Bofutsushosan improves gut barrier function with a bloom of Akkermansia muciniphila and improves glucose metabolism in mice with diet-induced obesity View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-03-26

AUTHORS

Shiho Fujisaka, Isao Usui, Allah Nawaz, Yoshiko Igarashi, Keisuke Okabe, Yukihiro Furusawa, Shiro Watanabe, Seiji Yamamoto, Masakiyo Sasahara, Yoshiyuki Watanabe, Yoshinori Nagai, Kunimasa Yagi, Takashi Nakagawa, Kazuyuki Tobe

ABSTRACT

Obesity and insulin resistance are associated with dysbiosis of the gut microbiota and impaired intestinal barrier function. Herein, we report that Bofutsushosan (BFT), a Japanese herbal medicine, Kampo, which has been clinically used for constipation in Asian countries, ameliorates glucose metabolism in mice with diet-induced obesity. A 16S rRNA sequence analysis of fecal samples showed that BFT dramatically increased the relative abundance of Verrucomicrobia, which was mainly associated with a bloom of Akkermansia muciniphila (AKK). BFT decreased the gut permeability as assessed by FITC-dextran gavage assay, associated with increased expression of tight-junction related protein, claudin-1, in the colon. The BFT treatment group also showed significant decreases of the plasma endotoxin level and expression of the hepatic lipopolysaccharide-binding protein. Antibiotic treatment abrogated the metabolic effects of BFT. Moreover, many of these changes could be reproduced when the cecal contents of BFT-treated donors were transferred to antibiotic-pretreated high fat diet-fed mice. These data demonstrate that BFT modifies the gut microbiota with an increase in AKK, which may contribute to improving gut barrier function and preventing metabolic endotoxemia, leading to attenuation of diet-induced inflammation and glucose intolerance. Understanding the interaction between a medicine and the gut microbiota may provide insights into new pharmacological targets to improve glucose metabolism. More... »

PAGES

5544

References to SciGraph publications

  • 2010-03. Immune adaptations that maintain homeostasis with the intestinal microbiota in NATURE REVIEWS IMMUNOLOGY
  • 2013-11-13. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells in NATURE
  • 2006-12. An obesity-associated gut microbiome with increased capacity for energy harvest in NATURE
  • 2013-06-26. Bofutsushosan, a Japanese herbal (Kampo) medicine, attenuates progression of nonalcoholic steatohepatitis in mice in JOURNAL OF GASTROENTEROLOGY
  • 2012-07-25. Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice in DIABETOLOGIA
  • 2017-03-27. Mechanisms for the anti-obesity actions of bofutsushosan in high-fat diet-fed obese mice in CHINESE MEDICINE
  • 2014-05-13. Beyond intestinal soap—bile acids in metabolic control in NATURE REVIEWS ENDOCRINOLOGY
  • 2013-03-15. Adipose tissue hypoxia induces inflammatory M1 polarity of macrophages in an HIF-1α-dependent and HIF-1α-independent manner in obese mice in DIABETOLOGIA
  • 2016-06-27. Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut in NATURE MICROBIOLOGY
  • 2015-05-29. Deletion of SIRT1 in myeloid cells impairs glucose metabolism with enhancing inflammatory response to adipose tissue hypoxia in DIABETOLOGY INTERNATIONAL
  • 2019-07-01. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study in NATURE MEDICINE
  • 2012-03-06. The cellular and signaling networks linking the immune system and metabolism in disease in NATURE MEDICINE
  • 2017-10-20. Sarcopenia in elderly patients with type 2 diabetes mellitus: prevalence and related clinical factors in DIABETOLOGY INTERNATIONAL
  • 2018-03-19. Extensive impact of non-antibiotic drugs on human gut bacteria in NATURE
  • 2017-05-22. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug in NATURE MEDICINE
  • 2006-12-13. Inflammation and metabolic disorders in NATURE
  • <error retrieving object. in <ERROR RETRIEVING OBJECT
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-020-62506-w

