The Gut Microbiota Regulates Endocrine Vitamin D Metabolism through Fibroblast Growth Factor 23
To determine the effect of the microbiota on vitamin D metabolism, serum 25-hydroxyvitamin D(25D), 24,25-dihydroxyvitamin D (24,25D), and 1,25-dihydroxyvitamin D (1,25D) were measured in germ-free (GF) mice before and after conventionalization (CN). GF mice had low levels of 25D, 24,25D, and 1,25D a...
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| Format: | Article |
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Frontiers Media S.A.
2018-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00408/full |
| _version_ | 1818981702132826112 |
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| author | Stephanie A. Bora Stephanie A. Bora Mary J. Kennett Philip B. Smith Philip B. Smith Andrew D. Patterson Andrew D. Patterson Andrew D. Patterson Margherita T. Cantorna Margherita T. Cantorna |
| author_facet | Stephanie A. Bora Stephanie A. Bora Mary J. Kennett Philip B. Smith Philip B. Smith Andrew D. Patterson Andrew D. Patterson Andrew D. Patterson Margherita T. Cantorna Margherita T. Cantorna |
| author_sort | Stephanie A. Bora |
| collection | DOAJ |
| description | To determine the effect of the microbiota on vitamin D metabolism, serum 25-hydroxyvitamin D(25D), 24,25-dihydroxyvitamin D (24,25D), and 1,25-dihydroxyvitamin D (1,25D) were measured in germ-free (GF) mice before and after conventionalization (CN). GF mice had low levels of 25D, 24,25D, and 1,25D and were hypocalcemic. CN of the GF mice with microbiota, for 2 weeks recovered 25D, 24,25D, and 1,25D levels. Females had more 25D and 24,25D than males both as GF mice and after CN. Introducing a limited number of commensals (eight commensals) increased 25D and 24,25D to the same extent as CN. Monocolonization with the enteric pathogen Citrobacter rodentium increased 25D and 24,25D, but the values only increased after 4 weeks of C. rodentium colonization when inflammation resolved. Fibroblast growth factor (FGF) 23 was extremely high in GF mice. CN resulted in an increase in TNF-α expression in the colon 2 days after CN that coincided with a reduction in FGF23 by 3 days that eventually normalized 25D, 24,25D, 1,25D at 1-week post-CN and reinstated calcium homeostasis. Neutralization of FGF23 in GF mice raised 1,25D, without CN, demonstrating that the high FGF23 levels were responsible for the low calcium and 1,25D in GF mice. The microbiota induce inflammation in the GF mice that inhibits FGF23 to eventually reinstate homeostasis that includes increased 25D, 24,25D, and 1,25D levels. The microbiota through FGF23 regulates vitamin D metabolism. |
| first_indexed | 2024-12-20T17:35:31Z |
| format | Article |
| id | doaj.art-426ec199566d44f09228b37d410131ad |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T17:35:31Z |
| publishDate | 2018-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-426ec199566d44f09228b37d410131ad2022-12-21T19:31:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-03-01910.3389/fimmu.2018.00408315814The Gut Microbiota Regulates Endocrine Vitamin D Metabolism through Fibroblast Growth Factor 23Stephanie A. Bora0Stephanie A. Bora1Mary J. Kennett2Philip B. Smith3Philip B. Smith4Andrew D. Patterson5Andrew D. Patterson6Andrew D. Patterson7Margherita T. Cantorna8Margherita T. Cantorna9Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, United StatesThe Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA, United StatesDepartment of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, United StatesThe Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA, United StatesEberly College of Science, The Pennsylvania State University, University Park, PA, United StatesDepartment of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, United StatesThe Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA, United StatesEberly College of Science, The Pennsylvania State University, University Park, PA, United StatesDepartment of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, United StatesThe Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA, United StatesTo determine the effect of the microbiota on vitamin D metabolism, serum 25-hydroxyvitamin D(25D), 24,25-dihydroxyvitamin D (24,25D), and 1,25-dihydroxyvitamin D (1,25D) were measured in germ-free (GF) mice before and after conventionalization (CN). GF mice had low levels of 25D, 24,25D, and 1,25D and were hypocalcemic. CN of the GF mice with microbiota, for 2 weeks recovered 25D, 24,25D, and 1,25D levels. Females had more 25D and 24,25D than males both as GF mice and after CN. Introducing a limited number of commensals (eight commensals) increased 25D and 24,25D to the same extent as CN. Monocolonization with the enteric pathogen Citrobacter rodentium increased 25D and 24,25D, but the values only increased after 4 weeks of C. rodentium colonization when inflammation resolved. Fibroblast growth factor (FGF) 23 was extremely high in GF mice. CN resulted in an increase in TNF-α expression in the colon 2 days after CN that coincided with a reduction in FGF23 by 3 days that eventually normalized 25D, 24,25D, 1,25D at 1-week post-CN and reinstated calcium homeostasis. Neutralization of FGF23 in GF mice raised 1,25D, without CN, demonstrating that the high FGF23 levels were responsible for the low calcium and 1,25D in GF mice. The microbiota induce inflammation in the GF mice that inhibits FGF23 to eventually reinstate homeostasis that includes increased 25D, 24,25D, and 1,25D levels. The microbiota through FGF23 regulates vitamin D metabolism.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00408/fullmicrobiotafibroblast growth factor 23vitamin Dinflammationtumor necrosis factor-α |
| spellingShingle | Stephanie A. Bora Stephanie A. Bora Mary J. Kennett Philip B. Smith Philip B. Smith Andrew D. Patterson Andrew D. Patterson Andrew D. Patterson Margherita T. Cantorna Margherita T. Cantorna The Gut Microbiota Regulates Endocrine Vitamin D Metabolism through Fibroblast Growth Factor 23 Frontiers in Immunology microbiota fibroblast growth factor 23 vitamin D inflammation tumor necrosis factor-α |
| title | The Gut Microbiota Regulates Endocrine Vitamin D Metabolism through Fibroblast Growth Factor 23 |
| title_full | The Gut Microbiota Regulates Endocrine Vitamin D Metabolism through Fibroblast Growth Factor 23 |
| title_fullStr | The Gut Microbiota Regulates Endocrine Vitamin D Metabolism through Fibroblast Growth Factor 23 |
| title_full_unstemmed | The Gut Microbiota Regulates Endocrine Vitamin D Metabolism through Fibroblast Growth Factor 23 |
| title_short | The Gut Microbiota Regulates Endocrine Vitamin D Metabolism through Fibroblast Growth Factor 23 |
| title_sort | gut microbiota regulates endocrine vitamin d metabolism through fibroblast growth factor 23 |
| topic | microbiota fibroblast growth factor 23 vitamin D inflammation tumor necrosis factor-α |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00408/full |
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