Gut microbiota composition explains more variance in the host cardiometabolic risk than genetic ancestry

ABSTRACT: Cardiometabolic affections greatly contribute to the global burden of disease. The susceptibility to obesity, cardiovascular disease, and type-2 diabetes, conditions that add to the cardiometabolic syndrome (CMS), was associated with the ancestral genetic composition and gut microbiota. St...

Full description

Autores:
Guzmán Castañeda, Sandra Janeth
Ortega Vega, Esteban Leandro
Rojas Montoya, Winston
Bedoya Berrío, Gabriel de Jesús
de la Cuesta Zuluaga, Jacobo
Velásquez Mejía, Eliana P.
Escobar, Juan
Tipo de recurso:
Article of investigation
Fecha de publicación:
2020
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/41124
Acceso en línea:
https://hdl.handle.net/10495/41124
Palabra clave:
Bacteria
Bacterias
Cardiovascular Diseases
Enfermedades Cardiovasculares
Cohort Studies
Estudios de Cohortes
Cross-Sectional Studies
Estudios Transversales
Gastrointestinal Microbiome
Microbioma Gastrointestinal
Genetic Predisposition to Disease
Predisposición Genética a la Enfermedad
Metagenomics
Metagenómica
RNA, Ribosomal, 16S
ARN Ribosómico 16S
Risk Factors
Factores de Riesgo
https://id.nlm.nih.gov/mesh/D001419
https://id.nlm.nih.gov/mesh/D002318
https://id.nlm.nih.gov/mesh/D015331
https://id.nlm.nih.gov/mesh/D003430
https://id.nlm.nih.gov/mesh/D000069196
https://id.nlm.nih.gov/mesh/D020022
https://id.nlm.nih.gov/mesh/D056186
https://id.nlm.nih.gov/mesh/D012336
https://id.nlm.nih.gov/mesh/D012307
Rights
openAccess
License
http://creativecommons.org/licenses/by/2.5/co/
id UDEA2_32a304812d25e63941a830ef398c0de2
oai_identifier_str oai:bibliotecadigital.udea.edu.co:10495/41124
network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.spa.fl_str_mv Gut microbiota composition explains more variance in the host cardiometabolic risk than genetic ancestry
title Gut microbiota composition explains more variance in the host cardiometabolic risk than genetic ancestry
spellingShingle Gut microbiota composition explains more variance in the host cardiometabolic risk than genetic ancestry
Bacteria
Bacterias
Cardiovascular Diseases
Enfermedades Cardiovasculares
Cohort Studies
Estudios de Cohortes
Cross-Sectional Studies
Estudios Transversales
Gastrointestinal Microbiome
Microbioma Gastrointestinal
Genetic Predisposition to Disease
Predisposición Genética a la Enfermedad
Metagenomics
Metagenómica
RNA, Ribosomal, 16S
ARN Ribosómico 16S
Risk Factors
Factores de Riesgo
https://id.nlm.nih.gov/mesh/D001419
https://id.nlm.nih.gov/mesh/D002318
https://id.nlm.nih.gov/mesh/D015331
https://id.nlm.nih.gov/mesh/D003430
https://id.nlm.nih.gov/mesh/D000069196
https://id.nlm.nih.gov/mesh/D020022
https://id.nlm.nih.gov/mesh/D056186
https://id.nlm.nih.gov/mesh/D012336
https://id.nlm.nih.gov/mesh/D012307
title_short Gut microbiota composition explains more variance in the host cardiometabolic risk than genetic ancestry
title_full Gut microbiota composition explains more variance in the host cardiometabolic risk than genetic ancestry
title_fullStr Gut microbiota composition explains more variance in the host cardiometabolic risk than genetic ancestry
title_full_unstemmed Gut microbiota composition explains more variance in the host cardiometabolic risk than genetic ancestry
title_sort Gut microbiota composition explains more variance in the host cardiometabolic risk than genetic ancestry
dc.creator.fl_str_mv Guzmán Castañeda, Sandra Janeth
Ortega Vega, Esteban Leandro
Rojas Montoya, Winston
Bedoya Berrío, Gabriel de Jesús
de la Cuesta Zuluaga, Jacobo
Velásquez Mejía, Eliana P.
Escobar, Juan
dc.contributor.author.none.fl_str_mv Guzmán Castañeda, Sandra Janeth
Ortega Vega, Esteban Leandro
Rojas Montoya, Winston
Bedoya Berrío, Gabriel de Jesús
de la Cuesta Zuluaga, Jacobo
Velásquez Mejía, Eliana P.
