Caracterización de la composición bacteriana fecal en pacientes con enfermedad de Parkinson y controles sanos de Colombia
La enfermedad de Parkinson es un trastorno neurodegenerativo, que se basa principalmente en el deterioro de la sustancia nigra pars compacta del cerebro y que trae como consecuencia la pérdida de células dopaminérgicas. La alteración de diversos sistemas neuronales son los causales de los síntomas m...
- Autores:
-
Arias Rodríguez, Natalia
- Tipo de recurso:
- Trabajo de grado de pregrado
- Fecha de publicación:
- 2021
- Institución:
- Colegio Mayor de Cundinamarca
- Repositorio:
- Repositorio Colegio Mayor de Cundinamarca
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unicolmayor.edu.co:unicolmayor/2834
- Acceso en línea:
- https://repositorio.unicolmayor.edu.co/handle/unicolmayor/2834
- Palabra clave:
- Composición bacteriana
Trastorno neurodegenerativo
Células dopaminérgicas
Enfermedad de Parkinson
Parkinson idiopático
microbiota intestinal
Disbiosis intestinal
Metabolitos bacterianos
Neuroinflamación
Sistema nervioso central
Sistema nervioso entérico
- Rights
- closedAccess
- License
- Derechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2021
| id |
UCOLMAYOR2_8184e4c35cb75497916ba262edaef60b |
|---|---|
| oai_identifier_str |
oai:repositorio.unicolmayor.edu.co:unicolmayor/2834 |
| network_acronym_str |
UCOLMAYOR2 |
| network_name_str |
Repositorio Colegio Mayor de Cundinamarca |
| repository_id_str |
|
| dc.title.spa.fl_str_mv |
Caracterización de la composición bacteriana fecal en pacientes con enfermedad de Parkinson y controles sanos de Colombia |
| title |
Caracterización de la composición bacteriana fecal en pacientes con enfermedad de Parkinson y controles sanos de Colombia |
| spellingShingle |
Caracterización de la composición bacteriana fecal en pacientes con enfermedad de Parkinson y controles sanos de Colombia Composición bacteriana Trastorno neurodegenerativo Células dopaminérgicas Enfermedad de Parkinson Parkinson idiopático microbiota intestinal Disbiosis intestinal Metabolitos bacterianos Neuroinflamación Sistema nervioso central Sistema nervioso entérico |
| title_short |
Caracterización de la composición bacteriana fecal en pacientes con enfermedad de Parkinson y controles sanos de Colombia |
| title_full |
Caracterización de la composición bacteriana fecal en pacientes con enfermedad de Parkinson y controles sanos de Colombia |
| title_fullStr |
Caracterización de la composición bacteriana fecal en pacientes con enfermedad de Parkinson y controles sanos de Colombia |
| title_full_unstemmed |
Caracterización de la composición bacteriana fecal en pacientes con enfermedad de Parkinson y controles sanos de Colombia |
| title_sort |
Caracterización de la composición bacteriana fecal en pacientes con enfermedad de Parkinson y controles sanos de Colombia |
| dc.creator.fl_str_mv |
Arias Rodríguez, Natalia |
| dc.contributor.advisor.none.fl_str_mv |
Hernández Rojas, Edith del Carmen Forero Rodríguez, Lady Johanna |
| dc.contributor.author.none.fl_str_mv |
Arias Rodríguez, Natalia |
| dc.subject.lemb.none.fl_str_mv |
Composición bacteriana Trastorno neurodegenerativo Células dopaminérgicas |
| topic |
Composición bacteriana Trastorno neurodegenerativo Células dopaminérgicas Enfermedad de Parkinson Parkinson idiopático microbiota intestinal Disbiosis intestinal Metabolitos bacterianos Neuroinflamación Sistema nervioso central Sistema nervioso entérico |
| dc.subject.proposal.spa.fl_str_mv |
Enfermedad de Parkinson Parkinson idiopático microbiota intestinal Disbiosis intestinal Metabolitos bacterianos Neuroinflamación Sistema nervioso central Sistema nervioso entérico |
| description |
La enfermedad de Parkinson es un trastorno neurodegenerativo, que se basa principalmente en el deterioro de la sustancia nigra pars compacta del cerebro y que trae como consecuencia la pérdida de células dopaminérgicas. La alteración de diversos sistemas neuronales son los causales de los síntomas motores y no motores de la enfermedad entre los que se encuentra el estreñimiento, presente en cerca del 80% de pacientes con EP, incluso 20 años antes del diagnóstico. Teniendo de base la comunicación bidireccional entre el cerebro y el intestino y los recientes estudios que reportan alterada composición bacteriana en pacientes vs controles sanos, se vio pertinente evaluar la composición bacteriana fecal de 25 pacientes con EP y 25 controles sanos de Colombia, a través de extracción de ADN, secuenciación del gen 16 's rRNA por Illumina y análisis taxonómico - bioinformático en R Studio. Se identificó que, no había diferencias significativas en la riqueza y abundancia en las muestras a través de la diversidad alfa; mientras que la diversidad beta, con la medida Weight UniFrac Bray Curtis, evidencio diferencias entre pacientes y controles, comprobado por la prueba estadística ANOSIM. Adicionalmente, se destaca una disminución en las familias Lactobacillaceae y Streptococcaceae, y un aumento de Lachnospiraceae, Ruminoccocaceae, Verrucomicrobiaceae y Peptostreptococcaceae, esta última es por primera vez descrita como significativa en los casos de Colombia, la cual está implicada en la síntesis de AGCC, degradación de mucina y fibras vegetales, siendo importantes para el mantenimiento de la barrera intestinal y la neuroprotección. |
| publishDate |
2021 |
| dc.date.accessioned.none.fl_str_mv |
2021-09-09T21:22:07Z |
| dc.date.available.none.fl_str_mv |
2021-09-09T21:22:07Z |
| dc.date.issued.none.fl_str_mv |
2021-05-21 |
| dc.type.spa.fl_str_mv |
Trabajo de grado - Pregrado |
| dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_7a1f |
| dc.type.coarversion.spa.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.content.spa.fl_str_mv |
Text |
| dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/bachelorThesis |
| dc.type.redcol.spa.fl_str_mv |
https://purl.org/redcol/resource_type/TP |
| dc.type.version.spa.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| format |
http://purl.org/coar/resource_type/c_7a1f |
| status_str |
publishedVersion |
| dc.identifier.uri.none.fl_str_mv |
https://repositorio.unicolmayor.edu.co/handle/unicolmayor/2834 |
| url |
https://repositorio.unicolmayor.edu.co/handle/unicolmayor/2834 |
| dc.language.iso.spa.fl_str_mv |
spa |
| language |
spa |
| dc.relation.references.spa.fl_str_mv |
Resolución número 8430. [internet] República de Colombia. Bogotá: Ministerio de salud; 1993 [10 de septiembre de 2020]. Recuperado de https://urosario.edu.co/Escuela- Medicina/Investigacion/Documentos-de-inte res/Files/resolucion_008430_1993.pdf. Resolución número 1164. [internet] República de Colombia. Bogotá: Ministerio de salud y Ministerio de ambiente y desarrollo sostenible; 2002 [10 de septiembre de 2020]. Recuperado de http://www.udea.edu.co/wps/wcm/connect/udea/8ef2b54c- c7a3-4d32-8dde- ddf2c0bd9dc9/Resoluci%C3%B3n+1164+de+2002.pdf?MOD= AJPERES. Husebye E. The pathogenesis of gastrointestinal bacterial overgrowth. University Hospital of Oslo. Oslo. Norway, Chemotherapy. [internet] 2005 [cited 16 sept 2020]. vol 51(suppl 1):1–22. Available from doi: 10.1159/000081988. Levy O, Malagelada C & Greene L. Cell death pathways in Parkinson’s disease: proximal triggers, distal effectors, and final steps. Columbia University School of Medicine. New York, NY, USA, review, Springer. [internet] 2009 [cited 16 sept 2020]. vol 14:478–500. Available from doi: 10.1007/s10495-008-0309-3. Hawkes C, Tredici K & Braak H. A timeline for Parkinson’s disease. Deutsche Forschungsgemeinschaft (DFG) and Hilde- Ulrichs Foundation,Germany, Florstadt Staden, review, Elsevier. [internet] 2009 [cited 13 jul 2020]. vol 16, 79–84. Available from doi: 10.1016/j.parkreldis.2009.08.007. Gutierrez J y Singer C- Parkinsonismo: diagnósticos alternativos a la enfermedad idiopática de Parkinson. School of Medicine, Department of Neurology, University of Miami, U.S.A. review, Rev Med Inst Mex Seguro Soc. [internet] 2010 [citado 13 jul 2020]. Vol 48 (3): 279-292. Available from https://www.medigraphic.com/pdfs/imss/im-2010/im103h.pdf. Shulman J, Lager P & Feany M. Parkinson ́s disease: genetics and pathogenesis. University of Alabama, Birmingham. Annual reviews. [internet] 2011 [cited 13 jul 2020]. Vol 6:193–222. Available from doi: 10.1146/annurev-pathol-011110-130242. Elizondo G, Dector M, Martinez H, Martinez L y Esmer M. Genética y la enfermedad de Parkinson: revisiones actualizadas. Departamento de genética de Nuevo México, Elsevier [internet] 2011 [citado 11 de agosto de 2020]. Vol. 13. Issue 51: (96-100), recuperado de: https://www.elsevier.es/en-revista-medicina-universitaria-304- articulo-geneti caenfermedad-parkinson-revision-actualidades- X1665579611240564. Chávez I. Microbiota intestinal en la salud y la enfermedad. Universidad Anáhuac Mayab, Yucatán México. Revista de gastroenterología de México, Elsevier. [internet] 2013 [cited 20 may 2020]. Vol (4):240-248, recuperado de htts://doi.org/10.1016/j.rgmx.2013.04.004. Sonco R. Estudio de la diversidad alfa y beta en tres localidades de un bosque montano en la región de Madidi. La paz – Bolívar. Universidad Mayor de San Andrés. [internet] 2013 [cited 10 de marzo 2021]. Vol 1- 154, recuperado de #search/ljforeror%40unal.edu.co/FMfcgxwKkRPFGjWqddtZZhd WNqgzBnn D?projector=1&messagePartId=0.1. Scheperjans F, Aho V, Pereira P, Koskinen k & Paulin L.Gut Microbiota Are Related to Parkinson’s Disease and Clinical Phenotype. PubMed. [internet] 2014 [cited 23 de may 2019]. Vol: 30(3):350-8, available from: 10.1002/mds.26069. Escobar J, Klotz B, Valdes B E & Agudelo G.M. The gut microbiota of Colombians differs from that of Americans, Europeans and Asians. PubMed [internet] 2014 [ cited el 23 mayo 2019]. Vol: 14;14:311, available from: 10.1186/s12866- 014-0311-6. Keshavarzian A, Green S.J, Engen P.A, Voigt R.M, & Ankur Naqib. Colonic Bacterial Composition in Parkinson’s Disease. PubMed. [internet] 2015 [cited 23 may 2019]. Vol: 30(10):1351- 60, available from: 10.1002/mds.26307. Valenzuela F,Casillas R, Villalpando E y Vargas F. El gen ARNr 16S en el estudio de comunidades microbianas marinas. México. SCielo, [internet] 2015 [cita 20 marzo 2021]. Vol.41 no.4, tomado de: https://doi.org/10.7773/cm.v41i4.2492. Hasegawa S, Goto S, Tsuji H, Okuno T, Asahara T & Nomoto K. Intestinal Dysbiosis and Lowered Serum Lipopolysaccharide- Binding Protein in Parkinson’s Disease. Hertie Institute for Clinical Brain Research and German Center. PLOS. [internet] 2015 [cited 23 may 2020]. Vol 10 (11): e0142164, available from doi: 10.1371 / journal.pone.0142164. Obregon A, Tito R, Metcalf J, Sankaranarayanan K, Clemente J & Ursell L. Subsistence strategies in traditional societies distinguish gut microbiomes. Oklahoma, USA. Nature. [internet] 2015 [cited 10 of march of 2021]. Vol: 6:6505. Retrieved from: doi: 10.1038/ncomms7505. Mardinoglu A, Boren J & Smith U. Confounding Effects of Metformin on the Human Gut Microbiome in Type 2 Diabetes. Stockholm. Cell Press. [internet] 2016 [cited 10 march 2021]. available from: http://dx.doi.org/10.1016/j.cmet.2015.12.012. Unger M, Spiegel J, Dillman K, Grundmann D, Phillippeit H & Burmann J. Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls. Germany. Elsevier. [internet] 2016 [cited 23 may 2020]. 