    DOI

    http://dx.doi.org/10.1038/s41598-020-62506-w

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1125897054

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/32218475


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1103", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Clinical Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Akkermansia", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Animals", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Blood Glucose", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Diet, High-Fat", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Drugs, Chinese Herbal", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Endotoxins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Feces", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Gastrointestinal Microbiome", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Male", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Obesity", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Permeability", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "RNA, Ribosomal, 16S", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Sequence Analysis, DNA", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan", 
              "id": "http://www.grid.ac/institutes/grid.267346.2", 
              "name": [
                "First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Fujisaka", 
            "givenName": "Shiho", 
            "id": "sg:person.01071255514.74", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01071255514.74"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Endocrinology and Metabolism, Dokkyo Medical University, Tochigi, Japan", 
              "id": "http://www.grid.ac/institutes/grid.255137.7", 
              "name": [
                "First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan", 
                "Department of Endocrinology and Metabolism, Dokkyo Medical University, Tochigi, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Usui", 
            "givenName": "Isao", 
            "id": "sg:person.0650536723.46", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0650536723.46"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Metabolism and Nutrition, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan", 
              "id": "http://www.grid.ac/institutes/grid.267346.2", 
              "name": [
                "First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan", 
                "Department of Metabolism and Nutrition, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Nawaz", 
            "givenName": "Allah", 
            "id": "sg:person.0725155054.47", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0725155054.47"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan", 
              "id": "http://www.grid.ac/institutes/grid.267346.2", 
              "name": [
                "First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Igarashi", 
            "givenName": "Yoshiko", 
            "id": "sg:person.0657226337.59", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0657226337.59"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of community Medical Support, Toyama University Hospital, Toyama, Japan", 
              "id": "http://www.grid.ac/institutes/grid.452851.f", 
              "name": [
                "First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan", 
                "Department of community Medical Support, Toyama University Hospital, Toyama, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Okabe", 
            "givenName": "Keisuke", 
            "id": "sg:person.01262122516.01", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01262122516.01"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Liberal Arts and Sciences, Faculty of Engineering, Toyama Prefectural University, Toyama, Japan", 
              "id": "http://www.grid.ac/institutes/grid.412803.c", 
              "name": [
                "Department of Liberal Arts and Sciences, Faculty of Engineering, Toyama Prefectural University, Toyama, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Furusawa", 
            "givenName": "Yukihiro", 
            "id": "sg:person.01162017500.81", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01162017500.81"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Division of Nutritional Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama, Japan", 
              "id": "http://www.grid.ac/institutes/grid.267346.2", 
              "name": [
                "Division of Nutritional Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Watanabe", 
            "givenName": "Shiro", 
            "id": "sg:person.010762216075.77", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010762216075.77"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Pathology, University of Toyama, Toyama, Japan", 
              "id": "http://www.grid.ac/institutes/grid.267346.2", 
              "name": [
                "Department of Pathology, University of Toyama, Toyama, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Yamamoto", 
            "givenName": "Seiji", 
            "id": "sg:person.01205554101.93", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01205554101.93"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Pathology, University of Toyama, Toyama, Japan", 
              "id": "http://www.grid.ac/institutes/grid.267346.2", 
              "name": [
                "Department of Pathology, University of Toyama, Toyama, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Sasahara", 
            "givenName": "Masakiyo", 
            "id": "sg:person.0702152471.95", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0702152471.95"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan", 
              "id": "http://www.grid.ac/institutes/grid.267346.2", 
              "name": [
                "First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Watanabe", 
            "givenName": "Yoshiyuki", 
            "id": "sg:person.013140732623.66", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013140732623.66"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, Toyama, Japan", 
              "id": "http://www.grid.ac/institutes/grid.412803.c", 
              "name": [
                "Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, Toyama, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Nagai", 
            "givenName": "Yoshinori", 
            "id": "sg:person.01150225633.65", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01150225633.65"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan", 
              "id": "http://www.grid.ac/institutes/grid.267346.2", 
              "name": [
                "First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Yagi", 
            "givenName": "Kunimasa", 
            "id": "sg:person.015207640272.32", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015207640272.32"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Metabolism and Nutrition, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan", 
              "id": "http://www.grid.ac/institutes/grid.267346.2", 
              "name": [
                "Department of Metabolism and Nutrition, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Nakagawa", 
            "givenName": "Takashi", 
            "id": "sg:person.01067673130.15", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01067673130.15"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan", 
              "id": "http://www.grid.ac/institutes/grid.267346.2", 
              "name": [
                "First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Tobe", 
            "givenName": "Kazuyuki", 
            "id": "sg:person.01100423277.59", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01100423277.59"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/nature12721", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021135023", 
              "https://doi.org/10.1038/nature12721"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13020-017-0129-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1084251804", 
