Relationship between skin and gut microbiota dysbiosis and inflammatory skin diseases in adult patients: A systematic review
Introduction: The skin and gut microbiota significantly contribute to the body's homeostasis by modulating immune responses and protecting against pathogens. Dysbiosis, an imbalance in microbial communities, is increasingly recognized in inflammatory skin diseases such as psoriasis, atopic derm...
- Autores:
-
Sánchez López, Maria Fernanda
Barrero Caicedo, Paula Alejandra
Olmos Carval, Helen Melissa
Torres Medina, Andres Felipe
Alzate, Juan Pablo
- Tipo de recurso:
- Article of investigation
- Fecha de publicación:
- 2025
- Institución:
- Universidad de Ciencias Aplicadas y Ambientales U.D.C.A
- Repositorio:
- Repositorio Institucional UDCA
- Idioma:
- eng
- OAI Identifier:
- oai:repository.udca.edu.co:11158/6286
- Acceso en línea:
- https://repository.udca.edu.co/handle/11158/6286
https://doi.org/10.1016/j.microb.2025.100342
https://repository.udca.edu.co/
- Palabra clave:
- 610 - Medicina y salud::616 - Enfermedades
Microbiota
Enfermedades de la Piel
Disbiosis
Microbioma Gastrointestinal
Gut-skin axis
Disbiosis
- Rights
- openAccess
- License
- https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode.es
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dc.title.eng.fl_str_mv |
Relationship between skin and gut microbiota dysbiosis and inflammatory skin diseases in adult patients: A systematic review |
title |
Relationship between skin and gut microbiota dysbiosis and inflammatory skin diseases in adult patients: A systematic review |
spellingShingle |
Relationship between skin and gut microbiota dysbiosis and inflammatory skin diseases in adult patients: A systematic review 610 - Medicina y salud::616 - Enfermedades Microbiota Enfermedades de la Piel Disbiosis Microbioma Gastrointestinal Gut-skin axis Disbiosis |
title_short |
Relationship between skin and gut microbiota dysbiosis and inflammatory skin diseases in adult patients: A systematic review |
title_full |
Relationship between skin and gut microbiota dysbiosis and inflammatory skin diseases in adult patients: A systematic review |
title_fullStr |
Relationship between skin and gut microbiota dysbiosis and inflammatory skin diseases in adult patients: A systematic review |
title_full_unstemmed |
Relationship between skin and gut microbiota dysbiosis and inflammatory skin diseases in adult patients: A systematic review |
title_sort |
Relationship between skin and gut microbiota dysbiosis and inflammatory skin diseases in adult patients: A systematic review |
dc.creator.fl_str_mv |
Sánchez López, Maria Fernanda Barrero Caicedo, Paula Alejandra Olmos Carval, Helen Melissa Torres Medina, Andres Felipe Alzate, Juan Pablo |
dc.contributor.author.none.fl_str_mv |
Sánchez López, Maria Fernanda Barrero Caicedo, Paula Alejandra Olmos Carval, Helen Melissa Torres Medina, Andres Felipe Alzate, Juan Pablo |
dc.subject.ddc.none.fl_str_mv |
610 - Medicina y salud::616 - Enfermedades |
topic |
610 - Medicina y salud::616 - Enfermedades Microbiota Enfermedades de la Piel Disbiosis Microbioma Gastrointestinal Gut-skin axis Disbiosis |
dc.subject.armarc.none.fl_str_mv |
Microbiota |
dc.subject.decs.none.fl_str_mv |
Enfermedades de la Piel Disbiosis Microbioma Gastrointestinal |
dc.subject.proposal.eng.fl_str_mv |
Gut-skin axis |
dc.subject.ecm.none.fl_str_mv |
Disbiosis |
description |
Introduction: The skin and gut microbiota significantly contribute to the body's homeostasis by modulating immune responses and protecting against pathogens. Dysbiosis, an imbalance in microbial communities, is increasingly recognized in inflammatory skin diseases such as psoriasis, atopic dermatitis, and rosacea. These diseases are interconnected through the gut-skin axis, involving complex immunological and neuroendocrine mechanisms. Understanding this bidirectional interaction is crucial, as it implies that alterations in gut microbiota can impact skin health and vice versa. Objective: This systematic review aims to evaluate the association between dysbiosis of skin and gut microbiota and