Pharmacologic inhibition of glycolysis prevents the development of lupus by altering the gut microbiome in mice
Summary: Gut dysbiosis has been associated with lupus pathogenesis, and fecal microbiota transfers (FMT) from lupus-prone mice shown to induce autoimmune activation into healthy mice. The immune cells of lupus patients exhibit an increased glucose metabolism and treatments with 2-deoxy-D-glucose (2D...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-07-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223011999 |
| _version_ | 1797774532837113856 |
|---|---|
| author | Ahmed S. Elshikha Yong Ge Josephine Brown Nathalie Kanda Mojgan Zadeh Georges Abboud Seung-Chul Choi Gregg Silverman Timothy J. Garrett William L. Clapp Mansour Mohamadzadeh Laurence Morel |
| author_facet | Ahmed S. Elshikha Yong Ge Josephine Brown Nathalie Kanda Mojgan Zadeh Georges Abboud Seung-Chul Choi Gregg Silverman Timothy J. Garrett William L. Clapp Mansour Mohamadzadeh Laurence Morel |
| author_sort | Ahmed S. Elshikha |
| collection | DOAJ |
| description | Summary: Gut dysbiosis has been associated with lupus pathogenesis, and fecal microbiota transfers (FMT) from lupus-prone mice shown to induce autoimmune activation into healthy mice. The immune cells of lupus patients exhibit an increased glucose metabolism and treatments with 2-deoxy-D-glucose (2DG), a glycolysis inhibitor, are therapeutic in lupus-prone mice. Here, we showed in two models of lupus with different etiologies that 2DG altered the composition of the fecal microbiome and associated metabolites. In both models, FMT from 2DG-treated mice protected lupus-prone mice of the same strain from the development of glomerulonephritis, reduced autoantibody production as well as the activation of CD4+ T cells and myeloid cells as compared to FMT from control mice. Thus, we demonstrated that the protective effect of glucose inhibition in lupus is transferable through the gut microbiota, directly linking alterations in immunometabolism to gut dysbiosis in the hosts. |
| first_indexed | 2024-03-12T22:22:28Z |
| format | Article |
| id | doaj.art-229a7a042b954b65b4b97ba2cac53849 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T22:22:28Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-229a7a042b954b65b4b97ba2cac538492023-07-23T04:55:37ZengElsevieriScience2589-00422023-07-01267107122Pharmacologic inhibition of glycolysis prevents the development of lupus by altering the gut microbiome in miceAhmed S. Elshikha0Yong Ge1Josephine Brown2Nathalie Kanda3Mojgan Zadeh4Georges Abboud5Seung-Chul Choi6Gregg Silverman7Timothy J. Garrett8William L. Clapp9Mansour Mohamadzadeh10Laurence Morel11Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA; The Laboratory of B Cell Immunobiology and the Division of Rheumatology, NYU School of Medicine, New York, NY 10016, USADepartment of Microbiology, Immunology, and Molecular Genetics, University of Texas Health, San Antonio, TX 78229, USA; The Laboratory of B Cell Immunobiology and the Division of Rheumatology, NYU School of Medicine, New York, NY 10016, USADepartment of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Microbiology, Immunology, and Molecular Genetics, University of Texas Health, San Antonio, TX 78229, USADepartment of Microbiology, Immunology, and Molecular Genetics, University of Texas Health, San Antonio, TX 78229, USADepartment of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Microbiology, Immunology, and Molecular Genetics, University of Texas Health, San Antonio, TX 78229, USAThe Laboratory of B Cell Immunobiology and the Division of Rheumatology, NYU School of Medicine, New York, NY 10016, USADepartment of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Microbiology, Immunology, and Molecular Genetics, University of Texas Health, San Antonio, TX 78229, USADepartment of Microbiology, Immunology, and