胆汁酸生理功能及其与肠道微生物互作研究进展

doi:10.13560/j.cnki.biotech.bull.1985.2022-0931

摘要/Abstract

摘要：

胆汁酸（bile acids, BAs）是由胆固醇代谢产生的，在肝脏中胆固醇转化为初级胆汁酸，进入肠道后又经肠道菌群代谢为次级胆汁酸，并通过肠肝循环在体内维持稳态。胆汁酸分子既有亲水端又有亲脂端的结构，可发挥洗涤剂的作用，有助于溶解和吸收膳食中的脂类及脂溶性维生素等，这也使得胆汁酸具有一定的抗菌特性。胆汁酸与肠道菌群的互作不仅体现在其自身的生理功能上，而且肠道细菌的组成及数量也调控着胆汁酸代谢，并通过激活不同的受体信号调节糖脂代谢、能量代谢以及免疫炎症反应等。本文综述了胆汁酸的代谢过程及其如何通过FXR、TGR5等受体信号调控宿主生理功能等，为后续通过科学合理地调控肠道菌群及其代谢物来维护动物健康、促进畜禽生产提供参考。

关键词: 胆汁酸, 肠道菌群, 生理功能, 互作

Abstract:

Bile acids（BAs）are produced from the metabolism of cholesterol. In the liver, cholesterol is converted into primary bile acids，and they are metabolized into secondary bile acids by gut microbiota when they reache the intestinal tract. Their homeostasis are maintained in the body through the enterohepatic circulation. The molecules of bile acids have both hydrophilic and lipophilic ends, which can play the role of detergent and help to dissolve and absorb dietary lipids and lipid-soluble vitamins. This also endows bile acids with certain antibacterial properties. The interaction between bile acids and gut microbiota is not only reflected in their own physiological functions of bile acids, but also in the regulations of the gut microbial composition and abundances in bile acid metabolism. Bile acids regulate glucose, lipid and energy metabolisms, and immune and inflammatory reactions by activating different receptor signal pathways. This article reviews the metabolic process of bile acids, and discusses how it regulates host physiological functions through FXR, TGR5 and other receptor signal pathways. It also provides references for maintaining animal health and promoting livestock and poultry production performance through scientifically and reasonably regulating gut microbiota and its metabolites.

Key words: bile acids, gut microbiota, physiological function, interaction

熊淑琪. 胆汁酸生理功能及其与肠道微生物互作研究进展[J]. 生物技术通报, 2023, 39(4): 187-200.

XIONG Shu-qi. Towards the Understanding on the Physiological Functions of Bile Acids and Interactions with Gut Microbiota[J]. Biotechnology Bulletin, 2023, 39(4): 187-200.

图/表 4

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物种Species	初级胆汁酸Primary bile acids		次级胆汁酸Secondary bile acids
物种Species	游离型Free	结合型Conjugated	游离型Free	结合型Conjugated
人	胆酸、鹅脱氧胆酸	甘氨胆酸、甘氨鹅脱氧胆酸	石胆酸、脱氧胆酸	甘氨石胆酸、甘氨脱氧胆酸
啮齿动物（鼠）	α-鼠胆酸、β-鼠胆酸、胆酸	牛磺α/β-鼠胆酸、牛磺胆酸	ω-鼠胆酸、熊脱氧胆酸、石胆酸	牛磺ω-鼠胆酸、牛磺熊脱氧胆酸、牛磺石胆酸
猪	猪胆酸	甘氨/牛磺猪胆酸	猪脱氧胆酸	甘氨/牛磺猪脱氧胆酸

物种Species	初级胆汁酸Primary bile acids		次级胆汁酸Secondary bile acids
物种Species	游离型Free	结合型Conjugated	游离型Free	结合型Conjugated
人	胆酸、鹅脱氧胆酸	甘氨胆酸、甘氨鹅脱氧胆酸	石胆酸、脱氧胆酸	甘氨石胆酸、甘氨脱氧胆酸
啮齿动物（鼠）	α-鼠胆酸、β-鼠胆酸、胆酸	牛磺α/β-鼠胆酸、牛磺胆酸	ω-鼠胆酸、熊脱氧胆酸、石胆酸	牛磺ω-鼠胆酸、牛磺熊脱氧胆酸、牛磺石胆酸
猪	猪胆酸	甘氨/牛磺猪胆酸	猪脱氧胆酸	甘氨/牛磺猪脱氧胆酸

