A two-cohort study on the association between the gut microbiota and bone density, microarchitecture, and strength
The gut microbiome affects the inflammatory environment through effects on T-cells, which influence the production of immune mediators and inflammatory cytokines that stimulate osteoclastogenesis and bone loss in mice. However, there are few large human studies of the gut microbiome and skeletal hea...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-09-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1237727/full |
| _version_ | 1827808921834749952 |
|---|---|
| author | Paul C. Okoro Eric S. Orwoll Curtis Huttenhower Curtis Huttenhower Curtis Huttenhower Curtis Huttenhower Xochitl Morgan Thomas M. Kuntz Lauren J. McIver Alyssa B. Dufour Alyssa B. Dufour Mary L. Bouxsein Mary L. Bouxsein Lisa Langsetmo Lisa Langsetmo Samaneh Farsijani Samaneh Farsijani Deborah M. Kado Deborah M. Kado Roberto Pacifici Shivani Sahni Shivani Sahni Douglas P. Kiel Douglas P. Kiel |
| author_facet | Paul C. Okoro Eric S. Orwoll Curtis Huttenhower Curtis Huttenhower Curtis Huttenhower Curtis Huttenhower Xochitl Morgan Thomas M. Kuntz Lauren J. McIver Alyssa B. Dufour Alyssa B. Dufour Mary L. Bouxsein Mary L. Bouxsein Lisa Langsetmo Lisa Langsetmo Samaneh Farsijani Samaneh Farsijani Deborah M. Kado Deborah M. Kado Roberto Pacifici Shivani Sahni Shivani Sahni Douglas P. Kiel Douglas P. Kiel |
| author_sort | Paul C. Okoro |
| collection | DOAJ |
| description | The gut microbiome affects the inflammatory environment through effects on T-cells, which influence the production of immune mediators and inflammatory cytokines that stimulate osteoclastogenesis and bone loss in mice. However, there are few large human studies of the gut microbiome and skeletal health. We investigated the association between the human gut microbiome and high resolution peripheral quantitative computed tomography (HR-pQCT) scans of the radius and tibia in two large cohorts; Framingham Heart Study (FHS [n=1227, age range: 32 – 89]), and the Osteoporosis in Men Study (MrOS [n=836, age range: 78 – 98]). Stool samples from study participants underwent amplification and sequencing of the V4 hypervariable region of the 16S rRNA gene. The resulting 16S rRNA sequencing data were processed separately for each cohort, with the DADA2 pipeline incorporated in the16S bioBakery workflow. Resulting amplicon sequence variants were assigned taxonomies using the SILVA reference database. Controlling for multiple covariates, we tested for associations between microbial taxa abundances and HR-pQCT measures using general linear models as implemented in microbiome multivariable association with linear model (MaAslin2). Abundance of 37 microbial genera in FHS, and 4 genera in MrOS, were associated with various skeletal measures (false discovery rate [FDR] ≤ 0.1) including the association of DTU089 with bone measures, which was independently replicated in the two cohorts. A meta-analysis of the taxa-bone associations further revealed (FDR ≤ 0.25) that greater abundances of the genera; Akkermansia and DTU089, were associated with lower radius total vBMD, and tibia cortical vBMD respectively. Conversely, higher abundances of the genera; Lachnospiraceae NK4A136 group, and Faecalibacterium were associated with greater tibia cortical vBMD. We also investigated functional capabilities of microbial taxa by testing for associations between predicted (based on 16S rRNA amplicon sequence data) metabolic pathways abundance and bone phenotypes in each cohort. While there were no concordant functional associations observed in both cohorts, a meta-analysis revealed 8 pathways including the super-pathway of histidine, purine, and pyrimidine biosynthesis, associated with bone measures of the tibia cortical compartment. In conclusion, our findings suggest that there is a link between the gut microbiome and skeletal metabolism. |
| first_indexed | 2024-03-11T22:34:35Z |
| format | Article |
| id | doaj.art-21de9cfc7b5146db86ebd778fa80cd4e |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-11T22:34:35Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-21de9cfc7b5146db86ebd778fa80cd4e2023-09-22T15:32:53ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-09-011410.3389/fendo.2023.12377271237727A two-cohort study on the association between the gut microbiota and bone density, microarchitecture, and strengthPaul C. Okoro0Eric S. Orwoll1Curtis Huttenhower2Curtis Huttenhower3Curtis Huttenhower4Curtis Huttenhower5Xochitl Morgan6Thomas M. Kuntz7Lauren J. McIver8Alyssa B. Dufour9Alyssa B. Dufour10Mary L. Bouxsein11Mary L. Bouxsein12Lisa Langsetmo13Lisa Langsetmo14Samaneh Farsijani15Samaneh Farsijani16Deborah M. Kado17Deborah M. Kado18Roberto Pacifici19Shivani Sahni20Shivani Sahni21Douglas P. Kiel22Douglas P. Kiel23Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, United StatesDepartment of Medicine, Oregon Health & Sciences University, Portland, OR, United StatesHarvard Chan Microbiome in Public Health Center, Harvard T.H. Chan School of Public Health, Boston, MA, United StatesDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United StatesDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, United StatesInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, United StatesDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United StatesDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United StatesDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United StatesHinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, United StatesDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United StatesEndocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesDepartment of Orthopedic Surgery, Harvard Medical School and Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Boston, MA, United States0Center for Care Delivery and Outcomes Research, Minneapolis Veterans Affairs (VA) Health Care System, Minneapolis, MN, United States1Department of Medicine, University of Minnesota, Minneapolis, MN, United States2Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, United States3Center for Aging and Population Health, University of Pittsburgh, Pittsburgh, PA, United States4Department of Medicine, Stanford University, Stanford, CA, United States5Geriatric Research Education and Clinical Center (GRECC), VA Health System, Palo Alto, CA, United States6Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, United StatesHinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, United StatesDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United StatesHinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, United StatesDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United StatesThe gut microbiome affects the inflammatory environment through effects on T-cells, which influence the production of immune mediators and inflammatory cytokines that stimulate osteoclastogenesis and bone loss in mice. However, there are few large human studies of the gut microbiome and skeletal health. We investigated the association between the human gut microbiome and high resolution peripheral quantitative computed tomography (HR-pQCT) scans of the radius and tibia in two large