1-7. Available from http://dx.doi.org/10.1016/j.parkreldis.2016.08.019. Patrick P, Etienne C and Stephane H. Understanding Dopaminergic Cell Death Pathways in Parkinson Disease. Neuron. Paris. [internet] 2016 [cited 11/08/20], available from: http://dx.doi.org/10.1016/j.neuron.2016.03.038. Anderson G, Seo M, Berk M, Carvalho A & Maes M. Gut Permeability and Microbiota in Parkinson’s Disease: Role of Depression, Tryptophan Catabolites, Oxidative and Nitrosative Stress and Melatonergic Pathways. UK, London. Review, Bentham Science. [Internet] 2016 [cited 16 sept 2020]. Vol: 22, 6142-6151, available from doi: 10.2174/1381612822666160906161513. Oksanen J. Vegan: ecological diversity, r project. [internet] 2016 [cited 10 of march of 2021]. Available from: https://cran.r- project.org/web/packages/vegan/vignettes/diversity-vegan.pdf. Hopfner F, Künstner A and Müller S. Gut microbiota in Parkinson disease in a northern German cohort. Kiel University, Germany. Elsevier. [internet] 2017 [cited 20 may 2020]. Vol: 41-45. Available from: http://dx.doi.org/10.1016/j.brainres.2017.04.019 0006-8993/ 2017. Callahan B, McMurdie P & Holmes S. Exact sequence variants should replace operational taxonomic units in marker-gene data analysis. USA. The ISME Journa. [internet] 2017 [cited 10 of march of 2021]. Vol: 11, 2639–2643. Available from: https://www.nature.com/articles/ismej2017119.pdf. Klingelhoefer L & Reichmann H. Parkinson’s disease as a multisystem disorder. Department of Neurology. Technical University Dresden, Germany. Springer. [internet] 2017 [cited 20 sept 2020]. Available from: 10.1007/s00702-017-1692-0. Rietdijk C, Perez P, Garssen j, van Weezel R & Kraneveld A. Exploring Braak hypothesis of Parkinson's disease. Netherlands, review, Frontiers in Neurology. [internet] 2017 [cited 20 sep 2020]. Vol: 8: art 37. Available from doi: 10.3389/fneur.2017.00037. Li W, Wu X and Wang T. Structural changes of gut microbiota Parkinson's disease and its correlation with clinical features, Key Laboratory Mental Health.Institute of Psychology. Chinese Academy of Sciences,Beijing. Science China.[internet] 2017 [cited 20 may 2020]. Vol:60 No.11:1223–1233 , Available from: doi: 10.1007/s11427-016-9001-4. Heintz A, Pandey U and Wicke T. The nasal and gut microbiome in Parkinson’s disease and idiopathic rapid eye movement sleep behavior disorder. University of Luxembourg. Esch-sur-Alzette, Luxembourg. Movement Disorders. [internet] 2017 [cited 20 may 2020]. Vol. 33, No. 1, 2018. Available from: DOI: 10.1002/mds.27105. Hill E, Debelius J and Morton J. Parkinson’s disease and PD medications have distinct signatures of the gut microbiome. University of California. San Diego, USA. Mov Disord. [internet] 2017 [cited 20 may 2020]. Vol: 32(5): 739–749. Available from: doi:10.1002/mds.26942. Petrov V, Saltykova I and Zhukova V. Analysis of Gut Microbiota in Patients with Parkinson’s Disease. University, Moscow, Russia. Byulleten’ Eksperimental’noi Biologii i Meditsiny. [internet]. 2017 [cited 20 may 2020]. Vol: 162, No. 12, pp. 700- 703. Available from: doi: 10.1007/s10517-017-3700-7. Gerritsen J, Hornung B, Renckens B, Van S, Martins V & Rijkers G. Genomic and functional analysis of Romboutsia ilealis CRIBT reveals adaptation to the small intestine. The Netherlands, PeerJ, review. [Internet] 2017 [cited 10 march 2021]. Available from: DOI 10.7717/peerj.3698. Marín D, Carmona H, Ibarra M, Gámez M. Enfermedad de Parkinson: fisiopatología, diagnóstico y tratamiento. Rev Univ Ind Santander Salud. [internet] 2018 [cited 11/08/20]. Vol: 50(1): 79-92, recuperado de: doi: 10.18273/revsal.v50n1-2018008. Mulak A. A Controversy on the Role of Short-Chain Fatty Acids in the Pathogenesis of Parkinson’s Disease. Department of Gastroenterology and Hepatology. Wroclaw Medical University, Wroclaw Poland. Movement Disorders. [internet] 2018 [cited 20 may 2020]. Vol. 00, No. 00. available from: DOI: 10.1002/mds.27304. Ma N & Ma X. Dietary Amino Acids and the Gut-Microbiome- Immune Axis: Physiological Metabolism and Therapeutic Prospects. China. Comprehensive, review. [internet] 2018 [cited 10 march 2021]. Vol 18, available from: doi: 10.1111/1541- 4337.12401. Lin A, Zheng W and He Y. Gut microbiota in patients with Parkinson's disease in southern China. Department of Neurology. Zhujiang Hospital, Southern Medical University, Guangzhou, China. Parkinsonism and Related Disorders. [internet] 2018 [cited 20 may 2020]. Vol. 53, 82–88, available from: https://doi.org/10.1016/j.parkreldis.2018.05.007. Fei M and Qin Y. Dysbiosis of gut microbiota and microbial metabolites Parkinson's Disease. Wuxi Medical School, Jiangnan University, Wuxi, China. Elsevier. [Internet] 2018 [cited 20 may 2020]. Vol. 45, 53–61. Available from: https://doi.org/10.1016/j.arr.2018.04.004. Costea P, Hildebrand F, Manimozhiyan A, Bäckhed F, Blaser M & Bushman F. Enterotypes in the landscape of gut microbial community composition. Germany. Review Springer nature. [internet] 2018 [cited 16 sep 2020]. Vol: 3; 8-16. Available from doi: https://doi.org/10.1038/s41564-017-0072-8. Barichella M, Severgnini M, Cilia R, et al. Unraveling gut microbiota in Parkinson’s disease and atypical Parkinsonism, Parkinson Institute, Azienda Socio Sanitaria Territoriale. Milan, Italy. Movement Disorders. [internet] 2018 [cited 20 may 2020]. Available from: doi:10.1002/mds.27581. Liang S, Wu X & Jin F, Gut-Brain Psychology: Rethinking Psychology From the Microbiota–Gut–Brain Axis, University of China. Beijing. Review Frontiers. [internet] 2018 [cited 20 may 2020]. 