              "https://doi.org/10.1186/s13020-017-0129-x"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature05485", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042166283", 
              "https://doi.org/10.1038/nature05485"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s13340-015-0213-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006207216", 
              "https://doi.org/10.1007/s13340-015-0213-3"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm.4236", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011574767", 
              "https://doi.org/10.1038/nm.4236"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature25979", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1101559358", 
              "https://doi.org/10.1038/nature25979"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00125-013-2885-1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049185943", 
              "https://doi.org/10.1007/s00125-013-2885-1"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature05414", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023893418", 
              "https://doi.org/10.1038/nature05414"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm.2627", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023695852", 
              "https://doi.org/10.1038/nm.2627"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nmicrobiol.2016.93", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023953929", 
              "https://doi.org/10.1038/nmicrobiol.2016.93"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrendo.2014.60", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026639555", 
              "https://doi.org/10.1038/nrendo.2014.60"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00125-012-2648-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046544147", 
              "https://doi.org/10.1007/s00125-012-2648-4"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nri2710", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033947690", 
              "https://doi.org/10.1038/nri2710"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00535-013-0852-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044179037", 
              "https://doi.org/10.1007/s00535-013-0852-8"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm.4345", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1085459595", 
              "https://doi.org/10.1038/nm.4345"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41591-019-0495-2", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1117655252", 
              "https://doi.org/10.1038/s41591-019-0495-2"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s13340-017-0339-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1092336351", 
              "https://doi.org/10.1007/s13340-017-0339-6"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2020-03-26", 
        "datePublishedReg": "2020-03-26", 
        "description": "Obesity and insulin resistance are associated with dysbiosis of the gut microbiota and impaired intestinal barrier function. Herein, we report that Bofutsushosan (BFT), a Japanese herbal medicine, Kampo, which has been clinically used for constipation in Asian countries, ameliorates glucose metabolism in mice with diet-induced obesity. A 16S rRNA sequence analysis of fecal samples showed that BFT dramatically increased the relative abundance of Verrucomicrobia, which was mainly associated with a bloom of Akkermansia muciniphila (AKK). BFT decreased the gut permeability as assessed by FITC-dextran gavage assay, associated with increased expression of tight-junction related protein, claudin-1, in the colon. The BFT treatment group also showed significant decreases of the plasma endotoxin level and expression of the hepatic lipopolysaccharide-binding protein. Antibiotic treatment abrogated the metabolic effects of BFT. Moreover, many of these changes could be reproduced when the cecal contents of BFT-treated donors were transferred to antibiotic-pretreated high fat diet-fed mice. These data demonstrate that BFT modifies the gut microbiota with an increase in AKK, which may contribute to improving gut barrier function and preventing metabolic endotoxemia, leading to attenuation of diet-induced inflammation and glucose intolerance. Understanding the interaction between a medicine and the gut microbiota may provide insights into new pharmacological targets to improve glucose metabolism.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/s41598-020-62506-w", 
        "inLanguage": "en", 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.7545334", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.6835323", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.6834201", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1045337", 
            "issn": [
              "2045-2322"
            ], 
            "name": "Scientific Reports", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "10"
          }
        ], 
        "keywords": [
          "gut barrier function", 
          "diet-induced obesity", 
          "Akkermansia muciniphila", 
          "glucose metabolism", 
          "gut microbiota", 
          "barrier function", 
          "high-fat diet-fed mice", 
          "diet-induced inflammation", 
          "Japanese herbal medicine", 
          "plasma endotoxin levels", 
          "intestinal barrier function", 
          "diet-fed mice", 
          "new pharmacological targets", 
          "lipopolysaccharide-binding protein", 
          "gut permeability", 
          "metabolic endotoxemia", 
          "glucose intolerance", 
          "insulin resistance", 
          "antibiotic treatment", 
          "Bofutsushosan", 
          "metabolic effects", 
          "treatment groups", 
          "pharmacological targets", 
          "endotoxin levels", 
          "claudin-1", 
          "obesity", 
          "herbal medicine", 
          "cecal contents", 
          "significant decrease", 
          "mice", 
          "fecal samples", 
          "muciniphila", 
          "microbiota", 
          "metabolism", 
          "medicine", 
          "constipation", 
          "endotoxemia", 
          "dysbiosis", 
          "inflammation", 
          "expression", 
          "colon", 
          "intolerance", 
          "Kampo", 
          "treatment", 
          "Asian countries", 
          "protein", 
          "assays", 
          "group", 
          "function", 
          "donors", 
          "sequence analysis", 
          "target", 
          "decrease", 
          "levels", 
          "rRNA sequence analysis", 
          "increase", 
          "effect", 
          "resistance", 
          "changes", 
          "attenuation", 
          "samples", 
          "data", 
          "permeability", 
          "relative abundance", 
          "Herein", 
          "countries", 
          "analysis", 
          "insights", 
          "content", 
          "interaction", 
          "Verrucomicrobia", 
          "abundance", 
          "blooms", 
          "FITC-dextran gavage assay", 
          "gavage assay", 
          "BFT treatment group", 
          "hepatic lipopolysaccharide-binding protein", 
          "fat diet-fed mice"
        ], 
        "name": "Bofutsushosan improves gut barrier function with a bloom of Akkermansia muciniphila and improves glucose metabolism in mice with diet-induced obesity", 
        "pagination": "5544", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1125897054"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/s41598-020-62506-w"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "32218475"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/s41598-020-62506-w", 
          "https://app.dimensions.ai/details/publication/pub.1125897054"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-01-01T18:53", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20220101/entities/gbq_results/article/article_847.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/s41598-020-62506-w"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41598-020-62506-w'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41598-020-62506-w'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41598-020-62506-w'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41598-020-62506-w'


