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
  • 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
  • 2012-03-06. The cellular and signaling networks linking the immune system and metabolism in disease in NATURE MEDICINE
  • 2017-03-27. Mechanisms for the anti-obesity actions of bofutsushosan in high-fat diet-fed obese mice in CHINESE 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
  • 2019-07-01. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study in NATURE MEDICINE
  • 2006-12-13. Inflammation and metabolic disorders in NATURE
  • 2016-11-28. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice in NATURE MEDICINE
  • 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/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.10.1038/nature05414", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023893418", 
              "https://doi.org/10.1038/nature05414"
            ], 
            "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/nature25979", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1101559358", 
              "https://doi.org/10.1038/nature25979"
            ], 
            "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/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.10.1186/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/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.10.1007/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/nature05485", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042166283", 
              "https://doi.org/10.1038/nature05485"
            ], 
            "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.10.1038/nm.4236", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011574767", 
              "https://doi.org/10.1038/nm.4236"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s13340-017-0339-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1092336351", 
              "https://doi.org/10.1007/s13340-017-0339-6"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "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.10.1038/nm.2627", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023695852", 
              "https://doi.org/10.1038/nm.2627"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00125-013-2885-1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049185943", 
              "https://doi.org/10.1007/s00125-013-2885-1"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "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\u2013induced 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.7534271", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.7535335", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.6835323", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.6834201", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.7537034", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.6822030", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.9337581", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.7545334", 
            "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", 
          "claudin-1", 
          "endotoxin levels", 
          "obesity", 
          "herbal medicine", 
          "cecal contents", 
          "significant decrease", 
          "mice", 
          "fecal samples", 
          "muciniphila", 
          "microbiota", 
          "metabolism", 
          "medicine", 
          "constipation", 
          "endotoxemia", 
          "dysbiosis", 
          "inflammation", 
          "expression", 
          "colon", 
          "intolerance", 
          "Kampo", 
          "treatment", 
          "protein", 
          "Asian countries", 
          "assays", 
          "group", 
          "function", 
          "donors", 
          "sequence analysis", 
          "target", 
          "rRNA sequence analysis", 
          "levels", 
          "decrease", 
          "increase", 
          "effect", 
          "resistance", 
          "changes", 
          "attenuation", 
          "samples", 
          "relative abundance", 
          "data", 
          "permeability", 
          "countries", 
          "analysis", 
          "Herein", 
          "insights", 
          "Verrucomicrobia", 
          "content", 
          "interaction", 
          "abundance", 
          "blooms"
        ], 
        "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": "2022-05-10T10:27", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20220509/entities/gbq_results/article/article_838.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.

