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肠道细菌会产生次级胆汁酸,并影响无菌小鼠的肝脏生理机能。

The gut bacterium produces secondary bile acids and influences liver physiology in gnotobiotic mice.

机构信息

Functional Microbiome Research Group, Institute of Medical Microbiology, University Hospital of RWTH , Aachen, Germany.

Department of Molecular Systems Biology, Helmholtz-Centre for Environmental Research , Leipzig, Germany.

出版信息

Gut Microbes. 2021 Jan-Dec;13(1):1-21. doi: 10.1080/19490976.2020.1854008.

Abstract

is a newly described mouse gut bacterium which metabolizes cholic acid (CA) to deoxycholic acid (DCA) via 7α-dehydroxylation. Although bile acids influence metabolic and inflammatory responses, few models exist for studying their metabolism and impact on the host. Mice were colonized from birth with the simplified community Oligo-MM with or without . As the metabolism of bile acids is known to affect lipid homeostasis, mice were fed either a low- or high-fat diet for eight weeks before sampling and analyses targeting the gut and liver. Multiple Oligo-MM strains were capable of deconjugating primary bile acids produced DCA from CA either as pure compound or in mouse bile. This production was inducible by CA . Ursodeoxycholic, chenodeoxycholic, and β-muricholic acid were not metabolized under the conditions tested. All gnotobiotic mice were stably colonized with , which showed higher relative abundances after HF diet feeding. The presence of had minor, diet-dependent effects on Oligo-MM communities. The secondary bile acids DCA and surprisingly LCA and their taurine conjugates were detected exclusively in -colonized mice. colonization did not influence body weight, white adipose tissue mass, liver histopathology, hepatic aspartate aminotransferase, or blood levels of cholesterol, insulin, and paralytic peptide (PP). However, proteomics revealed shifts in hepatic pathways involved in amino acid, glucose, lipid, energy, and drug metabolism in -colonized mice. Liver fatty acid composition was substantially altered by dietary fat but not by In summary, stably colonized the gut of mice harboring a simplified community and produced secondary bile acids, which affected proteomes in the liver. This new gnotobiotic mouse model can now be used to study the pathophysiological role of secondary bile acids .

摘要

是一种新描述的鼠肠道细菌,通过 7α-脱羟化作用将胆酸(CA)代谢为脱氧胆酸(DCA)。尽管胆汁酸会影响代谢和炎症反应,但用于研究其代谢和对宿主影响的模型很少。通过出生时定植,用或不用 使小鼠定植简化的社区 Oligo-MM。由于胆汁酸的代谢已知会影响脂质稳态,因此在采样和针对肠道和肝脏的分析之前,小鼠被喂食低脂肪或高脂肪饮食 8 周。多种 Oligo-MM 菌株能够使初级胆汁酸去共轭,从 CA 中产生 DCA,无论是作为纯化合物还是在小鼠胆汁中。这种产生可被 CA 诱导。熊脱氧胆酸、鹅脱氧胆酸和β-鼠胆酸在测试条件下不会代谢。所有无菌小鼠均稳定定植于 ,在高脂饮食喂养后其相对丰度更高。 的存在对 Oligo-MM 群落有轻微的、依赖于饮食的影响。在 -定植的小鼠中仅检测到次级胆汁酸 DCA 和令人惊讶的 LCA 及其牛磺酸缀合物。 定植不会影响体重、白色脂肪组织质量、肝组织病理学、肝天冬氨酸氨基转移酶或胆固醇、胰岛素和麻痹肽 (PP) 的血液水平。然而,蛋白质组学揭示了 -定植小鼠中涉及氨基酸、葡萄糖、脂质、能量和药物代谢的肝途径发生了变化。肝脏脂肪酸组成因饮食脂肪而发生重大改变,但不受影响。总之, 稳定定植于携带简化群落的小鼠肠道,并产生次级胆汁酸,这影响了肝脏的蛋白质组。这种新的无菌小鼠模型现在可用于研究次级胆汁酸的病理生理作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ba8/7781625/5846ae950e4d/KGMI_A_1854008_F0001_OC.jpg

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