     

    This table displays all metadata directly associated to this object as RDF triples.

    379 TRIPLES      22 PREDICATES      135 URIs      110 LITERALS      21 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/s41598-020-62506-w schema:about N11cae63110b4465a9824022ccf616104
    2 N377367f740ee4288b714bc32f7c6a433
    3 N550502561e1a4b0c8a4df6e430f82b3e
    4 N5f9ce8dfc7f5413dac521ed3beb4520d
    5 N61d41bf4fdd24cbbbefe19ec6fee28e6
    6 N6a6e471965db4140908a53593c6d01da
    7 Na716d9af1d864d70b1c539d30b8b5795
    8 Nb6368837d00849a29d5edfe6dd0be7a7
    9 Nd044556eacc84fab8c7895580d7a551a
    10 Nd068536b02ce44568b55680c2a740532
    11 Nd2500161b3db4a23be68edd887223b37
    12 Nda7e7146975246f782ec4a0da14b3dce
    13 Ne7999026a4984e94b4c508d1a9dd0b79
    14 Nf708e1b448394c2f8686474d7f153770
    15 anzsrc-for:11
    16 anzsrc-for:1103
    17 schema:author N8068954693334b589bbc44cd5b3333b3
    18 schema:citation sg:pub.10.1007/s00125-012-2648-4
    19 sg:pub.10.1007/s00125-013-2885-1
    20 sg:pub.10.1007/s00535-013-0852-8
    21 sg:pub.10.1007/s13340-015-0213-3
    22 sg:pub.10.1007/s13340-017-0339-6
    23 sg:pub.10.1038/nature05414
    24 sg:pub.10.1038/nature05485
    25 sg:pub.10.1038/nature12721
    26 sg:pub.10.1038/nature25979
    27 sg:pub.10.1038/nm.2627
    28 sg:pub.10.1038/nm.4236
    29 sg:pub.10.1038/nm.4345
    30 sg:pub.10.1038/nmicrobiol.2016.93
    31 sg:pub.10.1038/nrendo.2014.60
    32 sg:pub.10.1038/nri2710
    33 sg:pub.10.1038/s41591-019-0495-2
    34 sg:pub.10.1186/s13020-017-0129-x
    35 schema:datePublished 2020-03-26
    36 schema:datePublishedReg 2020-03-26
    37 schema:description Obesity and insulin resistance are associated with dysbiosis of the gut microbiota and impaired intestinal barrier function. Herein, we report that Bofutsushosan (BFT), a Japanese herbal medicine, Kampo, which has been clinically used for constipation in Asian countries, ameliorates glucose metabolism in mice with diet-induced obesity. A 16S rRNA sequence analysis of fecal samples showed that BFT dramatically increased the relative abundance of Verrucomicrobia, which was mainly associated with a bloom of Akkermansia muciniphila (AKK). BFT decreased the gut permeability as assessed by FITC-dextran gavage assay, associated with increased expression of tight-junction related protein, claudin-1, in the colon. The BFT treatment group also showed significant decreases of the plasma endotoxin level and expression of the hepatic lipopolysaccharide-binding protein. Antibiotic treatment abrogated the metabolic effects of BFT. Moreover, many of these changes could be reproduced when the cecal contents of BFT-treated donors were transferred to antibiotic-pretreated high fat diet-fed mice. These data demonstrate that BFT modifies the gut microbiota with an increase in AKK, which may contribute to improving gut barrier function and preventing metabolic endotoxemia, leading to attenuation of diet-induced inflammation and glucose intolerance. Understanding the interaction between a medicine and the gut microbiota may provide insights into new pharmacological targets to improve glucose metabolism.
    38 schema:genre article
    39 schema:inLanguage en
    40 schema:isAccessibleForFree true
    41 schema:isPartOf Nd21d5ddc558e4f42b1d6af01eb47340b
    42 Nd2fa02fda2844efa81f1ee163286cd97
    43 sg:journal.1045337
    44 schema:keywords Akkermansia muciniphila
    45 Asian countries
    46 BFT treatment group
    47 Bofutsushosan
    48 FITC-dextran gavage assay
    49 Herein
    50 Japanese herbal medicine
    51 Kampo
    52 Verrucomicrobia
    53 abundance
    54 analysis
    55 antibiotic treatment
    56 assays
    57 attenuation
    58 barrier function
    59 blooms
    60 cecal contents
    61 changes
    62 claudin-1
    63 colon
    64 constipation
    65 content
    66 countries
    67 data
    68 decrease
    69 diet-fed mice
    70 diet-induced inflammation
    71 diet-induced obesity
    72 donors
    73 dysbiosis
    74 effect
    75 endotoxemia
    76 endotoxin levels
