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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.

Research Insights

SupplementHealth OutcomeEffect TypeEffect Size
Bifidobacterium infantis M-63Enhanced DetoxificationBeneficial
Bifidobacterium infantis M-63Enhanced TGR5 SignalingBeneficial
Bifidobacterium infantis M-63Improved Insulin SensitivityBeneficial
Bifidobacterium infantis M-63Reduced Bile Acid SynthesisBeneficial
Bifidobacterium infantis M-63Reduced Hepatic CholesterolBeneficial
Bifidobacterium infantis M-63Reduced Hepatic InflammationBeneficial
Bifidobacterium infantis M-63Reduced Liver TriglyceridesBeneficial
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