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合生素双歧杆菌和乳寡糖可有效逆转 FXR 基因敲除小鼠模型的非酒精性脂肪性肝炎。

Synbiotics Bifidobacterium infantis and milk oligosaccharides are effective in reversing cancer-prone nonalcoholic steatohepatitis using western diet-fed FXR knockout mouse models.

机构信息

Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento 95817, CA, USA.

Research and Development, Hilmar Ingredients, Hilmar 95324, CA, USA.

出版信息

J Nutr Biochem. 2018 Jul;57:246-254. doi: 10.1016/j.jnutbio.2018.04.007. Epub 2018 Apr 25.

DOI:10.1016/j.jnutbio.2018.04.007
PMID:29800811
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6015547/
Abstract

Milk oligosaccharides (MO) selectively increase the growth of Bifidobacterium infantis (B. infantis). This study examines the effects of bovine MO and B. infantis in preventing nonalcoholic steatohepatitis (NASH) in Western diet (WD)-fed bile acid (BA) receptor FXR (farnesoid x receptor) knockout (KO) mice. WD-fed FXR KO mice have cancer-prone NASH and reduced B. infantis. MO and/or B. infantis supplementation improved their insulin sensitivity and reduced hepatic inflammation. Additionally, B. infantis, but not MO, decreased hepatic triglyceride and cholesterol. A combination of both further reduced hepatic cholesterol, the precursor of BAs. All three treatments modulated serum and hepatic BA profile. Moreover, B. infantis and MO decreased hepatic CYP7A1 and induced Sult2a1, Sult2a2, and Sult2a3 suggesting reduced BA synthesis and increased detoxification. Furthermore, B. infantis and MO increased ileal BA membrane receptor TGR5-regulated signaling. Together, via BA-regulated signaling, synbiotics B. infantis and MO have their unique and combined effects in reversing NASH.

摘要

牛奶低聚糖（MO）选择性地增加婴儿双歧杆菌（B. infantis）的生长。本研究探讨了牛 MO 和 B. infantis 在预防西方饮食（WD）喂养的胆汁酸（BA）受体法尼醇 X 受体（FXR）敲除（KO）小鼠非酒精性脂肪性肝炎（NASH）中的作用。WD 喂养的 FXR KO 小鼠易患癌症的 NASH 和减少的 B. infantis。MO 和/或 B. infantis 补充改善了它们的胰岛素敏感性并减少了肝炎症。此外，B. infantis 但不是 MO，降低了肝甘油三酯和胆固醇。两者的组合进一步降低了肝脏胆固醇，BA 的前体。这三种治疗方法都调节了血清和肝脏 BA 谱。此外，B. infantis 和 MO 降低了肝 CYP7A1 并诱导了 Sult2a1、Sult2a2 和 Sult2a3，表明 BA 合成减少和解毒增加。此外，B. infantis 和 MO 增加了回肠 BA 膜受体 TGR5 调节的信号转导。总之，通过 BA 调节的信号转导，合生元 B. infantis 和 MO 在逆转 NASH 方面具有独特和联合的作用。

相似文献

[1]
Synbiotics Bifidobacterium infantis and milk oligosaccharides are effective in reversing cancer-prone nonalcoholic steatohepatitis using western diet-fed FXR knockout mouse models.

J Nutr Biochem. 2018-4-25

[2]
The effect of synbiotics and milk oligosaccharides on shaping gut microbiota community structure and NASH treatment.

Data Brief. 2018-5-24

[3]
The role of FXR and TGR5 in reversing and preventing progression of Western diet-induced hepatic steatosis, inflammation, and fibrosis in mice.

J Biol Chem. 2022-11

[4]
Hepatic inflammation caused by dysregulated bile acid synthesis is reversible by butyrate supplementation.

J Pathol. 2017-12

[5]
Dysregulated FXR-FGF19 signaling and choline metabolism are associated with gut dysbiosis and hyperplasia in a novel pig model of pediatric NASH.