    77 expression
    78 fat diet-fed mice
    79 fecal samples
    80 function
    81 gavage assay
    82 glucose intolerance
    83 glucose metabolism
    84 group
    85 gut barrier function
    86 gut microbiota
    87 gut permeability
    88 hepatic lipopolysaccharide-binding protein
    89 herbal medicine
    90 high-fat diet-fed mice
    91 increase
    92 inflammation
    93 insights
    94 insulin resistance
    95 interaction
    96 intestinal barrier function
    97 intolerance
    98 levels
    99 lipopolysaccharide-binding protein
    100 medicine
    101 metabolic effects
    102 metabolic endotoxemia
    103 metabolism
    104 mice
    105 microbiota
    106 muciniphila
    107 new pharmacological targets
    108 obesity
    109 permeability
    110 pharmacological targets
    111 plasma endotoxin levels
    112 protein
    113 rRNA sequence analysis
    114 relative abundance
    115 resistance
    116 samples
    117 sequence analysis
    118 significant decrease
    119 target
    120 treatment
    121 treatment groups
    122 schema:name Bofutsushosan improves gut barrier function with a bloom of Akkermansia muciniphila and improves glucose metabolism in mice with diet-induced obesity
    123 schema:pagination 5544
    124 schema:productId N61fe59021ce349a5bf58f94019473e28
    125 N8ce8355e92bf4710b34156889403221f
    126 Nc85be3fa24904481afc051a705ca019a
    127 schema:sameAs https://app.dimensions.ai/details/publication/pub.1125897054
    128 https://doi.org/10.1038/s41598-020-62506-w
    129 schema:sdDatePublished 2022-01-01T18:53
    130 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    131 schema:sdPublisher N811bec554810400ca341b3eecf1d6a01
    132 schema:url https://doi.org/10.1038/s41598-020-62506-w
    133 sgo:license sg:explorer/license/
    134 sgo:sdDataset articles
    135 rdf:type schema:ScholarlyArticle
    136 N11cae63110b4465a9824022ccf616104 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    137 schema:name Obesity
    138 rdf:type schema:DefinedTerm
    139 N1484fa6c5e334e20bfc8fba72b5e9b4b rdf:first sg:person.01100423277.59
    140 rdf:rest rdf:nil
    141 N2404a49d974149319ef0caecfa27e9db rdf:first sg:person.0725155054.47
    142 rdf:rest N416f33a883ed4637a4b3a4fc55626592
    143 N377367f740ee4288b714bc32f7c6a433 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    144 schema:name Mice
    145 rdf:type schema:DefinedTerm
    146 N416f33a883ed4637a4b3a4fc55626592 rdf:first sg:person.0657226337.59
    147 rdf:rest N7c0ef87e2e444d109c420d65d1108727
    148 N550502561e1a4b0c8a4df6e430f82b3e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    149 schema:name Sequence Analysis, DNA
    150 rdf:type schema:DefinedTerm
    151 N59842ceb8dbf4f3cbb16d218e28fcf88 rdf:first sg:person.010762216075.77
    152 rdf:rest Nd194dae8fca6499f9d179f55c9498eae
    153 N5f9ce8dfc7f5413dac521ed3beb4520d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    154 schema:name Permeability
    155 rdf:type schema:DefinedTerm
    156 N61d41bf4fdd24cbbbefe19ec6fee28e6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    157 schema:name Feces
    158 rdf:type schema:DefinedTerm
    159 N61fe59021ce349a5bf58f94019473e28 schema:name dimensions_id
    160 schema:value pub.1125897054
    161 rdf:type schema:PropertyValue
    162 N6375f454a29944dc95f783fa1c8d61d7 rdf:first sg:person.01067673130.15
    163 rdf:rest N1484fa6c5e334e20bfc8fba72b5e9b4b
    164 N6a6e471965db4140908a53593c6d01da schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    165 schema:name Akkermansia
    166 rdf:type schema:DefinedTerm
    167 N7c0ef87e2e444d109c420d65d1108727 rdf:first sg:person.01262122516.01
    168 rdf:rest Nd36e19b344604e1bb0f01fc7567e0bce
    169 N8068954693334b589bbc44cd5b3333b3 rdf:first sg:person.01071255514.74
    170 rdf:rest Naf8042cfc22a47f4b128125952b7080b
    171 N811bec554810400ca341b3eecf1d6a01 schema:name Springer Nature - SN SciGraph project
    172 rdf:type schema:Organization
    173 N872c8e24a623480ebf254f276ac2cfd5 rdf:first sg:person.01150225633.65
