Journal
MOLECULAR NUTRITION & FOOD RESEARCH
Volume 63, Issue 20, Pages -Publisher
WILEY
DOI: 10.1002/mnfr.201900487
Keywords
bile acids; gut microbiota; gut-liver axis; hepatic metabolism; non-alcoholic fatty liver disease
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Funding
- Instituto de Salud Carlos III [PI17/01089]
- Ministerio de Economia y Competitividad/Fondo Europeo de Desarrollo Regional (FEDER) [BFU2013-48141-R, BFU2017-87960-R]
- Junta de Castilla y Leon/FEDER [LE063U16, GRS1888/A/18]
- Sara Borrell Postdoctoral Contract from the Instituto de Salud Carlos III [CD18/00158]
- Junta de Castilla y Leon - European Social Fund
- Fundacion de Investigacion Sanitaria of Leon
- CIBERehd contracts
- Instituto de Salud Carlos III, Spain
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Scope Gut microbiota contributes to non-alcoholic fatty liver disease (NAFLD) pathogenesis by multiple mechanisms not yet completely understood. Novel differential features between germ-free mice (GFm) transplanted with protective or non-protective cecal microbiota against NAFLD are investigated. Methods and results Gut microbiota composition, plasma, and fecal bile acids (BAs) and liver mRNAs are quantified in GFm recipients from four donor mice differing in NAFLD severity (control diet, high-fat diet [HFD]-responder, HFD-non-responder, and quercetin-supplemented HFD). Transplanted GFm are on control or HFD for 16-weeks. Multivariate analysis shows that GFm colonized with microbiota from HFD-non-responder and quercetin supplemented-HFD donors (protected against NAFLD) clusters together, whereas GFm colonized with microbiota from control and HFD-responder mice (non-protected against NAFLD) establishes another cluster. Protected phenotype is associated with increased gut Desulfovibrio and Oscillospira, reduced gut Bacteroides and Oribacterium, lower primary and higher secondary BAs in plasma and feces, induction of hepatic BA transporters, and repression of hepatic lipogenic and BA synthesis genes. Conclusion Protective gut microbiota associates with increased specific secondary BAs, which likely inhibit lipogenic pathways and enhance bile flow in the liver. This novel cross-talk between gut and liver, via plasma BAs, that promotes protection against NAFLD may have clinical and nutritional relevance.
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