inflammatory skin diseases in adult patients, and to assess the efficacy of various therapeutic interventions targeting microbiota dysbiosis. Methods: A systematic search was conducted in MEDLINE, Embase, Cochrane Library, Scopus, and Web of Science to identify experimental studies and clinical trials exploring microbiota dysbiosis in adults with inflammatory skin diseases. Inclusion criteria were studies employing genetic sequencing or microbiological culture methods, along with interventions such as probiotics or fecal transplants. Results: From the initial 1279 studies identified, 19 met the inclusion criteria. In patients with psoriasis, gut microbiota exhibited decreased Actinobacteria and increased Firmicutes, correlating with elevated inflammatory markers. Atopic dermatitis was characterized by reduced populations of beneficial bacteria, particularly Bifidobacterium and Lactobacillus, significantly associated with skin flare-ups and disease severity. Therapeutic interventions with probiotics demonstrated improvement in microbial diversity and a reduction in inflammation across several inflammatory skin conditions, including psoriasis and atopic dermatitis. Discussion: The findings underscore the significant role microbial dysbiosis plays in the pathogenesis of inflammatory skin diseases. Microbiota modulation through probiotics and prebiotics emerges as a promising therapeutic approach. However, due to heterogeneity among reviewed studies, further controlled research is essential to confirm the long-term efficacy and mechanisms of microbiota-targeted interventions. |
publishDate |
2025 |
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2025-05-12T19:49:33Z |
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2025-05-12T19:49:33Z |
dc.date.issued.none.fl_str_mv |
2025 |
dc.type.none.fl_str_mv |
Artículo de revista |
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http://purl.org/coar/resource_type/c_2df8fbb1 |
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Sanchez-Lopez, M. F., Barrero-Caicedo, P. A., Olmos-Carval, H. M., Torres-Medina, A. F., & Alzate-Granados, J. P. (2025). Relationship between skin and gut microbiota dysbiosis and inflammatory skin diseases in adult patients: A systematic review. The Microbe, 7(100342), 100342. https://doi.org/10.1016/j.microb.2025.100342 |
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29501946 |
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https://repository.udca.edu.co/handle/11158/6286 |
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https://doi.org/10.1016/j.microb.2025.100342 |
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Universidad de Ciencias Aplicadas y Ambientales |
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UDCA |
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https://repository.udca.edu.co/ |
identifier_str_mv |
Sanchez-Lopez, M. F., Barrero-Caicedo, P. A., Olmos-Carval, H. M., Torres-Medina, A. F., & Alzate-Granados, J. P. (2025). Relationship between skin and gut microbiota dysbiosis and inflammatory skin diseases in adult patients: A systematic review. The Microbe, 7(100342), 100342. https://doi.org/10.1016/j.microb.2025.100342 29501946 Universidad de Ciencias Aplicadas y Ambientales UDCA |
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https://repository.udca.edu.co/handle/11158/6286 https://doi.org/10.1016/j.microb.2025.100342 https://repository.udca.edu.co/ |
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eng |
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eng |
dc.relation.indexed.none.fl_str_mv |
LaReferencia |
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(Jun., 2025) Artículo número 100342 |
dc.relation.citationendpage.none.fl_str_mv |
8 |
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1 |
dc.relation.citationvolume.none.fl_str_mv |
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Microbe (Netherlands) |
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https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode.es |
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Atribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0) |
