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肠道微生物组 Turicibacter 菌株差异地调节胆汁酸和宿主脂质。

Gut microbiota Turicibacter strains differentially modify bile acids and host lipids.

机构信息

Department of Integrative Biology & Physiology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.

Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.

出版信息

Nat Commun. 2023 Jun 20;14(1):3669. doi: 10.1038/s41467-023-39403-7.

Abstract

Bacteria from the Turicibacter genus are prominent members of the mammalian gut microbiota and correlate with alterations in dietary fat and body weight, but the specific connections between these symbionts and host physiology are poorly understood. To address this knowledge gap, we characterize a diverse set of mouse- and human-derived Turicibacter isolates, and find they group into clades that differ in their transformations of specific bile acids. We identify Turicibacter bile salt hydrolases that confer strain-specific differences in bile deconjugation. Using male and female gnotobiotic mice, we find colonization with individual Turicibacter strains leads to changes in host bile acid profiles, generally aligning with those produced in vitro. Further, colonizing mice with another bacterium exogenously expressing bile-modifying genes from Turicibacter strains decreases serum cholesterol, triglycerides, and adipose tissue mass. This identifies genes that enable Turicibacter strains to modify host bile acids and lipid metabolism, and positions Turicibacter bacteria as modulators of host fat biology.

摘要

瘤胃菌属的细菌是哺乳动物肠道微生物群的主要成员,与饮食中脂肪和体重的变化相关,但这些共生体与宿主生理学之间的具体联系还知之甚少。为了解决这一知识空白,我们对一系列来自小鼠和人类的不同 Turicibacter 分离株进行了表征,发现它们分为不同的进化枝,在特定胆汁酸的转化上存在差异。我们鉴定了 Turicibacter 胆汁盐水解酶,这些酶赋予了菌株在胆汁去共轭化上的特异性差异。使用雄性和雌性无菌小鼠,我们发现单个 Turicibacter 菌株的定植会导致宿主胆汁酸谱发生变化,通常与体外产生的变化一致。此外,用另一种细菌定植,该细菌从 Turicibacter 菌株中外源表达改变胆汁的基因,会降低血清胆固醇、甘油三酯和脂肪组织质量。这确定了使 Turicibacter 菌株能够改变宿主胆汁酸和脂质代谢的基因,并将 Turicibacter 细菌定位为宿主脂肪生物学的调节剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a76/10281990/7964e5af8697/41467_2023_39403_Fig1_HTML.jpg

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