    384 TRIPLES      22 PREDICATES      130 URIs      105 LITERALS      21 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/s41598-020-62506-w schema:about N0c22294c70f141769422b74d8ca29d2a
    2 N2cfc3dc58b4a4d9bab386a7557ff09c8
    3 N441b7382d3fa43b38388eb4b25434210
    4 N524f2cebd3c34006b9a276d95fcb7948
    5 N5625321bbea2496680c8316d284407c8
    6 N58906b70d54b45b4aa6107516f7bd01c
    7 N7ad1a2f4178143b2aa611e8ff381904d
    8 N7e589f94a90b4647a95d573d10794b5f
    9 N8e685d46273b4c8aad676270cdec62db
    10 Nafe4803ee17c49e987644bb600402727
    11 Nb63d27f5e1b3402989374abde95e381f
    12 Nce9be43152c4427cb0cc89e09c0e1f22
    13 Nd1bf15ef11c048c392a99b3be4859510
    14 Ne0641c05394b4186abef2cb8f555363f
    15 anzsrc-for:11
    16 anzsrc-for:1103
    17 schema:author N32374361c59e48738f15220b01160f98
    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 N782ffda0c88c48d7b040d546a2381609
    42 N96e128255ff14e9498548c23df836236
    43 sg:journal.1045337
    44 schema:keywords Akkermansia muciniphila
    45 Asian countries
    46 Bofutsushosan
    47 Herein
    48 Japanese herbal medicine
    49 Kampo
    50 Verrucomicrobia
    51 abundance
    52 analysis
    53 antibiotic treatment
    54 assays
    55 attenuation
    56 barrier function
    57 blooms
    58 cecal contents
    59 changes
    60 claudin-1
    61 colon
    62 constipation
    63 content
    64 countries
    65 data
    66 decrease
    67 diet-fed mice
    68 diet-induced inflammation
    69 diet-induced obesity
    70 donors
    71 dysbiosis
    72 effect
    73 endotoxemia
    74 endotoxin levels
    75 expression
    76 fecal samples
    77 function
    78 glucose intolerance
    79 glucose metabolism
    80 group
    81 gut barrier function
    82 gut microbiota
    83 gut permeability
    84 herbal medicine
    85 high-fat diet-fed mice
    86 increase
    87 inflammation
    88 insights
    89 insulin resistance
    90 interaction
    91 intestinal barrier function
    92 intolerance
    93 levels
    94 lipopolysaccharide-binding protein
    95 medicine
    96 metabolic effects
    97 metabolic endotoxemia
    98 metabolism
    99 mice
    100 microbiota
    101 muciniphila
    102 new pharmacological targets
    103 obesity
    104 permeability
    105 pharmacological targets
    106 plasma endotoxin levels
    107 protein
    108 rRNA sequence analysis
    109 relative abundance
    110 resistance
    111 samples
    112 sequence analysis
    113 significant decrease
    114 target
    115 treatment
    116 treatment groups
    117 schema:name Bofutsushosan improves gut barrier function with a bloom of Akkermansia muciniphila and improves glucose metabolism in mice with diet-induced obesity
    118 schema:pagination 5544
    119 schema:productId Nb0b9626b6bb24811a5baa7e71da509d5
    120 Nc8dceca547e448778e2795d9e92bcb1f
    121 Nd431654e2d074cbdb1f4e7b1d5b882d2
    122 schema:sameAs https://app.dimensions.ai/details/publication/pub.1125897054
    123 https://doi.org/10.1038/s41598-020-62506-w
    124 schema:sdDatePublished 2022-05-10T10:27
    125 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    126 schema:sdPublisher Nc4506c96c594411abd366e3cc229a222
    127 schema:url https://doi.org/10.1038/s41598-020-62506-w
    128 sgo:license sg:explorer/license/
    129 sgo:sdDataset articles
    130 rdf:type schema:ScholarlyArticle
    131 N0c22294c70f141769422b74d8ca29d2a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    132 schema:name Sequence Analysis, DNA
    133 rdf:type schema:DefinedTerm
    134 N0cc2643056214f50a7391e2c67986982 rdf:first sg:person.01067673130.15
    135 rdf:rest N8acc5ea0250e444c844371375e6f9598
    136 N161997ba92334b0093eee6ecbc51688c rdf:first sg:person.0657226337.59
    137 rdf:rest N41445b69218f460da90de7589aa54603
    138 N1cd716a65b6b4b0293ede94a1c664756 rdf:first sg:person.01205554101.93
    139 rdf:rest N933a570eb1124bc990a1572b248e8d9f
    140 N2cfc3dc58b4a4d9bab386a7557ff09c8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    141 schema:name Male
    142 rdf:type schema:DefinedTerm
    143 N32374361c59e48738f15220b01160f98 rdf:first sg:person.01071255514.74
    144 rdf:rest Nf23f97be72d14104b48a642f6684ef12
    145 N367d2f32517b4fb195519803d61dfa26 rdf:first sg:person.01162017500.81
    146 rdf:rest Na70bc602712c45e2915a0443d6810057
    147 N41445b69218f460da90de7589aa54603 rdf:first sg:person.01262122516.01
    148 rdf:rest N367d2f32517b4fb195519803d61dfa26
    149 N441b7382d3fa43b38388eb4b25434210 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    150 schema:name Endotoxins