Escobar, Juan
dc.contributor.researchgroup.spa.fl_str_mv Genética Molecular (GENMOL)
dc.subject.decs.none.fl_str_mv Bacteria
Bacterias
Cardiovascular Diseases
Enfermedades Cardiovasculares
Cohort Studies
Estudios de Cohortes
Cross-Sectional Studies
Estudios Transversales
Gastrointestinal Microbiome
Microbioma Gastrointestinal
Genetic Predisposition to Disease
Predisposición Genética a la Enfermedad
Metagenomics
Metagenómica
RNA, Ribosomal, 16S
ARN Ribosómico 16S
Risk Factors
Factores de Riesgo
topic Bacteria
Bacterias
Cardiovascular Diseases
Enfermedades Cardiovasculares
Cohort Studies
Estudios de Cohortes
Cross-Sectional Studies
Estudios Transversales
Gastrointestinal Microbiome
Microbioma Gastrointestinal
Genetic Predisposition to Disease
Predisposición Genética a la Enfermedad
Metagenomics
Metagenómica
RNA, Ribosomal, 16S
ARN Ribosómico 16S
Risk Factors
Factores de Riesgo
https://id.nlm.nih.gov/mesh/D001419
https://id.nlm.nih.gov/mesh/D002318
https://id.nlm.nih.gov/mesh/D015331
https://id.nlm.nih.gov/mesh/D003430
https://id.nlm.nih.gov/mesh/D000069196
https://id.nlm.nih.gov/mesh/D020022
https://id.nlm.nih.gov/mesh/D056186
https://id.nlm.nih.gov/mesh/D012336
https://id.nlm.nih.gov/mesh/D012307
dc.subject.meshuri.none.fl_str_mv https://id.nlm.nih.gov/mesh/D001419
https://id.nlm.nih.gov/mesh/D002318
https://id.nlm.nih.gov/mesh/D015331
https://id.nlm.nih.gov/mesh/D003430
https://id.nlm.nih.gov/mesh/D000069196
https://id.nlm.nih.gov/mesh/D020022
https://id.nlm.nih.gov/mesh/D056186
https://id.nlm.nih.gov/mesh/D012336
https://id.nlm.nih.gov/mesh/D012307
description ABSTRACT: Cardiometabolic affections greatly contribute to the global burden of disease. The susceptibility to obesity, cardiovascular disease, and type-2 diabetes, conditions that add to the cardiometabolic syndrome (CMS), was associated with the ancestral genetic composition and gut microbiota. Studies explicitly testing associations between genetic ancestry and gut microbes are growing. We here examined whether the host genetic ancestry was associated with gut microbiota composition, and distinguished the effects of genetic ancestry and non-genetic factors on human cardiometabolic health. We performed a cross-sectional study with 441 community-dwelling Colombian mestizos from five cities spanning the Andes, Pacific, and Caribbean coasts. We characterized the host genetic ancestry by genotyping 40 ancestry informative markers; characterized gut microbiota through 16S rRNA gene sequencing; assessed diet intake, physical activity, cigarette, and medicament consumption; and measured cardiometabolic outcomes that allowed calculating a CMS risk scale. On average, each individual of our cohort was 67 ± 6% European, 21 ± 5% Native American and 12 ± 5% African. Multivariable-adjusted generalized linear models showed that individuals with higher Native American and African ancestries had increased fasting insulin, body mass index and CMS risk, as assessed by the CMS risk scale. Furthermore, we identified 21 OTUs associated to the host genetic ancestry and 20 to cardiometabolic health. While we highlight novel associations between genetic ancestry and gut microbiota, we found that the effect of intestinal microbes was more likely to explain the variance in CMS risk scale than the contributions of European, Native American and African genetic backgrounds.
publishDate 2020
dc.date.issued.none.fl_str_mv 2020
dc.date.accessioned.none.fl_str_mv 2024-08-12T22:40:40Z
dc.date.available.none.fl_str_mv 2024-08-12T22:40:40Z
dc.type.spa.fl_str_mv Artículo de investigación
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.redcol.spa.fl_str_mv https://purl.org/redcol/resource_type/ART
dc.type.coarversion.spa.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/article
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/publishedVersion
format http://purl.org/coar/resource_type/c_2df8fbb1
status_str publishedVersion
dc.identifier.citation.spa.fl_str_mv Guzmán-Castañeda SJ, Ortega-Vega EL, de la Cuesta-Zuluaga J, Velásquez-Mejía EP, Rojas W, Bedoya G, Escobar JS. Gut microbiota composition explains more variance in the host cardiometabolic risk than genetic ancestry. Gut Microbes. 2020;11(2):191-204. doi: 10.1080/19490976.2019.1634416. Epub 2019 Jul 16.
dc.identifier.issn.none.fl_str_mv 1949-0976
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10495/41124
dc.identifier.doi.none.fl_str_mv 10.1080/19490976.2019.1634416
dc.identifier.eissn.none.fl_str_mv 1949-0984
identifier_str_mv Guzmán-Castañeda SJ, Ortega-Vega EL, de la Cuesta-Zuluaga J, Velásquez-Mejía EP, Rojas W, Bedoya G, Escobar JS. Gut microbiota composition explains more variance in the host cardiometabolic risk than genetic ancestry. Gut Microbes. 2020;11(2):191-204. doi: 10.1080/19490976.2019.1634416. Epub 2019 Jul 16.
