Metabolic dysfunction-associated steatotic liver disease exhibits sex-specific microbial heterogeneity within intestinal compartments

Autores
Pirola, Carlos Jose; Landa, Maria Silvina; Schuman, Mariano Luis; Garcia, Silvia Ines; Salatino, Adrián Emanuel; Sookoian, Silvia Cristina
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background/Aims: Evidence suggests that the gastrointestinal microbiome plays a significant role in the biology of metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether disparities in the gut microbiome across intestinal tissular compartments between the sexes lead to MASLD pathogenesis. Methods: Sex-specific analyses of microbiome composition in two anatomically distinct regions of the gut, the small intestine and colon, were performed using an experimental model of MASLD. The study involved male and female spontaneously hypertensive rats and the Wistar-Kyoto control rat strain, which were fed either a standard chow diet or a high-fat diet for 12 weeks to induce MASLD (12 rats per group). High-throughput 16S sequencing was used for microbiome analysis. Results: There were significant differences in the overall microbiome composition of male and female rats with MASLD, including variations in topographical gut regions. The beta diversity of the jejunal and colon microbiomes was higher in female rats than in male rats (PERMANOVA P-value=0.001). Sex-specific analysis and discriminant features using LEfSe showed considerable variation in bacterial abundance, along with distinct functional properties, in the jejunum and colon of animals with MASLD. Significantly elevated levels of lipopolysaccharide and protein expression of Toll-like receptor 4 were observed in the livers of male rats with MASLD compared with their female counterparts. Conclusions: This study uncovered sexual dimorphism in the gut microbiome of MASLD and identified microbial heterogeneity within intestinal compartments. Insights into sex-specific variations in gut microbiome composition could facilitate customised treatment strategies.
Fil: Pirola, Carlos Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Facultad de Ciencias de la Salud. Centro de Investigación Traslacional en Salud;
Fil: Landa, Maria Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Schuman, Mariano Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Garcia, Silvia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Hospital Alemán; Argentina
Fil: Salatino, Adrián Emanuel. Max Planck Institute for Immunobiology and Epigenetics; Alemania
Fil: Sookoian, Silvia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Facultad de Ciencias de la Salud. Centro de Investigación Traslacional en Salud;
Materia
MASLD
NAFLD
METABOLIC SYNDROME
SEXUAL DIMORPHISM
GUT MICROBIOME
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/261615

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network_name_str CONICET Digital (CONICET)
spelling Metabolic dysfunction-associated steatotic liver disease exhibits sex-specific microbial heterogeneity within intestinal compartmentsPirola, Carlos JoseLanda, Maria SilvinaSchuman, Mariano LuisGarcia, Silvia InesSalatino, Adrián EmanuelSookoian, Silvia CristinaMASLDNAFLDMETABOLIC SYNDROMESEXUAL DIMORPHISMGUT MICROBIOMEhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Background/Aims: Evidence suggests that the gastrointestinal microbiome plays a significant role in the biology of metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether disparities in the gut microbiome across intestinal tissular compartments between the sexes lead to MASLD pathogenesis. Methods: Sex-specific analyses of microbiome composition in two anatomically distinct regions of the gut, the small intestine and colon, were performed using an experimental model of MASLD. The study involved male and female spontaneously hypertensive rats and the Wistar-Kyoto control rat strain, which were fed either a standard chow diet or a high-fat diet for 12 weeks to induce MASLD (12 rats per group). High-throughput 16S sequencing was used for microbiome analysis. Results: There were significant differences in the overall microbiome composition of male and female rats with MASLD, including variations in topographical gut regions. The beta diversity of the jejunal and colon microbiomes was higher in female rats than in male rats (PERMANOVA P-value=0.001). Sex-specific analysis and discriminant features using LEfSe showed considerable variation in bacterial abundance, along with distinct functional properties, in the jejunum and colon of animals with MASLD. Significantly elevated levels of lipopolysaccharide and protein expression of Toll-like receptor 4 were observed in the livers of male rats with MASLD compared with their female counterparts. Conclusions: This study uncovered sexual dimorphism in the gut microbiome of MASLD and identified microbial heterogeneity within intestinal compartments. Insights into sex-specific variations in gut microbiome composition could facilitate customised treatment strategies.Fil: Pirola, Carlos Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Facultad de Ciencias de la Salud. Centro de Investigación Traslacional en Salud;Fil: Landa, Maria Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Schuman, Mariano Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Garcia, Silvia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Hospital