    151 rdf:type schema:DefinedTerm
    152 N47d47ca24faf4f4aa197ceacff1675c0 rdf:first sg:person.015207640272.32
    153 rdf:rest N0cc2643056214f50a7391e2c67986982
    154 N524f2cebd3c34006b9a276d95fcb7948 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    155 schema:name Gastrointestinal Microbiome
    156 rdf:type schema:DefinedTerm
    157 N5625321bbea2496680c8316d284407c8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    158 schema:name Mice
    159 rdf:type schema:DefinedTerm
    160 N58906b70d54b45b4aa6107516f7bd01c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    161 schema:name Blood Glucose
    162 rdf:type schema:DefinedTerm
    163 N6f7e69d89df14e0e89d3e12277800a9e rdf:first sg:person.013140732623.66
    164 rdf:rest Ndac980ec08964e1ab0294b438753f5d8
    165 N782ffda0c88c48d7b040d546a2381609 schema:volumeNumber 10
    166 rdf:type schema:PublicationVolume
    167 N7ad1a2f4178143b2aa611e8ff381904d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    168 schema:name Diet, High-Fat
    169 rdf:type schema:DefinedTerm
    170 N7e589f94a90b4647a95d573d10794b5f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    171 schema:name Akkermansia
    172 rdf:type schema:DefinedTerm
    173 N8acc5ea0250e444c844371375e6f9598 rdf:first sg:person.01100423277.59
    174 rdf:rest rdf:nil
    175 N8e685d46273b4c8aad676270cdec62db schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    176 schema:name Feces
    177 rdf:type schema:DefinedTerm
    178 N933a570eb1124bc990a1572b248e8d9f rdf:first sg:person.0702152471.95
    179 rdf:rest N6f7e69d89df14e0e89d3e12277800a9e
    180 N96e128255ff14e9498548c23df836236 schema:issueNumber 1
    181 rdf:type schema:PublicationIssue
    182 Na70bc602712c45e2915a0443d6810057 rdf:first sg:person.010762216075.77
    183 rdf:rest N1cd716a65b6b4b0293ede94a1c664756
    184 Naf494df0df5f43a58f1e2c3c4386bb31 rdf:first sg:person.0725155054.47
    185 rdf:rest N161997ba92334b0093eee6ecbc51688c
    186 Nafe4803ee17c49e987644bb600402727 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    187 schema:name Obesity
    188 rdf:type schema:DefinedTerm
    189 Nb0b9626b6bb24811a5baa7e71da509d5 schema:name pubmed_id
    190 schema:value 32218475
    191 rdf:type schema:PropertyValue
    192 Nb63d27f5e1b3402989374abde95e381f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    193 schema:name RNA, Ribosomal, 16S
    194 rdf:type schema:DefinedTerm
    195 Nc4506c96c594411abd366e3cc229a222 schema:name Springer Nature - SN SciGraph project
    196 rdf:type schema:Organization
    197 Nc8dceca547e448778e2795d9e92bcb1f schema:name dimensions_id
    198 schema:value pub.1125897054
    199 rdf:type schema:PropertyValue
    200 Nce9be43152c4427cb0cc89e09c0e1f22 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    201 schema:name Drugs, Chinese Herbal
    202 rdf:type schema:DefinedTerm
    203 Nd1bf15ef11c048c392a99b3be4859510 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    204 schema:name Animals
    205 rdf:type schema:DefinedTerm
    206 Nd431654e2d074cbdb1f4e7b1d5b882d2 schema:name doi
    207 schema:value 10.1038/s41598-020-62506-w
    208 rdf:type schema:PropertyValue
    209 Ndac980ec08964e1ab0294b438753f5d8 rdf:first sg:person.01150225633.65
    210 rdf:rest N47d47ca24faf4f4aa197ceacff1675c0
    211 Ne0641c05394b4186abef2cb8f555363f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    212 schema:name Permeability
    213 rdf:type schema:DefinedTerm
    214 Nf23f97be72d14104b48a642f6684ef12 rdf:first sg:person.0650536723.46
    215 rdf:rest Naf494df0df5f43a58f1e2c3c4386bb31
    216 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    217 schema:name Medical and Health Sciences
    218 rdf:type schema:DefinedTerm
    219 anzsrc-for:1103 schema:inDefinedTermSet anzsrc-for:
    220 schema:name Clinical Sciences
    221 rdf:type schema:DefinedTerm
    222 sg:grant.6822030 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-020-62506-w
    223 rdf:type schema:MonetaryGrant
    224 sg:grant.6834201 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-020-62506-w
    225 rdf:type schema:MonetaryGrant
    226 sg:grant.6835323 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-020-62506-w
    227 rdf:type schema:MonetaryGrant
    228 sg:grant.7534271 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-020-62506-w
    229 rdf:type schema:MonetaryGrant
    230 sg:grant.7535335 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-020-62506-w
    231 rdf:type schema:MonetaryGrant
