁和胆盐混合物抑制。个别的胆汁盐对生长有不同的影响。尽管大多数胆汁盐会抑制胆汁的生长一。粘菌，在培养条件下用脱氧胆酸钠可以观察到生长的增加。Zaragozic acid A是一种鲨烯合酶抑制剂，可导致膜结构发生变化，从而增加了A的敏感性。粘菌对胆汁酸。转录组分析显示，在牛胆汁存在下，与ABC转运蛋白和RND转运蛋白相关的基因簇被上调。相反，含有钾转运蛋白的基因簇被下调。膜转运蛋白抑制剂还降低了A对胆汁酸的耐受性。梅毒。我们的结果表明，膜转运蛋白和角鲨烯相关的膜结构可能是黏液曲霉对胆汁耐受的主要胆汁反应系统。

关键点

•大多数胆汁盐都抑制了阿克尔曼丝菌的生长。

•脱氧胆酸钠可以增加黏液曲霉的生长。

•牛胆汁上调了编码转运蛋白和类胡萝卜素合成的基因。

•转运蛋白和类胡萝卜素合成的抑制剂降低了牛胆汁的耐受性。