12: 33. Available from doi: doi: 10.3389/fnint.2018.00033. Fitzgerald E, Murphy S and Martinson H. Alpha-Synuclein Pathology and the Role of the Microbiota in Parkinson’s Disease. USA. Review, Frontiers. [internet] 2019 [cited 9/5/2020]. Available from: https://doi.org/10.3389/fnins.2019.00369. Rusell J, Roesch L, Ördberg M, Ilonen J,Atkinson M & Schatz D. Genetic risk for autoimmunity is associated with distinct changes in the human gut microbiome. USA. Nature. [internet] 2019 [cited 10 march 2021]. Vol: 10:3621. Available from: | https://doi.org/10.1038/s41467-019-11460-x. Rengarajan S, Vivio E, Parkes M, Peterson D, Roberson E & Newberry R. Dynamic immunoglobulin responses to gut bacteria during inflammatory bowel disease. USA, . RENGARAJAN ET AL. [internet] 2019 [cited 10 march 2021]. Vol: 11:3, 405-420. Available from: https://doi.org/10.1080/19490976.2019.1626683. Li C, Cui L and Yang Y. Gut microbiota differs between Parkinson’s disease patients and healthy controls in Northeast China, Department of Neurology and Neuroscience Center, Changchun. China. Front. Mol. Neurosci. [internet] 2019 [cited 20 may 2020]. Available from https://doi.org/10.3389/fnmol.2019.00171. Li F, Wang P, Chen Z, et al. Alteration of the fecal microbiota in North-Eastern Han Chinese population with sporadic Parkinson's disease, Liaoning Province. China. Elsevier [internet] 2019 [cited 20 may 2020]. 707,134297. Available from: https://doi.org/10.1016/j.neulet.2019.134297. Baldini F, Hertel J, Sandt E, et al. Parkinson’s disease- associated alterations of the gut microbiome can invoke disease-relevant metabolic change, Centre for Systems Biomedicine, University of Luxembourg. Luxembourg. bioRxiv [internet] 2019 [cited 20 may 2020]. Available from: http://dx.doi.org/10.1101/691030. Fernandez J y Granados I, Enfermedad de Parkinson: neurodegeneración asociada con el Estrés Oxidativo. Universidad Popular del Cesar, Valledupar. Colombia. Panorama: Cuba y salud. [internet] 2020 [citado 20 mayo 2020]. Vol: ;15(2): 45-52. Available from: http://www.revpanorama.sld.cu/index.php/rpan/article/view/. Oksanen J, Vegan: an introduction to ordination, cran r project. [internet] 2020 [cited 10 march 2021]. Available from: https://cran.r-project.org/web/packages/vegan/vignettes/intro- vegan.pdf. Zhang F, Zhao Q, Fang X, Xu M, Tang J & Zhang Y. Metagenomic analysis of gut microbiota in Parkinson's disease patients from Central China, Hubei University of Medicine. China. Research Square. [internet] 2020 [cited 10 oct 2020]. Available from doi:10.21203/rs.2.21271/v2. Arkesenen D, Weimers P, Marker D ,Johannesen T ,Iversen S & Lilje B. Disease activity measures are related to the faecal gut microbiota in adult patients with ulcerative colitis. USA. Taylor y Francis. [internet] 2020 [cited 20 march 2021]. Available from: https://doi.org/10.1080/00365521.2020.1829031. Kitamono S, Kitamono H, Hein R, Schmidt T & Kamada N. The Bacterial Connection between the Oral Cavity and the Gut Diseases. USA. Journal of Dental Research. [internet] 2020 [cited 20 march 2021]. Vol: 1-9. Available from: DOI: 10.1177/0022034520924633 journal. |
| dc.rights.spa.fl_str_mv |
Derechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2021 |
| dc.rights.uri.spa.fl_str_mv |
https://creativecommons.org/licenses/by-nc-sa/4.0/ |
| dc.rights.accessrights.spa.fl_str_mv |
info:eu-repo/semantics/closedAccess |
| dc.rights.creativecommons.spa.fl_str_mv |
Atribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0) |
| dc.rights.coar.spa.fl_str_mv |
http://purl.org/coar/access_right/c_14cb |
| rights_invalid_str_mv |
Derechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2021 https://creativecommons.org/licenses/by-nc-sa/4.0/ Atribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0) http://purl.org/coar/access_right/c_14cb |
| eu_rights_str_mv |
closedAccess |
| dc.format.extent.spa.fl_str_mv |
160p. |
| dc.format.mimetype.spa.fl_str_mv |
application/pdf |
| dc.publisher.spa.fl_str_mv |
Universidad Colegio Mayor de Cundinamarca |
| dc.publisher.faculty.spa.fl_str_mv |
Facultad de Ciencias de la Salud |
| dc.publisher.place.spa.fl_str_mv |
Bogotá D.C |
| dc.publisher.program.spa.fl_str_mv |
Bacteriología y Laboratorio Clínico |
| institution |
Colegio Mayor de Cundinamarca |
| bitstream.url.fl_str_mv |
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/1/Natalia%20Arias%20Rodr%c3%adguez%20Caracterizaci%c3%b3n%20de%20la%20composici%c3%b3n%20bacteriana%20fecal%20de%20pacientes%20con%20EP%20y%20controles%20sanos%20de%20Colombia%20Natalia%20Arias.pdf https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/2/FORMATO%20DERECHOS%20DE%20AUTOR%20TG%202021%20%20%282%29.pdf https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/3/Formato%20decanatura%203.pdf https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/4/Natalia%20Arias%20Rodr%c3%adguez%20Trabajo%20de%20grado%20Natalia%20Arias.pdf https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/5/license.txt https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/6/Natalia%20Arias%20Rodr%c3%adguez%20Caracterizaci%c3%b3n%20de%20la%20composici%c3%b3n%20bacteriana%20fecal%20de%20pacientes%20con%20EP%20y%20controles%20sanos%20de%20Colombia%20Natalia%20Arias.pdf.txt https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/8/FORMATO%20DERECHOS%20DE%20AUTOR%20TG%202021%20%20%282%29.pdf.txt https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/10/Formato%20decanatura%203.pdf.txt https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/7/Natalia%20Arias%20Rodr%c3%adguez%20Caracterizaci%c3%b3n%20de%20la%20composici%c3%b3n%20bacteriana%20fecal%20de%20pacientes%20con%20EP%20y%20controles%20sanos%20de%20Colombia%20Natalia%20Arias.pdf.jpg https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/9/FORMATO%20DERECHOS%20DE%20AUTOR%20TG%202021%20%20%282%29.pdf.jpg https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/11/Formato%20decanatura%203.pdf.jpg |
| bitstream.checksum.fl_str_mv |
a2a72b602d8ca6e117a52816a73b6250 b583ddaabe2ab727e14295f660aa4ca4 5c9d711032dad99cde9e1ad597973c9b 35d40ab17eeaf81dd8b8276d556da31a 2f9959eaf5b71fae44bbf9ec84150c7a 52722c26a2cd6aba40e43519bce7102f 31a660745e377a2c7c1d4be1f6637b30 68b329da9893e34099c7d8ad5cb9c940 745ef94c2bf699d936c0b468aa75be12 a9a977f10b92c5488e375b9ca97e5d26 125acae089e6ede6cb20d1f11fb40437 |
| bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 |
| repository.name.fl_str_mv |
Biblioteca Digital Unicolmayor |
| repository.mail.fl_str_mv |
repositorio@unicolmayor.edu.co |
| _version_ |
1812210093801865216 |
| spelling |
Hernández Rojas, Edith del Carmen691add7415cca2135c3de6050313997bForero Rodríguez, Lady Johanna228fe1c93075a95cb80c9a79189120bcArias Rodríguez, Natalia2b87d588a494a33d102942ec5ac1489e2021-09-09T21:22:07Z2021-09-09T21:22:07Z2021-05-21https://repositorio.unicolmayor.edu.co/handle/unicolmayor/2834La enfermedad de Parkinson es un trastorno neurodegenerativo, que se basa principalmente en el deterioro de la sustancia nigra pars compacta del cerebro y que trae como consecuencia la pérdida de células dopaminérgicas. La alteración de diversos sistemas neuronales son los causales de los síntomas motores y no motores de la enfermedad entre los que se encuentra el estreñimiento, presente en cerca del 80% de pacientes con EP, incluso 20 años antes del diagnóstico. Teniendo de base la comunicación bidireccional entre el cerebro y el intestino y los recientes estudios que reportan alterada composición bacteriana en pacientes vs controles sanos, se vio pertinente evaluar la composición bacteriana fecal de 25 pacientes con EP y 25 controles sanos de Colombia, a través de extracción de ADN, secuenciación del gen 16 's rRNA por Illumina y análisis taxonómico - bioinformático en R Studio. Se identificó que, no había diferencias significativas en la riqueza y abundancia en las muestras a través de la diversidad alfa; mientras que la diversidad beta, con la medida Weight UniFrac Bray Curtis, evidencio diferencias entre pacientes y controles, comprobado por la prueba estadística ANOSIM. Adicionalmente, se destaca una disminución en las familias Lactobacillaceae y Streptococcaceae, y un aumento de Lachnospiraceae, Ruminoccocaceae, Verrucomicrobiaceae y Peptostreptococcaceae, esta última es por primera vez descrita como significativa en los casos de Colombia, la cual está implicada en la síntesis de AGCC, degradación de mucina y fibras vegetales, siendo importantes para el mantenimiento de la barrera intestinal y la neuroprotección.Resumen 14 Resumen ejecutivo 16 INTRODUCCIÓN 18 1. ANTECEDENTES 21 2. MARCO TEÓRICO 55 2.1. Enfermedad de Parkinson 55 2.2. Parkinson genético 57 2.2.1. Parkinson clásico 57 2.2.2. Parkinson esporádico o atípico 59 2.3. Parkinson idiopático EPI 59 2.4. Parkinsonismo 60 2.5. Tipos de parkinsonismo 61 2.6. Células dopaminérgicas 62 2.7. Ganglios basales 62 2.8.vías de respuesta motora 64 2.9. Alfa sinucleína 65 2.10. Cuerpos de Lewy 67 2.11. Tratamientos para la enfermedad de Parkinson 69 2.12. Patología de la enfermedad de Parkinson 70 2.13. Vías motoras en la enfermedad de Parkinson 71 2.14. Síntomas de la enfermedad de Parkinson 73 2.14.1. Síntomas motores 73 2.14.2. Síntomas no motores 74 2.15. Microbiota 75 2.16. Microbiota intestinal 76 2.17. Enterotipos 78 2.18. Disbiosis 81 2.19. Metabolitos intestinales e inflamación 83 2.20. Estrés oxidativo en la enfermedad de Parkinson 85 2.21.Interacción alfa sinucleína y metabolitos bacterianos 87 2.22. Disbiosis en la enfermedad de Parkinson 90 2.23. Axis microbiota - intestinal - cerebro 93 2.24. Diversidad de especies 97 2.25. Diversidad alfa 98 2.26. Índices de diversidad 98 2.27. Rarefacción 98 2.28. Diversidad beta 99 2.29. Ordenación de especies 99 2.30. Métodos de ordenación 99 3. DISEÑO METODOLÓGICO 101 3.1. Tipo de investigación 101 3.2. Enfoque, nivel o alcance de la investigación 101 3.3. Hipótesis 101 3.4. Población y muestra 102 3.5. Muestreo 103 3.6. Métodos, técnicas e instrumentos de recolección de datos 103 3.6.1. Antecedentes legales 103 3.7. Variables 108 4. RESULTADOS 115 4.1. Filtros de calidad de secuencias y uso de Qiime 2 112 4.2. Asignación taxonómica de ASV 114 4.3. Rarefacción 114 4.4. Normalización de los datos 115 4.5. Análisis de alfa diversidad 116 4.6. Significancia de la diversidad alfa 118 4.7. Beta diversidad 119 4.7.1. Medidas de distancias, Bray Curtis -NMDS 119 4.7.2. Weight UniFrac 120 4.7.3. Prueba ANOSIM 121 4.7.4. Unweight UniFrac 121 4.7.5. Prueba ANOSIM 122 4.8. Abundancia relativa por familias 123 4.9. Abundancia relativa por filum 125 4.10. Diferencias significativas por bacterias 126 5. DISCUSIÓN 131 6. CONCLUSIONES 140 7. PERSPECTIVAS 143 8. REFERENCIAS BIBLIOGRÁFICAS 144PregradoBacteriólogo(a) y Laboratorista Clínico160p.application/pdfspaUniversidad Colegio Mayor de CundinamarcaFacultad de Ciencias de la SaludBogotá D.CBacteriología y Laboratorio ClínicoDerechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2021https://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/closedAccessAtribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)http://purl.org/coar/access_right/c_14cbCaracterización de la composición bacteriana fecal en pacientes con enfermedad de Parkinson y controles sanos de ColombiaTrabajo de grado - Pregradohttp://purl.org/coar/resource_type/c_7a1fhttp://purl.org/coar/version/c_970fb48d4fbd8a85Textinfo:eu-repo/semantics/bachelorThesishttps://purl.org/redcol/resource_type/TPinfo:eu-repo/semantics/publishedVersionResolución número 8430. [internet] República de Colombia. Bogotá: Ministerio de salud; 1993 [10 de septiembre de 2020]. Recuperado de https://urosario.edu.co/Escuela- Medicina/Investigacion/Documentos-de-inte res/Files/resolucion_008430_1993.pdf.Resolución número 1164. [internet] República de Colombia. Bogotá: Ministerio de salud y Ministerio de ambiente y desarrollo sostenible; 2002 [10 de septiembre de 2020]. Recuperado de http://www.udea.edu.co/wps/wcm/connect/udea/8ef2b54c- c7a3-4d32-8dde- ddf2c0bd9dc9/Resoluci%C3%B3n+1164+de+2002.pdf?MOD= AJPERES.Husebye E. The pathogenesis of gastrointestinal bacterial overgrowth. University Hospital of