Gut microbiota–regulated bile acids metabolism features in the aging process in mice

Kechun CHEN , Yating ZHAO , Lexun WANG , Yifan YIN , Ling YANG , Duosheng LUO
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Abstract

Objective

Aging is typically characterized by imbalanced gut microbiota and bile acid (BA) dyshomeostasis. However, features of the gut microbiota-regulated BA metabolism in the aging process remain unclear.

Aim

To establish a direct link between gut microbiota and BA profile changes in the liver, plasma, and intestinal contents and to further understand aging and aging-related diseases from the liver-gut axis.

Methods

The BA content in the liver, plasma, and intestine were determined using ultra-performance liquid chromatography-tandem mass spectrometry. Gut microbiota were sequenced by 16S rDNA, and the expression of the liver-gut axis-related proteins was detected.

Results

The plasma content of total cholesterol, triglycerides, and low-density lipoprotein cholesterol gradually increased during aging, and Lactobacillus, Bacteroides, Bacillus, Ruminococcus, Blautia, and Streptococcus, which can produce bile salt hydrolase, were increased. The concentration of total BAs was increased, especially that of unconjugated BAs, and the ratio of unconjugated BAs to conjugated BAs was also increased. The expression of bile acid transporter receptors and intestinal tight junction proteins was significantly decreased.

Conclusion

The presented data show that the changes in BA profile mediated by gut microbiota were closely related to aging and highlights that more attention should be paid to targeting gut microbiota-regulated BA metabolism to prevent and treat aging-related diseases, especially lipid metabolism disorders.

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小鼠衰老过程中肠道菌群调节胆汁酸代谢特征
衰老的典型特征是肠道菌群失衡和胆汁酸(BA)失衡。然而,肠道菌群调控BA代谢在衰老过程中的特点尚不清楚。目的建立肠道微生物群与肝脏、血浆和肠道内容物中BA谱变化的直接联系,从肝-肠轴进一步了解衰老和衰老相关疾病。方法采用超高效液相色谱-串联质谱法测定肝脏、血浆和肠道中的BA含量。采用16S rDNA对肠道菌群进行测序,检测肝肠轴相关蛋白的表达。结果随着年龄增长,血浆总胆固醇、甘油三酯、低密度脂蛋白胆固醇含量逐渐升高,产生胆汁盐水解酶的乳杆菌、拟杆菌、芽孢杆菌、瘤胃球菌、蓝索菌和链球菌含量升高。总BAs浓度增加,特别是未共轭BAs浓度增加,未共轭BAs与共轭BAs的比值也增加。胆汁酸转运受体和肠紧密连接蛋白的表达显著降低。结论肠道菌群介导的BA谱变化与衰老密切相关,应重视针对肠道菌群调节的BA代谢来预防和治疗衰老相关疾病,特别是脂质代谢紊乱。
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