{"doi":"10.3389/fendo.2021.773340","title":"Bifidobacterium adolescentis Alleviates Liver Steatosis and Steatohepatitis by Increasing Fibroblast Growth Factor 21 Sensitivity","abstract":"<jats:p>The gut microbiota is a newly identified contributor to the development of non-alcoholic fatty liver disease (NAFLD). Previous studies of <jats:italic>Bifidobacterium adolescentis</jats:italic> (<jats:italic>B. adolescentis</jats:italic>), a species of <jats:italic>Bifidobacterium</jats:italic> that is common in the human intestinal tract, have demonstrated that it can alleviate liver steatosis and steatohepatitis. Fibroblast growth factor 21 (FGF21) has long been considered as a biomarker of NAFLD, and recent studies have shown the protective effect of FGF21 analogs on NAFLD. We wondered whether <jats:italic>B. adolescentis</jats:italic> treatment would alleviate NAFLD via the interaction with FGF21. To this end, male C57BL/6J mice on a choline-deficient high-fat diet (CDHFD) were treated with drinking water supplemented with <jats:italic>B. adolescentis</jats:italic> for 8 weeks, followed by the acute administration of recombinant mouse FGF21 protein (rmFGF21) to conduct the FGF21 response test. Consistent with previous studies, <jats:italic>B. adolescentis</jats:italic> supplementation reversed the CDHFD-induced liver steatosis and steatohepatitis. This was evaluated on the NAFLD activity score (NAS), reduced liver enzymes, and lipid accumulation. Further studies demonstrated that <jats:italic>B. adolescentis</jats:italic> supplementation preserved the gut barrier, reduced the gut microbiota-derived lipopolysaccharide (LPS), and inhibited the hepatic TLR4/NF-κB pathway. This was accompanied by the elevated expressions of the receptors of FGF21, fibroblast growth factor receptor 1 (FGFR1) and β-klotho (KLB), in the liver and the decreased expression of FGF21. The results of FGF21 response test showed that <jats:italic>B. adolescentis</jats:italic> supplementation alleviated the CDHFD-induced FGF21 resistance. In vivo experiments suggested that LPS could suppress the expression of FGF21 and KLB in a dose-dependent manner. Collectively, this study showed that <jats:italic>B. adolescentis</jats:italic> supplementation could alleviate NAFLD by increasing FGF21 sensitivity.</jats:p>","journal":"Frontiers in Endocrinology","year":2021,"id":615256,"datarank":0.5983476069846413,"base_score":3.9889840465642745,"endowment":3.9889840465642745,"self_citation_contribution":0.5983476069846413,"citation_network_contribution":0.0,"self_endowment_contribution":0.5983476069846413,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":53,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":14,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":149633,"name":"Dan Liu","orcid":null,"position":1,"is_corresponding":false},{"id":1079454,"name":"Qiongmei Gao","orcid":null,"position":2,"is_corresponding":false},{"id":1585714,"name":"Jiacheng Ni","orcid":null,"position":3,"is_corresponding":false},{"id":734092,"name":"Lingling Qian","orcid":"0000-0001-9282-301X","position":4,"is_corresponding":false},{"id":1585715,"name":"Yueqiong Ni","orcid":null,"position":5,"is_corresponding":false},{"id":1585716,"name":"Qichen Fang","orcid":null,"position":6,"is_corresponding":false},{"id":90150,"name":"Weiping Jia","orcid":"0000-0002-6244-2168","position":7,"is_corresponding":false},{"id":1585718,"name":"Huating Li","orcid":null,"position":8,"is_corresponding":false},{"id":1585712,"name":"Xiaoxue Long","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Bifidobacterium adolescentis Alleviates Liver Steatosis and Steatohepatitis by Increasing Fibroblast Growth Factor 21 Sensitivity","abstract":"<jats:p>The gut microbiota is a newly identified contributor to the development of non-alcoholic fatty liver disease (NAFLD). Previous studies of <jats:italic>Bifidobacterium adolescentis</jats:italic> (<jats:italic>B. adolescentis</jats:italic>), a species of <jats:italic>Bifidobacterium</jats:italic> that is common in the human intestinal tract, have demonstrated that it can alleviate liver steatosis and steatohepatitis. Fibroblast growth factor 21 (FGF21) has long been considered as a biomarker of NAFLD, and recent studies have shown the protective effect of FGF21 analogs on NAFLD. We wondered whether <jats:italic>B. adolescentis</jats:italic> treatment would alleviate NAFLD via the interaction with FGF21. To this end, male C57BL/6J mice on a choline-deficient high-fat diet (CDHFD) were treated with drinking water supplemented with <jats:italic>B. adolescentis</jats:italic> for 8 weeks, followed by the acute administration of recombinant mouse FGF21 protein (rmFGF21) to conduct the FGF21 response test. Consistent with previous studies, <jats:italic>B. adolescentis</jats:italic> supplementation reversed the CDHFD-induced liver steatosis and steatohepatitis. This was evaluated on the NAFLD activity score (NAS), reduced liver enzymes, and lipid accumulation. Further studies demonstrated that <jats:italic>B. adolescentis</jats:italic> supplementation preserved the gut barrier, reduced the gut microbiota-derived lipopolysaccharide (LPS), and inhibited the hepatic TLR4/NF-κB pathway. This was accompanied by the elevated expressions of the receptors of FGF21, fibroblast growth factor receptor 1 (FGFR1) and β-klotho (KLB), in the liver and the decreased expression of FGF21. The results of FGF21 response test showed that <jats:italic>B. adolescentis</jats:italic> supplementation alleviated the CDHFD-induced FGF21 resistance. In vivo experiments suggested that LPS could suppress the expression of FGF21 and KLB in a dose-dependent manner. Collectively, this study showed that <jats:italic>B. adolescentis</jats:italic> supplementation could alleviate NAFLD by increasing FGF21 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