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

Prasant Kumar Jena; Lili Sheng; Nidhi Nagar; Chao Wu; Daniela Barile; David A Mills; Yui-Jui Yvonne Wan

doi:10.1016/j.jnutbio.2018.04.007

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

Authors

Prasant Kumar Jena¹, Lili Sheng¹, Nidhi Nagar¹, Chao Wu², Daniela Barile³, David A Mills⁴, Yui-Jui Yvonne Wan⁵

Affiliations

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Bifidobacterium longum subspecies infantis*
Bile Acids and Salts / metabolism
Diet, Western / adverse effects
Disease Models, Animal
Female
Male
Mice, Inbred C57BL
Mice, Knockout
Milk / chemistry*
Non-alcoholic Fatty Liver Disease / diet therapy*
Non-alcoholic Fatty Liver Disease / metabolism
Oligosaccharides / pharmacology*
Receptors, Cytoplasmic and Nuclear / genetics
Receptors, G-Protein-Coupled / metabolism
Synbiotics*

Substances

Bile Acids and Salts
Gpbar1 protein, mouse
Oligosaccharides
Receptors, Cytoplasmic and Nuclear
Receptors, G-Protein-Coupled
farnesoid X-activated receptor

Abstract

Publication types

MeSH terms

Substances

Grants and funding