    174 rdf:rest Nad2fc0d19980492993cc09c2f2b7afcf
    175 N8ce8355e92bf4710b34156889403221f schema:name doi
    176 schema:value 10.1038/s41598-020-62506-w
    177 rdf:type schema:PropertyValue
    178 Na716d9af1d864d70b1c539d30b8b5795 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    179 schema:name Endotoxins
    180 rdf:type schema:DefinedTerm
    181 Nad2fc0d19980492993cc09c2f2b7afcf rdf:first sg:person.015207640272.32
    182 rdf:rest N6375f454a29944dc95f783fa1c8d61d7
    183 Naf8042cfc22a47f4b128125952b7080b rdf:first sg:person.0650536723.46
    184 rdf:rest N2404a49d974149319ef0caecfa27e9db
    185 Nb6368837d00849a29d5edfe6dd0be7a7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    186 schema:name RNA, Ribosomal, 16S
    187 rdf:type schema:DefinedTerm
    188 Nc85be3fa24904481afc051a705ca019a schema:name pubmed_id
    189 schema:value 32218475
    190 rdf:type schema:PropertyValue
    191 Nd044556eacc84fab8c7895580d7a551a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    192 schema:name Blood Glucose
    193 rdf:type schema:DefinedTerm
    194 Nd04db5b1e5eb46d5b28cc29f8c084a5e rdf:first sg:person.0702152471.95
    195 rdf:rest Nd9cfdfc367a04e67a3913fc5167abe07
    196 Nd068536b02ce44568b55680c2a740532 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    197 schema:name Animals
    198 rdf:type schema:DefinedTerm
    199 Nd194dae8fca6499f9d179f55c9498eae rdf:first sg:person.01205554101.93
    200 rdf:rest Nd04db5b1e5eb46d5b28cc29f8c084a5e
    201 Nd21d5ddc558e4f42b1d6af01eb47340b schema:volumeNumber 10
    202 rdf:type schema:PublicationVolume
    203 Nd2500161b3db4a23be68edd887223b37 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    204 schema:name Gastrointestinal Microbiome
    205 rdf:type schema:DefinedTerm
    206 Nd2fa02fda2844efa81f1ee163286cd97 schema:issueNumber 1
    207 rdf:type schema:PublicationIssue
    208 Nd36e19b344604e1bb0f01fc7567e0bce rdf:first sg:person.01162017500.81
    209 rdf:rest N59842ceb8dbf4f3cbb16d218e28fcf88
    210 Nd9cfdfc367a04e67a3913fc5167abe07 rdf:first sg:person.013140732623.66
    211 rdf:rest N872c8e24a623480ebf254f276ac2cfd5
    212 Nda7e7146975246f782ec4a0da14b3dce schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    213 schema:name Male
    214 rdf:type schema:DefinedTerm
    215 Ne7999026a4984e94b4c508d1a9dd0b79 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    216 schema:name Drugs, Chinese Herbal
    217 rdf:type schema:DefinedTerm
    218 Nf708e1b448394c2f8686474d7f153770 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    219 schema:name Diet, High-Fat
    220 rdf:type schema:DefinedTerm
    221 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    222 schema:name Medical and Health Sciences
    223 rdf:type schema:DefinedTerm
    224 anzsrc-for:1103 schema:inDefinedTermSet anzsrc-for:
    225 schema:name Clinical Sciences
    226 rdf:type schema:DefinedTerm
    227 sg:grant.6834201 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-020-62506-w
    228 rdf:type schema:MonetaryGrant
    229 sg:grant.6835323 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-020-62506-w
    230 rdf:type schema:MonetaryGrant
    231 sg:grant.7545334 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-020-62506-w
    232 rdf:type schema:MonetaryGrant
    233 sg:journal.1045337 schema:issn 2045-2322
    234 schema:name Scientific Reports
    235 schema:publisher Springer Nature
    236 rdf:type schema:Periodical
    237 sg:person.01067673130.15 schema:affiliation grid-institutes:grid.267346.2
    238 schema:familyName Nakagawa
    239 schema:givenName Takashi
    240 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01067673130.15
    241 rdf:type schema:Person
    242 sg:person.01071255514.74 schema:affiliation grid-institutes:grid.267346.2
    243 schema:familyName Fujisaka
    244 schema:givenName Shiho
    245 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01071255514.74
    246 rdf:type schema:Person
    247 sg:person.010762216075.77 schema:affiliation grid-institutes:grid.267346.2