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openAccess |
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Sánchez López, Maria FernandaBarrero Caicedo, Paula AlejandraOlmos Carval, Helen MelissaTorres Medina, Andres Felipevirtual::565-1Alzate, Juan Pablovirtual::566-12025-05-12T19:49:33Z2025-05-12T19:49:33Z2025Sanchez-Lopez, M. F., Barrero-Caicedo, P. A., Olmos-Carval, H. M., Torres-Medina, A. F., & Alzate-Granados, J. P. (2025). Relationship between skin and gut microbiota dysbiosis and inflammatory skin diseases in adult patients: A systematic review. The Microbe, 7(100342), 100342. https://doi.org/10.1016/j.microb.2025.10034229501946https://repository.udca.edu.co/handle/11158/6286https://doi.org/10.1016/j.microb.2025.100342Universidad de Ciencias Aplicadas y AmbientalesUDCAhttps://repository.udca.edu.co/Introduction: The skin and gut microbiota significantly contribute to the body's homeostasis by modulating immune responses and protecting against pathogens. Dysbiosis, an imbalance in microbial communities, is increasingly recognized in inflammatory skin diseases such as psoriasis, atopic dermatitis, and rosacea. These diseases are interconnected through the gut-skin axis, involving complex immunological and neuroendocrine mechanisms. Understanding this bidirectional interaction is crucial, as it implies that alterations in gut microbiota can impact skin health and vice versa. Objective: This systematic review aims to evaluate the association between dysbiosis of skin and gut microbiota and inflammatory skin diseases in adult patients, and to assess the efficacy of various therapeutic interventions targeting microbiota dysbiosis. Methods: A systematic search was conducted in MEDLINE, Embase, Cochrane Library, Scopus, and Web of Science to identify experimental studies and clinical trials exploring microbiota dysbiosis in adults with inflammatory skin diseases. Inclusion criteria were studies employing genetic sequencing or microbiological culture methods, along with interventions such as probiotics or fecal transplants. Results: From the initial 1279 studies identified, 19 met the inclusion criteria. In patients with psoriasis, gut microbiota exhibited decreased Actinobacteria and increased Firmicutes, correlating with elevated inflammatory markers. Atopic dermatitis was characterized by reduced populations of beneficial bacteria, particularly Bifidobacterium and Lactobacillus, significantly associated with skin flare-ups and disease severity. Therapeutic interventions with probiotics demonstrated improvement in microbial diversity and a reduction in inflammation across several inflammatory skin conditions, including psoriasis and atopic dermatitis. Discussion: The findings underscore the significant role microbial dysbiosis plays in the pathogenesis of inflammatory skin diseases. Microbiota modulation through probiotics and prebiotics emerges as a promising therapeutic approach. However, due to heterogeneity among reviewed studies, further controlled research is essential to confirm the long-term efficacy and mechanisms of microbiota-targeted interventions.Incluye referencias bibliográficasapplication/pdfenghttps://creativecommons.org/licenses/by-nc-sa/4.0/legalcode.eshttps://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessAtribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)http://purl.org/coar/access_right/c_abf2https://www.sciencedirect.com/science/article/pii/S2950194625001104?pes=vor&utm_source=scopus&getft_integrator=scopus610 - Medicina y salud::616 - EnfermedadesMicrobiotaEnfermedades de la PielDisbiosisMicrobioma GastrointestinalGut-skin axisDisbiosisRelationship between skin and gut microbiota dysbiosis and inflammatory skin diseases in adult patients: A systematic reviewArtículo de 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jecuta públicamente en forma digital la Obra o cualquier Obra Derivada u Obra Colectiva, Usted debe mantener intacta toda la información de derecho de autor de la Obra y proporcionar, de forma razonable según el medio o manera que Usted