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, Yu-Jui Yvonne Wan

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)246-254
Number of pages9
JournalJournal of Nutritional Biochemistry
Volume57
DOIs
StatePublished - Jul 1 2018

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Synbiotics
Nutrition
Oligosaccharides
Knockout Mice
Milk
Bile Acids and Salts
Neoplasms
Liver
Cholesterol
Detoxification
Western Diet
Bifidobacterium longum subspecies infantis
Non-alcoholic Fatty Liver Disease
Triglycerides
Insulin Resistance
Insulin
Membranes
Inflammation

Keywords

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

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

Cite this

Synbiotics Bifidobacterium infantis and milk oligosaccharides are effective in reversing cancer-prone nonalcoholic steatohepatitis using western diet-fed FXR knockout mouse models. / Jena, Prasant Kumar; Sheng, Lili; Nagar, Nidhi; Wu, Chao; Barile, Daniela; Mills, David A.; Wan, Yu-Jui Yvonne.

In: Journal of Nutritional Biochemistry, Vol. 57, 01.07.2018, p. 246-254.

Research output: Contribution to journalArticle

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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.",
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