    248 schema:familyName Watanabe
    249 schema:givenName Shiro
    250 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010762216075.77
    251 rdf:type schema:Person
    252 sg:person.01100423277.59 schema:affiliation grid-institutes:grid.267346.2
    253 schema:familyName Tobe
    254 schema:givenName Kazuyuki
    255 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01100423277.59
    256 rdf:type schema:Person
    257 sg:person.01150225633.65 schema:affiliation grid-institutes:grid.412803.c
    258 schema:familyName Nagai
    259 schema:givenName Yoshinori
    260 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01150225633.65
    261 rdf:type schema:Person
    262 sg:person.01162017500.81 schema:affiliation grid-institutes:grid.412803.c
    263 schema:familyName Furusawa
    264 schema:givenName Yukihiro
    265 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01162017500.81
    266 rdf:type schema:Person
    267 sg:person.01205554101.93 schema:affiliation grid-institutes:grid.267346.2
    268 schema:familyName Yamamoto
    269 schema:givenName Seiji
    270 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01205554101.93
    271 rdf:type schema:Person
    272 sg:person.01262122516.01 schema:affiliation grid-institutes:grid.452851.f
    273 schema:familyName Okabe
    274 schema:givenName Keisuke
    275 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01262122516.01
    276 rdf:type schema:Person
    277 sg:person.013140732623.66 schema:affiliation grid-institutes:grid.267346.2
    278 schema:familyName Watanabe
    279 schema:givenName Yoshiyuki
    280 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013140732623.66
    281 rdf:type schema:Person
    282 sg:person.015207640272.32 schema:affiliation grid-institutes:grid.267346.2
    283 schema:familyName Yagi
    284 schema:givenName Kunimasa
    285 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015207640272.32
    286 rdf:type schema:Person
    287 sg:person.0650536723.46 schema:affiliation grid-institutes:grid.255137.7
    288 schema:familyName Usui
    289 schema:givenName Isao
    290 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0650536723.46
    291 rdf:type schema:Person
    292 sg:person.0657226337.59 schema:affiliation grid-institutes:grid.267346.2
    293 schema:familyName Igarashi
    294 schema:givenName Yoshiko
    295 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0657226337.59
    296 rdf:type schema:Person
    297 sg:person.0702152471.95 schema:affiliation grid-institutes:grid.267346.2
    298 schema:familyName Sasahara
    299 schema:givenName Masakiyo
    300 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0702152471.95
    301 rdf:type schema:Person
    302 sg:person.0725155054.47 schema:affiliation grid-institutes:grid.267346.2
    303 schema:familyName Nawaz
    304 schema:givenName Allah
    305 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0725155054.47
    306 rdf:type schema:Person
    307 sg:pub.10.1007/s00125-012-2648-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046544147
    308 https://doi.org/10.1007/s00125-012-2648-4
    309 rdf:type schema:CreativeWork
    310 sg:pub.10.1007/s00125-013-2885-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049185943
    311 https://doi.org/10.1007/s00125-013-2885-1
    312 rdf:type schema:CreativeWork
    313 sg:pub.10.1007/s00535-013-0852-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044179037
    314 https://doi.org/10.1007/s00535-013-0852-8
    315 rdf:type schema:CreativeWork
    316 sg:pub.10.1007/s13340-015-0213-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006207216
    317 https://doi.org/10.1007/s13340-015-0213-3
    318 rdf:type schema:CreativeWork
    319 sg:pub.10.1007/s13340-017-0339-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1092336351
    320 https://doi.org/10.1007/s13340-017-0339-6
    321 rdf:type schema:CreativeWork
    322 sg:pub.10.1038/nature05414 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023893418