cohorts; Framingham Heart Study (FHS [n=1227, age range: 32 – 89]), and the Osteoporosis in Men Study (MrOS [n=836, age range: 78 – 98]). Stool samples from study participants underwent amplification and sequencing of the V4 hypervariable region of the 16S rRNA gene. The resulting 16S rRNA sequencing data were processed separately for each cohort, with the DADA2 pipeline incorporated in the16S bioBakery workflow. Resulting amplicon sequence variants were assigned taxonomies using the SILVA reference database. Controlling for multiple covariates, we tested for associations between microbial taxa abundances and HR-pQCT measures using general linear models as implemented in microbiome multivariable association with linear model (MaAslin2). Abundance of 37 microbial genera in FHS, and 4 genera in MrOS, were associated with various skeletal measures (false discovery rate [FDR] ≤ 0.1) including the association of DTU089 with bone measures, which was independently replicated in the two cohorts. A meta-analysis of the taxa-bone associations further revealed (FDR ≤ 0.25) that greater abundances of the genera; Akkermansia and DTU089, were associated with lower radius total vBMD, and tibia cortical vBMD respectively. Conversely, higher abundances of the genera; Lachnospiraceae NK4A136 group, and Faecalibacterium were associated with greater tibia cortical vBMD. We also investigated functional capabilities of microbial taxa by testing for associations between predicted (based on 16S rRNA amplicon sequence data) metabolic pathways abundance and bone phenotypes in each cohort. While there were no concordant functional associations observed in both cohorts, a meta-analysis revealed 8 pathways including the super-pathway of histidine, purine, and pyrimidine biosynthesis, associated with bone measures of the tibia cortical compartment. In conclusion, our findings suggest that there is a link between the gut microbiome and skeletal metabolism.https://www.frontiersin.org/articles/10.3389/fendo.2023.1237727/fullgut microbiome16S amplicon sequencingbone Densitybone microarchitecturecohort studyaging |
| spellingShingle | Paul C. Okoro Eric S. Orwoll Curtis Huttenhower Curtis Huttenhower Curtis Huttenhower Curtis Huttenhower Xochitl Morgan Thomas M. Kuntz Lauren J. McIver Alyssa B. Dufour Alyssa B. Dufour Mary L. Bouxsein Mary L. Bouxsein Lisa Langsetmo Lisa Langsetmo Samaneh Farsijani Samaneh Farsijani Deborah M. Kado Deborah M. Kado Roberto Pacifici Shivani Sahni Shivani Sahni Douglas P. Kiel Douglas P. Kiel A two-cohort study on the association between the gut microbiota and bone density, microarchitecture, and strength Frontiers in Endocrinology gut microbiome 16S amplicon sequencing bone Density bone microarchitecture cohort study aging |
| title | A two-cohort study on the association between the gut microbiota and bone density, microarchitecture, and strength |
| title_full | A two-cohort study on the association between the gut microbiota and bone density, microarchitecture, and strength |
| title_fullStr | A two-cohort study on the association between the gut microbiota and bone density, microarchitecture, and strength |
| title_full_unstemmed | A two-cohort study on the association between the gut microbiota and bone density, microarchitecture, and strength |
| title_short | A two-cohort study on the association between the gut microbiota and bone density, microarchitecture, and strength |
| title_sort | two cohort study on the association between the gut microbiota and bone density microarchitecture and strength |
| topic | gut microbiome 16S amplicon sequencing bone Density bone microarchitecture cohort study aging |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1237727/full |
| work_keys_str_mv | AT paulcokoro atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT ericsorwoll atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT curtishuttenhower atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT curtishuttenhower atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT curtishuttenhower atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT curtishuttenhower atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT xochitlmorgan atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT thomasmkuntz atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT laurenjmciver atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT alyssabdufour atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT alyssabdufour atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT marylbouxsein atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT marylbouxsein atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT lisalangsetmo atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT lisalangsetmo atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT samanehfarsijani atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT samanehfarsijani atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT deborahmkado atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT deborahmkado atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT robertopacifici atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT shivanisahni atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT shivanisahni atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT douglaspkiel atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT douglaspkiel atwocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT paulcokoro twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT ericsorwoll twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT curtishuttenhower twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT curtishuttenhower twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT curtishuttenhower twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT curtishuttenhower twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT xochitlmorgan twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT thomasmkuntz twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT laurenjmciver twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT alyssabdufour twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT alyssabdufour twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT marylbouxsein twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT marylbouxsein twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT lisalangsetmo twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT lisalangsetmo twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT samanehfarsijani twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT samanehfarsijani twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT deborahmkado twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT deborahmkado twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT robertopacifici twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT shivanisahni twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT shivanisahni twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT douglaspkiel twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength AT douglaspkiel twocohortstudyontheassociationbetweenthegutmicrobiotaandbonedensitymicroarchitectureandstrength |