Oslo. Oslo. Norway, Chemotherapy. [internet] 2005 [cited 16 sept 2020]. vol 51(suppl 1):1–22. Available from doi: 10.1159/000081988.Levy O, Malagelada C & Greene L. Cell death pathways in Parkinson’s disease: proximal triggers, distal effectors, and final steps. Columbia University School of Medicine. New York, NY, USA, review, Springer. [internet] 2009 [cited 16 sept 2020]. vol 14:478–500. Available from doi: 10.1007/s10495-008-0309-3.Hawkes C, Tredici K & Braak H. A timeline for Parkinson’s disease. Deutsche Forschungsgemeinschaft (DFG) and Hilde- Ulrichs Foundation,Germany, Florstadt Staden, review, Elsevier. [internet] 2009 [cited 13 jul 2020]. vol 16, 79–84. Available from doi: 10.1016/j.parkreldis.2009.08.007.Gutierrez J y Singer C- Parkinsonismo: diagnósticos alternativos a la enfermedad idiopática de Parkinson. School of Medicine, Department of Neurology, University of Miami, U.S.A. review, Rev Med Inst Mex Seguro Soc. [internet] 2010 [citado 13 jul 2020]. Vol 48 (3): 279-292. Available from https://www.medigraphic.com/pdfs/imss/im-2010/im103h.pdf.Shulman J, Lager P & Feany M. Parkinson ́s disease: genetics and pathogenesis. University of Alabama, Birmingham. Annual reviews. [internet] 2011 [cited 13 jul 2020]. Vol 6:193–222. Available from doi: 10.1146/annurev-pathol-011110-130242.Elizondo G, Dector M, Martinez H, Martinez L y Esmer M. Genética y la enfermedad de Parkinson: revisiones actualizadas. Departamento de genética de Nuevo México, Elsevier [internet] 2011 [citado 11 de agosto de 2020]. Vol. 13. Issue 51: (96-100), recuperado de: https://www.elsevier.es/en-revista-medicina-universitaria-304- articulo-geneti caenfermedad-parkinson-revision-actualidades- X1665579611240564.Chávez I. Microbiota intestinal en la salud y la enfermedad. Universidad Anáhuac Mayab, Yucatán México. Revista de gastroenterología de México, Elsevier. [internet] 2013 [cited 20 may 2020]. Vol (4):240-248, recuperado de htts://doi.org/10.1016/j.rgmx.2013.04.004.Sonco R. Estudio de la diversidad alfa y beta en tres localidades de un bosque montano en la región de Madidi. La paz – Bolívar. Universidad Mayor de San Andrés. [internet] 2013 [cited 10 de marzo 2021]. Vol 1- 154, recuperado de #search/ljforeror%40unal.edu.co/FMfcgxwKkRPFGjWqddtZZhd WNqgzBnn D?projector=1&messagePartId=0.1.Scheperjans F, Aho V, Pereira P, Koskinen k & Paulin L.Gut Microbiota Are Related to Parkinson’s Disease and Clinical Phenotype. PubMed. [internet] 2014 [cited 23 de may 2019]. Vol: 30(3):350-8, available from: 10.1002/mds.26069.Escobar J, Klotz B, Valdes B E & Agudelo G.M. The gut microbiota of Colombians differs from that of Americans, Europeans and Asians. PubMed [internet] 2014 [ cited el 23 mayo 2019]. Vol: 14;14:311, available from: 10.1186/s12866- 014-0311-6.Keshavarzian A, Green S.J, Engen P.A, Voigt R.M, & Ankur Naqib. Colonic Bacterial Composition in Parkinson’s Disease. PubMed. [internet] 2015 [cited 23 may 2019]. Vol: 30(10):1351- 60, available from: 10.1002/mds.26307.Valenzuela F,Casillas R, Villalpando E y Vargas F. El gen ARNr 16S en el estudio de comunidades microbianas marinas. México. SCielo, [internet] 2015 [cita 20 marzo 2021]. Vol.41 no.4, tomado de: https://doi.org/10.7773/cm.v41i4.2492.Hasegawa S, Goto S, Tsuji H, Okuno T, Asahara T & Nomoto K. Intestinal Dysbiosis and Lowered Serum Lipopolysaccharide- Binding Protein in Parkinson’s Disease. Hertie Institute for Clinical Brain Research and German Center. PLOS. [internet] 2015 [cited 23 may 2020]. Vol 10 (11): e0142164, available from doi: 10.1371 / journal.pone.0142164.Obregon A, Tito R, Metcalf J, Sankaranarayanan K, Clemente J & Ursell L. Subsistence strategies in traditional societies distinguish gut microbiomes. Oklahoma, USA. Nature. [internet] 2015 [cited 10 of march of 2021]. Vol: 6:6505. Retrieved from: doi: 10.1038/ncomms7505.Mardinoglu A, Boren J & Smith U. Confounding Effects of Metformin on the Human Gut Microbiome in Type 2 Diabetes. Stockholm. Cell Press. [internet] 2016 [cited 10 march 2021]. available from: http://dx.doi.org/10.1016/j.cmet.2015.12.012.Unger M, Spiegel J, Dillman K, Grundmann D, Phillippeit H & Burmann J. Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls. Germany. Elsevier. [internet] 2016 [cited 23 may 2020]. 1-7. Available from http://dx.doi.org/10.1016/j.parkreldis.2016.08.019.Patrick P, Etienne C and Stephane H. Understanding Dopaminergic Cell Death Pathways in Parkinson Disease. Neuron. Paris. [internet] 2016 [cited 11/08/20], available from: http://dx.doi.org/10.1016/j.neuron.2016.03.038.Anderson G, Seo M, Berk M, Carvalho A & Maes M. Gut Permeability and Microbiota in Parkinson’s Disease: Role of Depression, Tryptophan Catabolites, Oxidative and Nitrosative Stress and Melatonergic Pathways. UK, London. Review, Bentham Science. [Internet] 2016 [cited 16 sept 2020]. Vol: 22, 6142-6151, available from doi: 10.2174/1381612822666160906161513.Oksanen J. Vegan: ecological diversity, r project. [internet] 2016 [cited 10 of march of 2021]. Available from: https://cran.r- project.org/web/packages/vegan/vignettes/diversity-vegan.pdf.Hopfner F, Künstner A and Müller S. Gut microbiota in Parkinson disease in a northern German cohort. Kiel University, Germany. Elsevier. [internet] 2017 [cited 20 may 2020]. Vol: 41-45. Available from: http://dx.doi.org/10.1016/j.brainres.2017.04.019 0006-8993/ 2017.Callahan B, McMurdie P & Holmes S. Exact sequence variants should replace operational taxonomic units in marker-gene data analysis. USA. The ISME Journa. [internet] 2017 [cited 10 of march of 2021]. Vol: 11, 2639–2643. Available from: https://www.nature.com/articles/ismej2017119.pdf.Klingelhoefer L & Reichmann H. Parkinson’s disease as a multisystem disorder. Department of Neurology. Technical University Dresden, Germany. Springer. [internet] 2017 [cited 20 sept 2020]. Available from: 10.1007/s00702-017-1692-0.Rietdijk C, Perez P, Garssen j, van Weezel R & Kraneveld A. Exploring Braak hypothesis of Parkinson's disease. Netherlands, review, Frontiers in Neurology. [internet] 2017 [cited 20 sep 2020]. Vol: 8: art 37. Available from doi: 10.3389/fneur.2017.00037.Li W, Wu X and Wang T. Structural changes of gut microbiota Parkinson's disease and its correlation with clinical features, Key Laboratory Mental Health.Institute of Psychology. Chinese Academy of Sciences,Beijing. Science China.