esté utilizando: (i) el nombre del Autor Original si está provisto (o seudónimo, si fuere aplicable), y/o (ii) el nombre de la parte o las partes que el Autor Original y/o el Licenciante hubieren designado para la atribución (v.g., un instituto patrocinador, editorial, publicación) en la información de los derechos de autor del Licenciante, términos de servicios o de otras formas razonables; el título de la Obra si está provisto; en la medida de lo razonablemente factible y, si está provisto, el Identificador Uniforme de Recursos (Uniform Resource Identifier) que el Licenciante especifica para ser asociado con la Obra, salvo que tal URI no se refiera a la nota sobre los derechos de autor o a la información sobre el licenciamiento de la Obra; y en el caso de una Obra Derivada, atribuir el crédito identificando el uso de la Obra en la Obra Derivada (v.g., "Traducción Francesa de la Obra del Autor Original," o "Guión Cinematográfico basado en la Obra original del Autor Original"). Tal crédito puede ser implementado de cualquier forma razonable; en el caso, sin embargo, de Obras Derivadas u Obras Colectivas, tal crédito aparecerá, como mínimo, donde aparece el crédito de cualquier otro autor comparable y de una manera, al menos, tan destacada como el crédito de otro autor comparable.</li>
      <li>
        Para evitar toda confusión, el Licenciante aclara que, cuando la obra es una composición musical:
        <ol type="i">
          <li>Regalías por interpretación y ejecución bajo licencias generales. El Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública o la ejecución pública digital de la obra y de recolectar, sea individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, SAYCO), las regalías por la ejecución pública o por la ejecución pública digital de la obra (por ejemplo Webcast) licenciada bajo licencias generales, si la interpretación o ejecución de la obra está primordialmente orientada por o dirigida a la obtención de una ventaja comercial o una compensación monetaria privada.</li>
          <li>Regalías por Fonogramas. El Licenciante se reserva el derecho exclusivo de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, los consagrados por la SAYCO), una agencia de derechos musicales o algún agente designado, las regalías por cualquier fonograma que Usted cree a partir de la obra (“versión cover”) y distribuya, en los términos del régimen de derechos de autor, si la creación o distribución de esa versión cover está primordialmente destinada o dirigida a obtener una ventaja comercial o una compensación monetaria privada.</li>
        </ol>
      </li>
      <li>Gestión de Derechos de Autor sobre Interpretaciones y Ejecuciones Digitales (WebCasting). Para evitar toda confusión, el Licenciante aclara que, cuando la obra sea un fonograma, el Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública digital de la obra (por ejemplo, webcast) y de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, ACINPRO), las regalías por la ejecución pública digital de la obra (por ejemplo, webcast), sujeta a las disposiciones aplicables del régimen de Derecho de Autor, si esta ejecución pública digital está primordialmente dirigida a obtener una ventaja comercial o una compensación monetaria privada.</li>
    </ol>
  </li>
  <br/>
  <li>
    Representaciones, Garantías y Limitaciones de Responsabilidad.
    <p>A MENOS QUE LAS PARTES LO ACORDARAN DE OTRA FORMA POR ESCRITO, EL LICENCIANTE OFRECE LA OBRA (EN EL ESTADO EN EL QUE SE ENCUENTRA) “TAL CUAL”, SIN BRINDAR GARANTÍAS DE CLASE ALGUNA RESPECTO DE LA OBRA, YA SEA EXPRESA, IMPLÍCITA, LEGAL O CUALQUIERA OTRA, INCLUYENDO, SIN LIMITARSE A ELLAS, GARANTÍAS DE TITULARIDAD, COMERCIABILIDAD, ADAPTABILIDAD O ADECUACIÓN A PROPÓSITO DETERMINADO, AUSENCIA DE INFRACCIÓN, DE AUSENCIA DE DEFECTOS LATENTES O DE OTRO TIPO, O LA PRESENCIA O AUSENCIA DE ERRORES, SEAN O NO DESCUBRIBLES (PUEDAN O NO SER ESTOS DESCUBIERTOS). ALGUNAS JURISDICCIONES NO PERMITEN LA EXCLUSIÓN DE GARANTÍAS IMPLÍCITAS, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.</p>
  </li>
  <br/>
  <li>
    Limitación de responsabilidad.