Molecular Genetics, University of Texas Health, San Antonio, TX 78229, USA; Corresponding authorSummary: Gut dysbiosis has been associated with lupus pathogenesis, and fecal microbiota transfers (FMT) from lupus-prone mice shown to induce autoimmune activation into healthy mice. The immune cells of lupus patients exhibit an increased glucose metabolism and treatments with 2-deoxy-D-glucose (2DG), a glycolysis inhibitor, are therapeutic in lupus-prone mice. Here, we showed in two models of lupus with different etiologies that 2DG altered the composition of the fecal microbiome and associated metabolites. In both models, FMT from 2DG-treated mice protected lupus-prone mice of the same strain from the development of glomerulonephritis, reduced autoantibody production as well as the activation of CD4+ T cells and myeloid cells as compared to FMT from control mice. Thus, we demonstrated that the protective effect of glucose inhibition in lupus is transferable through the gut microbiota, directly linking alterations in immunometabolism to gut dysbiosis in the hosts.http://www.sciencedirect.com/science/article/pii/S2589004223011999Pharmaceutical scienceImmune system disorderMicrobiome |
| spellingShingle | Ahmed S. Elshikha Yong Ge Josephine Brown Nathalie Kanda Mojgan Zadeh Georges Abboud Seung-Chul Choi Gregg Silverman Timothy J. Garrett William L. Clapp Mansour Mohamadzadeh Laurence Morel Pharmacologic inhibition of glycolysis prevents the development of lupus by altering the gut microbiome in mice iScience Pharmaceutical science Immune system disorder Microbiome |
| title | Pharmacologic inhibition of glycolysis prevents the development of lupus by altering the gut microbiome in mice |
| title_full | Pharmacologic inhibition of glycolysis prevents the development of lupus by altering the gut microbiome in mice |
| title_fullStr | Pharmacologic inhibition of glycolysis prevents the development of lupus by altering the gut microbiome in mice |
| title_full_unstemmed | Pharmacologic inhibition of glycolysis prevents the development of lupus by altering the gut microbiome in mice |
| title_short | Pharmacologic inhibition of glycolysis prevents the development of lupus by altering the gut microbiome in mice |
| title_sort | pharmacologic inhibition of glycolysis prevents the development of lupus by altering the gut microbiome in mice |
| topic | Pharmaceutical science Immune system disorder Microbiome |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223011999 |
| work_keys_str_mv | AT ahmedselshikha pharmacologicinhibitionofglycolysispreventsthedevelopmentoflupusbyalteringthegutmicrobiomeinmice AT yongge pharmacologicinhibitionofglycolysispreventsthedevelopmentoflupusbyalteringthegutmicrobiomeinmice AT josephinebrown pharmacologicinhibitionofglycolysispreventsthedevelopmentoflupusbyalteringthegutmicrobiomeinmice AT nathaliekanda pharmacologicinhibitionofglycolysispreventsthedevelopmentoflupusbyalteringthegutmicrobiomeinmice AT mojganzadeh pharmacologicinhibitionofglycolysispreventsthedevelopmentoflupusbyalteringthegutmicrobiomeinmice AT georgesabboud pharmacologicinhibitionofglycolysispreventsthedevelopmentoflupusbyalteringthegutmicrobiomeinmice AT seungchulchoi pharmacologicinhibitionofglycolysispreventsthedevelopmentoflupusbyalteringthegutmicrobiomeinmice AT greggsilverman pharmacologicinhibitionofglycolysispreventsthedevelopmentoflupusbyalteringthegutmicrobiomeinmice AT timothyjgarrett pharmacologicinhibitionofglycolysispreventsthedevelopmentoflupusbyalteringthegutmicrobiomeinmice AT williamlclapp pharmacologicinhibitionofglycolysispreventsthedevelopmentoflupusbyalteringthegutmicrobiomeinmice AT mansourmohamadzadeh pharmacologicinhibitionofglycolysispreventsthedevelopmentoflupusbyalteringthegutmicrobiomeinmice AT laurencemorel pharmacologicinhibitionofglycolysispreventsthedevelopmentoflupusbyalteringthegutmicrobiomeinmice |