Am J Physiol Gastrointest Liver Physiol. 2020-1-31

[6]
Assessment of the synbiotic properites of human milk oligosaccharides and Bifidobacterium longum subsp. infantis in vitro and in humanised mice.

Benef Microbes. 2017-1-24

[7]
Western Diet-Induced Dysbiosis in Farnesoid X Receptor Knockout Mice Causes Persistent Hepatic Inflammation after Antibiotic Treatment.

Am J Pathol. 2017-8

[8]
Bile acids contribute to the development of non-alcoholic steatohepatitis in mice.

JHEP Rep. 2021-10-13

[9]
Inhibition of ileal bile acid uptake protects against nonalcoholic fatty liver disease in high-fat diet-fed mice.

Sci Transl Med. 2016-9-21

[10]
Western diet-induced increase in colonic bile acids compromises epithelial barrier in nonalcoholic steatohepatitis.

FASEB J. 2020-5

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[2]
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Pharmaceuticals (Basel). 2024-8-30

[3]
Targeting stroma and tumor, silencing galectin 1 treats orthotopic mouse hepatocellular carcinoma.

Acta Pharm Sin B. 2024-1

[4]
Non-alcoholic Steatohepatitis in Asians: Current Perspectives and Future Directions.

Cureus. 2023-8-2

[5]
Hepatic Transcriptomics Reveals Reduced Lipogenesis in High-Salt Diet Mice.

Genes (Basel). 2023-4-24

[6]
Translating neonatal microbiome science into commercial innovation: metabolism of human milk oligosaccharides as a basis for probiotic efficacy in breast-fed infants.

Gut Microbes. 2023

[7]
The promising role of probiotics/prebiotics/synbiotics in energy metabolism biomarkers in patients with NAFLD: A systematic review and meta-analysis.

Front Public Health. 2022

[8]
Crosstalk Between the Gut and Brain: Importance of the Fecal Microbiota in Patient With Brain Tumors.

Front Cell Infect Microbiol. 2022

[9]
Dietary Fiber to Starch Ratio Affects Bovine Milk Oligosaccharide Profiles.

Curr Dev Nutr. 2022-3-7

[10]
The Role of the Intestinal Microbiota in Nonalcoholic Steatohepatitis.

Front Endocrinol (Lausanne). 2022

本文引用的文献

[1]
Intestine farnesoid X receptor agonist and the gut microbiota activate G-protein bile acid receptor-1 signaling to improve metabolism.

Hepatology. 2018-5-21

[2]
Dysregulated bile acid synthesis and dysbiosis are implicated in Western diet-induced systemic inflammation, microglial activation, and reduced neuroplasticity.

FASEB J. 2018-1-10

[3]
Bile acid metabolism and signaling in liver disease and therapy.

Liver Res. 2017-6

[4]
Hepatic inflammation caused by dysregulated bile acid synthesis is reversible by butyrate supplementation.

J Pathol. 2017-12

[5]
Western Diet-Induced Dysbiosis in Farnesoid X Receptor Knockout Mice Causes Persistent Hepatic Inflammation after Antibiotic Treatment.

Am J Pathol. 2017-8

[6]
Tolerability and safety of the intake of bovine milk oligosaccharides extracted from cheese whey in healthy human adults.

J Nutr Sci. 2017-2-20

[7]
Gender Differences in Bile Acids and Microbiota in Relationship with Gender Dissimilarity in Steatosis Induced by Diet and FXR Inactivation.

Sci Rep. 2017-5-11

[8]
Farnesoid X receptor induces Takeda G-protein receptor 5 cross-talk to regulate bile acid synthesis and hepatic metabolism.

J Biol Chem. 2017-6-30

[9]
Identification and characterization of a novel PPARα-regulated and 7α-hydroxyl bile acid-preferring cytosolic sulfotransferase mL-STL (Sult2a8).

J Lipid Res. 2017-6

[10]
Prebiotic milk oligosaccharides prevent development of obese phenotype, impairment of gut permeability, and microbial dysbiosis in high fat-fed mice.

Am J Physiol Gastrointest Liver Physiol. 2017-5-1

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