    <p>A MENOS QUE LO EXIJA EXPRESAMENTE LA LEY APLICABLE, EL LICENCIANTE NO SERÁ RESPONSABLE ANTE USTED POR DAÑO ALGUNO, SEA POR RESPONSABILIDAD EXTRACONTRACTUAL, PRECONTRACTUAL O CONTRACTUAL, OBJETIVA O SUBJETIVA, SE TRATE DE DAÑOS MORALES O PATRIMONIALES, DIRECTOS O INDIRECTOS, PREVISTOS O IMPREVISTOS PRODUCIDOS POR EL USO DE ESTA LICENCIA O DE LA OBRA, AUN CUANDO EL LICENCIANTE HAYA SIDO ADVERTIDO DE LA POSIBILIDAD DE DICHOS DAÑOS. ALGUNAS LEYES NO PERMITEN LA EXCLUSIÓN DE CIERTA RESPONSABILIDAD, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.</p>
  </li>
  <br/>
  <li>
    Término.
    <ol type="a">
      <li>Esta Licencia y los derechos otorgados en virtud de ella terminarán automáticamente si Usted infringe alguna condición establecida en ella. Sin embargo, los individuos o entidades que han recibido Obras Derivadas o Colectivas de Usted de conformidad con esta Licencia, no verán terminadas sus licencias, siempre que estos individuos o entidades sigan cumpliendo íntegramente las condiciones de estas licencias. Las Secciones 1, 2, 5, 6, 7, y 8 subsistirán a cualquier terminación de esta Licencia.</li>
      <li>Sujeta a las condiciones y términos anteriores, la licencia otorgada aquí es perpetua (durante el período de vigencia de los derechos de autor de la obra). No obstante lo anterior, el Licenciante se reserva el derecho a publicar y/o estrenar la Obra bajo condiciones de licencia diferentes o a dejar de distribuirla en los términos de esta Licencia en cualquier momento; en el entendido, sin embargo, que esa elección no servirá para revocar esta licencia o que deba ser otorgada , bajo los términos de esta licencia), y esta licencia continuará en pleno vigor y efecto a menos que sea terminada como se expresa atrás. La Licencia revocada continuará siendo plenamente vigente y efectiva si no se le da término en las condiciones indicadas anteriormente.</li>
    </ol>
  </li>
  <br/>
  <li>
    Varios.
    <ol type="a">
      <li>Cada vez que Usted distribuya o ponga a disposición pública la Obra o una Obra Colectiva, el Licenciante ofrecerá al destinatario una licencia en los mismos términos y condiciones que la licencia otorgada a Usted bajo esta Licencia.</li>
      <li>Si alguna disposición de esta Licencia resulta invalidada o no exigible, según la legislación vigente, esto no afectará ni la validez ni la aplicabilidad del resto de condiciones de esta Licencia y, sin acción adicional por parte de los sujetos de este acuerdo, aquélla se entenderá reformada lo mínimo necesario para hacer que dicha disposición sea válida y exigible.</li>
      <li>Ningún término o disposición de esta Licencia se estimará renunciada y ninguna violación de ella será consentida a menos que esa renuncia o consentimiento sea otorgado por escrito y firmado por la parte que renuncie o consienta.</li>
      <li>Esta Licencia refleja el acuerdo pleno entre las partes respecto a la Obra aquí licenciada. No hay arreglos, acuerdos o declaraciones respecto a la Obra que no estén especificados en este documento. El Licenciante no se verá limitado por ninguna disposición adicional que pueda surgir en alguna comunicación emanada de Usted. Esta Licencia no puede ser modificada sin el consentimiento mutuo por escrito del Licenciante y Usted.</li>
    </ol>
  </li>
  <br/>
</ol>
 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