[internet] 2017 [cited 20 may 2020]. Vol:60 No.11:1223–1233 , Available from: doi: 10.1007/s11427-016-9001-4.Heintz A, Pandey U and Wicke T. The nasal and gut microbiome in Parkinson’s disease and idiopathic rapid eye movement sleep behavior disorder. University of Luxembourg. Esch-sur-Alzette, Luxembourg. Movement Disorders. [internet] 2017 [cited 20 may 2020]. Vol. 33, No. 1, 2018. Available from: DOI: 10.1002/mds.27105.Hill E, Debelius J and Morton J. Parkinson’s disease and PD medications have distinct signatures of the gut microbiome. University of California. San Diego, USA. Mov Disord. [internet] 2017 [cited 20 may 2020]. Vol: 32(5): 739–749. Available from: doi:10.1002/mds.26942.Petrov V, Saltykova I and Zhukova V. Analysis of Gut Microbiota in Patients with Parkinson’s Disease. University, Moscow, Russia. Byulleten’ Eksperimental’noi Biologii i Meditsiny. [internet]. 2017 [cited 20 may 2020]. Vol: 162, No. 12, pp. 700- 703. Available from: doi: 10.1007/s10517-017-3700-7.Gerritsen J, Hornung B, Renckens B, Van S, Martins V & Rijkers G. Genomic and functional analysis of Romboutsia ilealis CRIBT reveals adaptation to the small intestine. The Netherlands, PeerJ, review. [Internet] 2017 [cited 10 march 2021]. Available from: DOI 10.7717/peerj.3698.Marín D, Carmona H, Ibarra M, Gámez M. Enfermedad de Parkinson: fisiopatología, diagnóstico y tratamiento. Rev Univ Ind Santander Salud. [internet] 2018 [cited 11/08/20]. Vol: 50(1): 79-92, recuperado de: doi: 10.18273/revsal.v50n1-2018008.Mulak A. A Controversy on the Role of Short-Chain Fatty Acids in the Pathogenesis of Parkinson’s Disease. Department of Gastroenterology and Hepatology. Wroclaw Medical University, Wroclaw Poland. Movement Disorders. [internet] 2018 [cited 20 may 2020]. Vol. 00, No. 00. available from: DOI: 10.1002/mds.27304.Ma N & Ma X. Dietary Amino Acids and the Gut-Microbiome- Immune Axis: Physiological Metabolism and Therapeutic Prospects. China. Comprehensive, review. [internet] 2018 [cited 10 march 2021]. Vol 18, available from: doi: 10.1111/1541- 4337.12401.Lin A, Zheng W and He Y. Gut microbiota in patients with Parkinson's disease in southern China. Department of Neurology. Zhujiang Hospital, Southern Medical University, Guangzhou, China. Parkinsonism and Related Disorders. [internet] 2018 [cited 20 may 2020]. Vol. 53, 82–88, available from: https://doi.org/10.1016/j.parkreldis.2018.05.007.Fei M and Qin Y. Dysbiosis of gut microbiota and microbial metabolites Parkinson's Disease. Wuxi Medical School, Jiangnan University, Wuxi, China. Elsevier. [Internet] 2018 [cited 20 may 2020]. Vol. 45, 53–61. Available from: https://doi.org/10.1016/j.arr.2018.04.004.Costea P, Hildebrand F, Manimozhiyan A, Bäckhed F, Blaser M & Bushman F. Enterotypes in the landscape of gut microbial community composition. Germany. Review Springer nature. [internet] 2018 [cited 16 sep 2020]. Vol: 3; 8-16. Available from doi: https://doi.org/10.1038/s41564-017-0072-8.Barichella M, Severgnini M, Cilia R, et al. Unraveling gut microbiota in Parkinson’s disease and atypical Parkinsonism, Parkinson Institute, Azienda Socio Sanitaria Territoriale. Milan, Italy. Movement Disorders. [internet] 2018 [cited 20 may 2020]. Available from: doi:10.1002/mds.27581.Liang S, Wu X & Jin F, Gut-Brain Psychology: Rethinking Psychology From the Microbiota–Gut–Brain Axis, University of China. Beijing. Review Frontiers. [internet] 2018 [cited 20 may 2020]. 12: 33. Available from doi: doi: 10.3389/fnint.2018.00033.Fitzgerald E, Murphy S and Martinson H. Alpha-Synuclein Pathology and the Role of the Microbiota in Parkinson’s Disease. USA. Review, Frontiers. [internet] 2019 [cited 9/5/2020]. Available from: https://doi.org/10.3389/fnins.2019.00369.Rusell J, Roesch L, Ördberg M, Ilonen J,Atkinson M & Schatz D. Genetic risk for autoimmunity is associated with distinct changes in the human gut microbiome. USA. Nature. [internet] 2019 [cited 10 march 2021]. Vol: 10:3621. Available from: | https://doi.org/10.1038/s41467-019-11460-x.Rengarajan S, Vivio E, Parkes M, Peterson D, Roberson E & Newberry R. Dynamic immunoglobulin responses to gut bacteria during inflammatory bowel disease. USA, . RENGARAJAN ET AL. [internet] 2019 [cited 10 march 2021]. Vol: 11:3, 405-420. Available from: https://doi.org/10.1080/19490976.2019.1626683.Li C, Cui L and Yang Y. Gut microbiota differs between Parkinson’s disease patients and healthy controls in Northeast China, Department of Neurology and Neuroscience Center, Changchun. China. Front. Mol. Neurosci. [internet] 2019 [cited 20 may 2020]. Available from https://doi.org/10.3389/fnmol.2019.00171.Li F, Wang P, Chen Z, et al. Alteration of the fecal microbiota in North-Eastern Han Chinese population with sporadic Parkinson's disease, Liaoning Province. China. Elsevier [internet] 2019 [cited 20 may 2020]. 