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

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

Author information

1
Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento 95817, CA, USA.
2
Research and Development, Hilmar Ingredients, Hilmar 95324, CA, USA.
3
Department of Food Science and Technology, University of California, Davis 95616, CA, USA.
4
Department of Food Science and Technology, University of California, Davis 95616, CA, USA; Department of Viticulture and Enology, University of California, Davis 95616, CA, USA.
5
Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento 95817, CA, USA. Electronic address: yjywan@ucdavis.edu.

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.

KEYWORDS:

Bile acid; Dysbiosis; Liver cancer; Microbiota; Prebiotics; Probiotics; TGR5

PMID:
29800811
PMCID:
PMC6015547
DOI:
10.1016/j.jnutbio.2018.04.007
[Indexed for MEDLINE]
Free PMC Article

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