    232 sg:grant.7537034 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-020-62506-w
    233 rdf:type schema:MonetaryGrant
    234 sg:grant.7545334 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-020-62506-w
    235 rdf:type schema:MonetaryGrant
    236 sg:grant.9337581 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-020-62506-w
    237 rdf:type schema:MonetaryGrant
    238 sg:journal.1045337 schema:issn 2045-2322
    239 schema:name Scientific Reports
    240 schema:publisher Springer Nature
    241 rdf:type schema:Periodical
    242 sg:person.01067673130.15 schema:affiliation grid-institutes:grid.267346.2
    243 schema:familyName Nakagawa
    244 schema:givenName Takashi
    245 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01067673130.15
    246 rdf:type schema:Person
    247 sg:person.01071255514.74 schema:affiliation grid-institutes:grid.267346.2
    248 schema:familyName Fujisaka
    249 schema:givenName Shiho
    250 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01071255514.74
    251 rdf:type schema:Person
    252 sg:person.010762216075.77 schema:affiliation grid-institutes:grid.267346.2
    253 schema:familyName Watanabe
    254 schema:givenName Shiro
    255 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010762216075.77
    256 rdf:type schema:Person
    257 sg:person.01100423277.59 schema:affiliation grid-institutes:grid.267346.2
    258 schema:familyName Tobe
    259 schema:givenName Kazuyuki
    260 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01100423277.59
    261 rdf:type schema:Person
    262 sg:person.01150225633.65 schema:affiliation grid-institutes:grid.412803.c
    263 schema:familyName Nagai
    264 schema:givenName Yoshinori
    265 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01150225633.65
    266 rdf:type schema:Person
    267 sg:person.01162017500.81 schema:affiliation grid-institutes:grid.412803.c
    268 schema:familyName Furusawa
    269 schema:givenName Yukihiro
    270 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01162017500.81
    271 rdf:type schema:Person
    272 sg:person.01205554101.93 schema:affiliation grid-institutes:grid.267346.2
    273 schema:familyName Yamamoto
    274 schema:givenName Seiji
    275 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01205554101.93
    276 rdf:type schema:Person
    277 sg:person.01262122516.01 schema:affiliation grid-institutes:grid.452851.f
    278 schema:familyName Okabe
    279 schema:givenName Keisuke
    280 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01262122516.01
    281 rdf:type schema:Person
    282 sg:person.013140732623.66 schema:affiliation grid-institutes:grid.267346.2
    283 schema:familyName Watanabe
    284 schema:givenName Yoshiyuki
    285 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013140732623.66
    286 rdf:type schema:Person
    287 sg:person.015207640272.32 schema:affiliation grid-institutes:grid.267346.2
    288 schema:familyName Yagi
    289 schema:givenName Kunimasa
    290 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015207640272.32
    291 rdf:type schema:Person
    292 sg:person.0650536723.46 schema:affiliation grid-institutes:grid.255137.7
    293 schema:familyName Usui
    294 schema:givenName Isao
    295 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0650536723.46
    296 rdf:type schema:Person
    297 sg:person.0657226337.59 schema:affiliation grid-institutes:grid.267346.2
    298 schema:familyName Igarashi
    299 schema:givenName Yoshiko
    300 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0657226337.59
    301 rdf:type schema:Person
    302 sg:person.0702152471.95 schema:affiliation grid-institutes:grid.267346.2
    303 schema:familyName Sasahara
    304 schema:givenName Masakiyo
    305 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0702152471.95
    306 rdf:type schema:Person
    307 sg:person.0725155054.47 schema:affiliation grid-institutes:grid.267346.2
    308 schema:familyName Nawaz
    309 schema:givenName Allah
    310 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0725155054.47
    311 rdf:type schema:Person
    312 sg:pub.10.1007/s00125-012-2648-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046544147
    313 https://doi.org/10.1007/s00125-012-2648-4
    314 rdf:type schema:CreativeWork
    315 sg:pub.10.1007/s00125-013-2885-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049185943
    316 https://doi.org/10.1007/s00125-013-2885-1
    317 rdf:type schema:CreativeWork
    318 sg:pub.10.1007/s00535-013-0852-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044179037