受体Receptor	胆汁酸配体Ligand bile acids		表达组织 Expressive tissues	作用途径Functional pathways
受体Receptor	激活剂 Activators	拮抗剂Antagonists	表达组织 Expressive tissues	作用途径Functional pathways
FXR	CDCA、CA、T（G）CDCA、T（G）CA、LCA、DCA、HCAs	TαMC、TβMCA UDCA、isoDCA	肝脏	胆汁酸代谢	FXR—SHP-1—LRH-1—抑制CYP7A1
				胆汁酸代谢	FXR—IR-1—激活胆汁酸转运载体蛋白
				脂代谢	FXR—SHP—SREBP-1c—抑制脂肪酸合成酶
					FXR—PPARα—促进脂肪酸氧化代谢
					FXR—ApoCII—LPL—促进甘油三酯水解
					FXR—p-JNK—HNF4α—SRB1—促进HDL-C清除
				糖代谢	FXR—SHP—抑制糖异生基因
				糖代谢	FXR—LPK—抑制糖酵解
			肠道	胆汁酸代谢	FXR—FGF19/15—结合肝脏FGFR4/βKlotho—激活JNK途径—抑制CYP7A1
				糖代谢	FXR—FGF19/15—结合肝脏FGFR4/βKlotho—抑制肝脏糖异生基因
				糖代谢	FXR—抑制GLP-1分泌
			免疫细胞	炎症反应	FXR—抑制促炎细胞因子的分泌
TGR5	T（G）LCA、LCA、T（G）DCA、DCA、CDCA、T（G）CDCA、TCA、CA、UDCA、HCAs		棕色脂肪组织	能量代谢	TGR5—cAMP—Dio2—增强能量消耗
			骨骼肌	能量代谢	TGR5—cAMP—Dio2—增强能量消耗
			免疫细胞	免疫反应	TGR5—cAMP—抑制NF-kB信号通路—抑制促炎细胞因子
			肠道	糖代谢	TGR5—cAMP—促进GLP-1分泌
			肠道	肠上皮稳态	调控肠道干细胞自我更新、增殖和分化

受体Receptor	胆汁酸配体Ligand bile acids		表达组织 Expressive tissues	作用途径Functional pathways
受体Receptor	激活剂 Activators	拮抗剂Antagonists	表达组织 Expressive tissues	作用途径Functional pathways
FXR	CDCA、CA、T（G）CDCA、T（G）CA、LCA、DCA、HCAs	TαMC、TβMCA UDCA、isoDCA	肝脏	胆汁酸代谢	FXR—SHP-1—LRH-1—抑制CYP7A1
				胆汁酸代谢	FXR—IR-1—激活胆汁酸转运载体蛋白
				脂代谢	FXR—SHP—SREBP-1c—抑制脂肪酸合成酶
					FXR—PPARα—促进脂肪酸氧化代谢
					FXR—ApoCII—LPL—促进甘油三酯水解
					FXR—p-JNK—HNF4α—SRB1—促进HDL-C清除
				糖代谢	FXR—SHP—抑制糖异生基因
				糖代谢	FXR—LPK—抑制糖酵解
			肠道	胆汁酸代谢	FXR—FGF19/15—结合肝脏FGFR4/βKlotho—激活JNK途径—抑制CYP7A1
				糖代谢	FXR—FGF19/15—结合肝脏FGFR4/βKlotho—抑制肝脏糖异生基因
				糖代谢	FXR—抑制GLP-1分泌
			免疫细胞	炎症反应	FXR—抑制促炎细胞因子的分泌
TGR5	T（G）LCA、LCA、T（G）DCA、DCA、CDCA、T（G）CDCA、TCA、CA、UDCA、HCAs		棕色脂肪组织	能量代谢	TGR5—cAMP—Dio2—增强能量消耗
			骨骼肌	能量代谢	TGR5—cAMP—Dio2—增强能量消耗
			免疫细胞	免疫反应	TGR5—cAMP—抑制NF-kB信号通路—抑制促炎细胞因子
			肠道	糖代谢	TGR5—cAMP—促进GLP-1分泌
			肠道	肠上皮稳态	调控肠道干细胞自我更新、增殖和分化