707,134297. Available from: https://doi.org/10.1016/j.neulet.2019.134297.Baldini F, Hertel J, Sandt E, et al. Parkinson’s disease- associated alterations of the gut microbiome can invoke disease-relevant metabolic change, Centre for Systems Biomedicine, University of Luxembourg. Luxembourg. bioRxiv [internet] 2019 [cited 20 may 2020]. Available from: http://dx.doi.org/10.1101/691030.Fernandez J y Granados I, Enfermedad de Parkinson: neurodegeneración asociada con el Estrés Oxidativo. Universidad Popular del Cesar, Valledupar. Colombia. Panorama: Cuba y salud. [internet] 2020 [citado 20 mayo 2020]. Vol: ;15(2): 45-52. Available from: http://www.revpanorama.sld.cu/index.php/rpan/article/view/.Oksanen J, Vegan: an introduction to ordination, cran r project. [internet] 2020 [cited 10 march 2021]. Available from: https://cran.r-project.org/web/packages/vegan/vignettes/intro- vegan.pdf.Zhang F, Zhao Q, Fang X, Xu M, Tang J & Zhang Y. Metagenomic analysis of gut microbiota in Parkinson's disease patients from Central China, Hubei University of Medicine. China. Research Square. [internet] 2020 [cited 10 oct 2020]. Available from doi:10.21203/rs.2.21271/v2.Arkesenen D, Weimers P, Marker D ,Johannesen T ,Iversen S & Lilje B. Disease activity measures are related to the faecal gut microbiota in adult patients with ulcerative colitis. USA. Taylor y Francis. [internet] 2020 [cited 20 march 2021]. Available from: https://doi.org/10.1080/00365521.2020.1829031.Kitamono S, Kitamono H, Hein R, Schmidt T & Kamada N. The Bacterial Connection between the Oral Cavity and the Gut Diseases. USA. Journal of Dental Research. [internet] 2020 [cited 20 march 2021]. Vol: 1-9. Available from: DOI: 10.1177/0022034520924633 journal.Composición bacterianaTrastorno neurodegenerativoCélulas dopaminérgicasEnfermedad de ParkinsonParkinson idiopáticomicrobiota intestinalDisbiosis intestinalMetabolitos bacterianosNeuroinflamaciónSistema nervioso centralSistema nervioso entéricoORIGINALNatalia Arias Rodríguez Caracterización de la composición bacteriana fecal de pacientes con EP y controles sanos de Colombia Natalia Arias.pdfNatalia Arias Rodríguez Caracterización de la composición bacteriana fecal de pacientes con EP y controles sanos de Colombia Natalia Arias.pdfapplication/pdf3538634https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/1/Natalia%20Arias%20Rodr%c3%adguez%20Caracterizaci%c3%b3n%20de%20la%20composici%c3%b3n%20bacteriana%20fecal%20de%20pacientes%20con%20EP%20y%20controles%20sanos%20de%20Colombia%20Natalia%20Arias.pdfa2a72b602d8ca6e117a52816a73b6250MD51open accessFORMATO DERECHOS DE AUTOR TG 2021 (2).pdfFORMATO DERECHOS DE AUTOR TG 2021 (2).pdfapplication/pdf343525https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/2/FORMATO%20DERECHOS%20DE%20AUTOR%20TG%202021%20%20%282%29.pdfb583ddaabe2ab727e14295f660aa4ca4MD52metadata only accessFormato decanatura 3.pdfFormato decanatura 3.pdfapplication/pdf78131https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/3/Formato%20decanatura%203.pdf5c9d711032dad99cde9e1ad597973c9bMD53metadata only accessNatalia Arias Rodríguez Trabajo de grado Natalia Arias.pdfNatalia Arias Rodríguez Trabajo de grado Natalia Arias.pdfapplication/pdf7340032https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/4/Natalia%20Arias%20Rodr%c3%adguez%20Trabajo%20de%20grado%20Natalia%20Arias.pdf35d40ab17eeaf81dd8b8276d556da31aMD54open accessLICENSElicense.txtlicense.txttext/plain; charset=utf-814828https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/5/license.txt2f9959eaf5b71fae44bbf9ec84150c7aMD55open accessTEXTNatalia Arias Rodríguez Caracterización de la composición bacteriana fecal de pacientes con EP y controles sanos de Colombia Natalia Arias.pdf.txtNatalia Arias Rodríguez Caracterización de la composición bacteriana fecal de pacientes con EP y controles sanos de Colombia Natalia Arias.pdf.txtExtracted texttext/plain17728https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/6/Natalia%20Arias%20Rodr%c3%adguez%20Caracterizaci%c3%b3n%20de%20la%20composici%c3%b3n%20bacteriana%20fecal%20de%20pacientes%20con%20EP%20y%20controles%20sanos%20de%20Colombia%20Natalia%20Arias.pdf.txt52722c26a2cd6aba40e43519bce7102fMD56open accessFORMATO DERECHOS DE AUTOR TG 2021 (2).pdf.txtFORMATO DERECHOS DE AUTOR TG 2021 (2).pdf.txtExtracted texttext/plain1822https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/8/FORMATO%20DERECHOS%20DE%20AUTOR%20TG%202021%20%20%282%29.pdf.txt31a660745e377a2c7c1d4be1f6637b30MD58metadata only accessFormato decanatura 3.pdf.txtFormato decanatura 3.pdf.txtExtracted texttext/plain1https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/10/Formato%20decanatura%203.pdf.txt68b329da9893e34099c7d8ad5cb9c940MD510metadata only accessTHUMBNAILNatalia Arias Rodríguez Caracterización de la composición bacteriana fecal de pacientes con EP y controles sanos de Colombia Natalia Arias.pdf.jpgNatalia Arias Rodríguez Caracterización de la composición bacteriana fecal de pacientes con EP y controles sanos de Colombia Natalia Arias.pdf.jpgGenerated Thumbnailimage/jpeg7929https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/7/Natalia%20Arias%20Rodr%c3%adguez%20Caracterizaci%c3%b3n%20de%20la%20composici%c3%b3n%20bacteriana%20fecal%20de%20pacientes%20con%20EP%20y%20controles%20sanos%20de%20Colombia%20Natalia%20Arias.pdf.jpg745ef94c2bf699d936c0b468aa75be12MD57open accessFORMATO DERECHOS DE AUTOR TG 2021 (2).pdf.jpgFORMATO DERECHOS DE AUTOR TG 2021 (2).pdf.jpgGenerated Thumbnailimage/jpeg12002https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/9/FORMATO%20DERECHOS%20DE%20AUTOR%20TG%202021%20%20%282%29.pdf.jpga9a977f10b92c5488e375b9ca97e5d26MD59metadata only accessFormato decanatura 3.pdf.jpgFormato decanatura 3.pdf.jpgGenerated Thumbnailimage/jpeg8378https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/2834/11/Formato%20decanatura%203.pdf.jpg125acae089e6ede6cb20d1f11fb40437MD511metadata only accessunicolmayor/2834oai:repositorio.unicolmayor.edu.co:unicolmayor/28342021-09-10 03:00:21.154An error occurred on the license name.|||https://creativecommons.org/licenses/by-nc-sa/4.0/open accessBiblioteca Digital Unicolmayorrepositorio@unicolmayor.edu.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 |