    319 https://doi.org/10.1007/s00535-013-0852-8
    320 rdf:type schema:CreativeWork
    321 sg:pub.10.1007/s13340-015-0213-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006207216
    322 https://doi.org/10.1007/s13340-015-0213-3
    323 rdf:type schema:CreativeWork
    324 sg:pub.10.1007/s13340-017-0339-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1092336351
    325 https://doi.org/10.1007/s13340-017-0339-6
    326 rdf:type schema:CreativeWork
    327 sg:pub.10.1038/nature05414 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023893418
    328 https://doi.org/10.1038/nature05414
    329 rdf:type schema:CreativeWork
    330 sg:pub.10.1038/nature05485 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042166283
    331 https://doi.org/10.1038/nature05485
    332 rdf:type schema:CreativeWork
    333 sg:pub.10.1038/nature12721 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021135023
    334 https://doi.org/10.1038/nature12721
    335 rdf:type schema:CreativeWork
    336 sg:pub.10.1038/nature25979 schema:sameAs https://app.dimensions.ai/details/publication/pub.1101559358
    337 https://doi.org/10.1038/nature25979
    338 rdf:type schema:CreativeWork
    339 sg:pub.10.1038/nm.2627 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023695852
    340 https://doi.org/10.1038/nm.2627
    341 rdf:type schema:CreativeWork
    342 sg:pub.10.1038/nm.4236 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011574767
    343 https://doi.org/10.1038/nm.4236
    344 rdf:type schema:CreativeWork
    345 sg:pub.10.1038/nm.4345 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085459595
    346 https://doi.org/10.1038/nm.4345
    347 rdf:type schema:CreativeWork
    348 sg:pub.10.1038/nmicrobiol.2016.93 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023953929
    349 https://doi.org/10.1038/nmicrobiol.2016.93
    350 rdf:type schema:CreativeWork
    351 sg:pub.10.1038/nrendo.2014.60 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026639555
    352 https://doi.org/10.1038/nrendo.2014.60
    353 rdf:type schema:CreativeWork
    354 sg:pub.10.1038/nri2710 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033947690
    355 https://doi.org/10.1038/nri2710
    356 rdf:type schema:CreativeWork
    357 sg:pub.10.1038/s41591-019-0495-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1117655252
    358 https://doi.org/10.1038/s41591-019-0495-2
    359 rdf:type schema:CreativeWork
    360 sg:pub.10.1186/s13020-017-0129-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1084251804
    361 https://doi.org/10.1186/s13020-017-0129-x
    362 rdf:type schema:CreativeWork
    363 grid-institutes:grid.255137.7 schema:alternateName Department of Endocrinology and Metabolism, Dokkyo Medical University, Tochigi, Japan
    364 schema:name Department of Endocrinology and Metabolism, Dokkyo Medical University, Tochigi, Japan
    365 First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan
    366 rdf:type schema:Organization
    367 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
    368 Department of Pathology, University of Toyama, Toyama, Japan
    369 Division of Nutritional Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama, Japan
    370 First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan
    371 schema:name Department of Metabolism and Nutrition, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan
    372 Department of Pathology, University of Toyama, Toyama, Japan
    373 Division of Nutritional Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama, Japan
    374 First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan
    375 rdf:type schema:Organization
    376 grid-institutes:grid.412803.c schema:alternateName Department of Liberal Arts and Sciences, Faculty of Engineering, Toyama Prefectural University, Toyama, Japan
    377 Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, Toyama, Japan
    378 schema:name Department of Liberal Arts and Sciences, Faculty of Engineering, Toyama Prefectural University, Toyama, Japan
    379 Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, Toyama, Japan
    380 rdf:type schema:Organization
    381 grid-institutes:grid.452851.f schema:alternateName Department of community Medical Support, Toyama University Hospital, Toyama, Japan
    382 schema:name Department of community Medical Support, Toyama University Hospital, Toyama, Japan
    383 First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan
    384 rdf:type schema:Organization
     




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


    ...