    323 https://doi.org/10.1038/nature05414
    324 rdf:type schema:CreativeWork
    325 sg:pub.10.1038/nature05485 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042166283
    326 https://doi.org/10.1038/nature05485
    327 rdf:type schema:CreativeWork
    328 sg:pub.10.1038/nature12721 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021135023
    329 https://doi.org/10.1038/nature12721
    330 rdf:type schema:CreativeWork
    331 sg:pub.10.1038/nature25979 schema:sameAs https://app.dimensions.ai/details/publication/pub.1101559358
    332 https://doi.org/10.1038/nature25979
    333 rdf:type schema:CreativeWork
    334 sg:pub.10.1038/nm.2627 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023695852
    335 https://doi.org/10.1038/nm.2627
    336 rdf:type schema:CreativeWork
    337 sg:pub.10.1038/nm.4236 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011574767
    338 https://doi.org/10.1038/nm.4236
    339 rdf:type schema:CreativeWork
    340 sg:pub.10.1038/nm.4345 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085459595
    341 https://doi.org/10.1038/nm.4345
    342 rdf:type schema:CreativeWork
    343 sg:pub.10.1038/nmicrobiol.2016.93 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023953929
    344 https://doi.org/10.1038/nmicrobiol.2016.93
    345 rdf:type schema:CreativeWork
    346 sg:pub.10.1038/nrendo.2014.60 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026639555
    347 https://doi.org/10.1038/nrendo.2014.60
    348 rdf:type schema:CreativeWork
    349 sg:pub.10.1038/nri2710 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033947690
    350 https://doi.org/10.1038/nri2710
    351 rdf:type schema:CreativeWork
    352 sg:pub.10.1038/s41591-019-0495-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1117655252
    353 https://doi.org/10.1038/s41591-019-0495-2
    354 rdf:type schema:CreativeWork
    355 sg:pub.10.1186/s13020-017-0129-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1084251804
    356 https://doi.org/10.1186/s13020-017-0129-x
    357 rdf:type schema:CreativeWork
    358 grid-institutes:grid.255137.7 schema:alternateName Department of Endocrinology and Metabolism, Dokkyo Medical University, Tochigi, Japan
    359 schema:name Department of Endocrinology and Metabolism, Dokkyo Medical University, Tochigi, Japan
    360 First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan
    361 rdf:type schema:Organization
    362 grid-institutes:grid.267346.2 schema:alternateName Department of Metabolism and Nutrition, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan
    363 Department of Pathology, University of Toyama, Toyama, Japan
    364 Division of Nutritional Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama, Japan
    365 First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan
    366 schema:name Department of Metabolism and Nutrition, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan
    367 Department of Pathology, University of Toyama, Toyama, Japan
    368 Division of Nutritional Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama, Japan
    369 First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan
    370 rdf:type schema:Organization
    371 grid-institutes:grid.412803.c schema:alternateName Department of Liberal Arts and Sciences, Faculty of Engineering, Toyama Prefectural University, Toyama, Japan
    372 Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, Toyama, Japan
    373 schema:name Department of Liberal Arts and Sciences, Faculty of Engineering, Toyama Prefectural University, Toyama, Japan
    374 Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, Toyama, Japan
    375 rdf:type schema:Organization
    376 grid-institutes:grid.452851.f schema:alternateName Department of community Medical Support, Toyama University Hospital, Toyama, Japan
    377 schema:name Department of community Medical Support, Toyama University Hospital, Toyama, Japan
    378 First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan
    379 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...