1949-0976
10.1080/19490976.2019.1634416
1949-0984
url https://hdl.handle.net/10495/41124
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.ispartofjournalabbrev.spa.fl_str_mv Gut Microbes
dc.relation.citationendpage.spa.fl_str_mv 204
dc.relation.citationissue.spa.fl_str_mv 2
dc.relation.citationstartpage.spa.fl_str_mv 191
dc.relation.citationvolume.spa.fl_str_mv 11
dc.relation.ispartofjournal.spa.fl_str_mv Gut Microbes
dc.rights.uri.*.fl_str_mv http://creativecommons.org/licenses/by/2.5/co/
dc.rights.uri.spa.fl_str_mv https://creativecommons.org/licenses/by-nc/4.0/
dc.rights.accessrights.spa.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.coar.spa.fl_str_mv http://purl.org/coar/access_right/c_abf2
rights_invalid_str_mv http://creativecommons.org/licenses/by/2.5/co/
https://creativecommons.org/licenses/by-nc/4.0/
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.extent.spa.fl_str_mv 14 páginas
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Taylor and Francis
dc.publisher.place.spa.fl_str_mv Filadelfia, Estados Unidos
institution Universidad de Antioquia
bitstream.url.fl_str_mv https://bibliotecadigital.udea.edu.co/bitstreams/94995930-a371-47e4-b9c2-5d4aa34f477b/download
https://bibliotecadigital.udea.edu.co/bitstreams/c17c74ba-112b-49b7-ac4a-b794ecfed2f9/download
https://bibliotecadigital.udea.edu.co/bitstreams/2d4b6baf-3568-4bef-90c0-7434439f4620/download
https://bibliotecadigital.udea.edu.co/bitstreams/5e8427b3-e60c-4ef1-b293-6cd46094aac6/download
https://bibliotecadigital.udea.edu.co/bitstreams/0f45853d-27fd-434d-81cd-b56d21ae764a/download
bitstream.checksum.fl_str_mv 1646d1f6b96dbbbc38035efc9239ac9c
8a4605be74aa9ea9d79846c1fba20a33
8ba9fc41baa939c2de23c0111da0ea5e
999a435a4c9b472ccc4f8402ad0759e2
ab39ef3520d95c37db5520229dbd3ddb
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositorio Institucional de la Universidad de Antioquia
repository.mail.fl_str_mv aplicacionbibliotecadigitalbiblioteca@udea.edu.co
_version_ 1851052226026405888
spelling Guzmán Castañeda, Sandra JanethOrtega Vega, Esteban LeandroRojas Montoya, WinstonBedoya Berrío, Gabriel de Jesúsde la Cuesta Zuluaga, JacoboVelásquez Mejía, Eliana P.Escobar, JuanGenética Molecular (GENMOL)2024-08-12T22:40:40Z2024-08-12T22:40:40Z2020Guzmán-Castañeda SJ, Ortega-Vega EL, de la Cuesta-Zuluaga J, Velásquez-Mejía EP, Rojas W, Bedoya G, Escobar JS. Gut microbiota composition explains more variance in the host cardiometabolic risk than genetic ancestry. Gut Microbes. 2020;11(2):191-204. doi: 10.1080/19490976.2019.1634416. Epub 2019 Jul 16.1949-0976https://hdl.handle.net/10495/4112410.1080/19490976.2019.16344161949-0984ABSTRACT: Cardiometabolic affections greatly contribute to the global burden of disease. The susceptibility to obesity, cardiovascular disease, and type-2 diabetes, conditions that add to the cardiometabolic syndrome (CMS), was associated with the ancestral genetic composition and gut microbiota. Studies explicitly testing associations between genetic ancestry and gut microbes are growing. We here examined whether the host genetic ancestry was associated with gut microbiota composition, and distinguished the effects of genetic ancestry and non-genetic factors on human cardiometabolic health. We performed a cross-sectional study with 441 community-dwelling Colombian mestizos from five cities spanning the Andes, Pacific, and Caribbean coasts. We characterized the host genetic ancestry by genotyping 40 ancestry informative markers; characterized gut microbiota through 16S rRNA gene sequencing; assessed diet intake, physical activity, cigarette, and medicament consumption; and measured cardiometabolic outcomes that allowed calculating a CMS risk scale. On average, each individual of our cohort was 67 ± 6% European, 21 ± 5% Native American and 12 ± 5% African. Multivariable-adjusted generalized linear models showed that individuals with higher Native American and African ancestries had increased fasting insulin, body mass index and CMS risk, as assessed by the CMS risk scale. Furthermore, we identified 21 OTUs associated to the host genetic ancestry and 20 to cardiometabolic health. While we highlight novel associations between genetic ancestry and gut microbiota, we found that the effect of intestinal microbes was more likely to explain the variance in CMS risk scale than the contributions of European, Native American and African genetic backgrounds.Colombia. Ministerio de Ciencia, Tecnología e Innovación - MincienciasUniversidad de AntioquiaGrupo NutresaDinámica IPSEPS SURACOL000672314 páginasapplication/pdfengTaylor and FrancisFiladelfia, Estados Unidoshttp://creativecommons.org/licenses/by/2.5/co/https://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Gut microbiota composition explains more variance in the host cardiometabolic risk than genetic ancestryArtículo de investigaciónhttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARThttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionBacteriaBacteriasCardiovascular DiseasesEnfermedades CardiovascularesCohort StudiesEstudios de CohortesCross-Sectional StudiesEstudios TransversalesGastrointestinal MicrobiomeMicrobioma GastrointestinalGenetic Predisposition to DiseasePredisposición Genética a la EnfermedadMetagenomicsMetagenómicaRNA, Ribosomal, 16SARN Ribosómico 16SRisk FactorsFactores de Riesgohttps://id.nlm.nih.gov/mesh/D001419https://id.nlm.nih.gov/mesh/D002318https://id.nlm.nih.gov/mesh/D015331https://id.nlm.nih.gov/mesh/D003430https://id.nlm.nih.gov/mesh/D000069196https://id.nlm.nih.gov/mesh/D020022https://id.nlm.nih.gov/mesh/D056186https://id.nlm.nih.gov/mesh/D012336https://id.nlm.nih.gov/mesh/D012307Gut Microbes204219111Gut MicrobesEvaluación del efecto de factores genéticos asociados a obesidad sobre la composición de la microbiota intestinal en población adulta colombianaMinciencias 111565741349RoR:03fd5ne08RoR:03bp5hc83PublicationCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8927https://bibliotecadigital.udea.edu.co/bitstreams/94995930-a371-47e4-b9c2-5d4aa34f477b/download1646d1f6b96dbbbc38035efc9239ac9cMD52falseAnonymousREADLICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://bibliotecadigital.udea.edu.co/bitstreams/c17c74ba-112b-49b7-ac4a-b794ecfed2f9/download8a4605be74aa9ea9d79846c1fba20a33MD53falseAnonymousREADORIGINALBedoyaGabriel_2020_Gut_Microbiota_Cardiometabolic.pdfBedoyaGabriel_2020_Gut_Microbiota_Cardiometabolic.pdfArtículo de investigaciónapplication/pdf3174047https://bibliotecadigital.udea.edu.co/bitstreams/2d4b6baf-3568-4bef-90c0-7434439f4620/download8ba9fc41baa939c2de23c0111da0ea5eMD51trueAnonymousREADTEXTBedoyaGabriel_2020_Gut_Microbiota_Cardiometabolic.pdf.txtBedoyaGabriel_2020_Gut_Microbiota_Cardiometabolic.pdf.txtExtracted texttext/plain64689https://bibliotecadigital.udea.edu.co/bitstreams/5e8427b3-e60c-4ef1-b293-6cd46094aac6/download999a435a4c9b472ccc4f8402ad0759e2MD54falseAnonymousREADTHUMBNAILBedoyaGabriel_2020_Gut_Microbiota_Cardiometabolic.pdf.jpgBedoyaGabriel_2020_Gut_Microbiota_Cardiometabolic.pdf.jpgGenerated Thumbnailimage/jpeg10410https://bibliotecadigital.udea.edu.co/bitstreams/0f45853d-27fd-434d-81cd-b56d21ae764a/downloadab39ef3520d95c37db5520229dbd3ddbMD55falseAnonymousREAD10495/41124oai:bibliotecadigital.udea.edu.co:10495/411242025-03-26 18:55:53.546http://creativecommons.org/licenses/by/2.5/co/open.accesshttps://bibliotecadigital.udea.edu.coRepositorio Institucional de la Universidad de Antioquiaaplicacionbibliotecadigitalbiblioteca@udea.edu.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