Alemán; ArgentinaFil: Salatino, Adrián Emanuel. Max Planck Institute for Immunobiology and Epigenetics; AlemaniaFil: Sookoian, Silvia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Facultad de Ciencias de la Salud. Centro de Investigación Traslacional en Salud;Korean Association for the Study of the Liver2024-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/261615Pirola, Carlos Jose; Landa, Maria Silvina; Schuman, Mariano Luis; Garcia, Silvia Ines; Salatino, Adrián Emanuel; et al.; Metabolic dysfunction-associated steatotic liver disease exhibits sex-specific microbial heterogeneity within intestinal compartments; Korean Association for the Study of the Liver; Clinical and Molecular Hepatology; 31; 1; 10-2024; 179-1952287-27282287-285XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.e-cmh.org/journal/view.php?doi=10.3350/cmh.2024.0359info:eu-repo/semantics/altIdentifier/doi/10.3350/cmh.2024.0359info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:14Zoai:ri.conicet.gov.ar:11336/261615instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:59:14.421CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Metabolic dysfunction-associated steatotic liver disease exhibits sex-specific microbial heterogeneity within intestinal compartments
title Metabolic dysfunction-associated steatotic liver disease exhibits sex-specific microbial heterogeneity within intestinal compartments
spellingShingle Metabolic dysfunction-associated steatotic liver disease exhibits sex-specific microbial heterogeneity within intestinal compartments
Pirola, Carlos Jose
MASLD
NAFLD
METABOLIC SYNDROME
SEXUAL DIMORPHISM
GUT MICROBIOME
title_short Metabolic dysfunction-associated steatotic liver disease exhibits sex-specific microbial heterogeneity within intestinal compartments
title_full Metabolic dysfunction-associated steatotic liver disease exhibits sex-specific microbial heterogeneity within intestinal compartments
title_fullStr Metabolic dysfunction-associated steatotic liver disease exhibits sex-specific microbial heterogeneity within intestinal compartments
title_full_unstemmed Metabolic dysfunction-associated steatotic liver disease exhibits sex-specific microbial heterogeneity within intestinal compartments
title_sort Metabolic dysfunction-associated steatotic liver disease exhibits sex-specific microbial heterogeneity within intestinal compartments
dc.creator.none.fl_str_mv Pirola, Carlos Jose
Landa, Maria Silvina
Schuman, Mariano Luis
Garcia, Silvia Ines
Salatino, Adrián Emanuel
Sookoian, Silvia Cristina
author Pirola, Carlos Jose
author_facet Pirola, Carlos Jose
Landa, Maria Silvina
Schuman, Mariano Luis
Garcia, Silvia Ines
Salatino, Adrián Emanuel
Sookoian, Silvia Cristina
author_role author
author2 Landa, Maria Silvina
Schuman, Mariano Luis
Garcia, Silvia Ines
Salatino, Adrián Emanuel
Sookoian, Silvia Cristina
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv MASLD
NAFLD
METABOLIC SYNDROME
SEXUAL DIMORPHISM
GUT MICROBIOME
topic MASLD
NAFLD
METABOLIC SYNDROME
SEXUAL DIMORPHISM
GUT MICROBIOME
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background/Aims: Evidence suggests that the gastrointestinal microbiome plays a significant role in the biology of metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether disparities in the gut microbiome across intestinal tissular compartments between the sexes lead to MASLD pathogenesis. Methods: Sex-specific analyses of microbiome composition in two anatomically distinct regions of the gut, the small intestine and colon, were performed using an experimental model of MASLD. The study involved male and female spontaneously hypertensive rats and the Wistar-Kyoto control rat strain, which were fed either a standard chow diet or a high-fat diet for 12 weeks to induce MASLD (12 rats per group). High-throughput 16S sequencing was used for microbiome analysis. Results: There were significant differences in the overall microbiome composition of male and female rats with MASLD, including variations in topographical gut regions. The beta diversity of the jejunal and colon microbiomes was higher in female rats than in male rats (PERMANOVA P-value=0.001). Sex-specific analysis and discriminant features using LEfSe showed considerable variation in bacterial abundance, along with distinct functional properties, in the jejunum and colon of animals with MASLD. Significantly elevated levels of lipopolysaccharide and protein expression of Toll-like receptor 4 were observed in the livers of male rats with MASLD compared with their female counterparts. Conclusions: This study uncovered sexual dimorphism in the gut microbiome of MASLD and identified microbial heterogeneity within intestinal compartments. Insights into sex-specific variations in gut microbiome composition could facilitate customised treatment strategies.
Fil: Pirola, Carlos Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Facultad de Ciencias de la Salud. Centro de Investigación Traslacional en Salud;
Fil: Landa, Maria Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Schuman, Mariano Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Garcia, Silvia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Hospital Alemán; Argentina
Fil: Salatino, Adrián Emanuel. Max Planck Institute for Immunobiology and Epigenetics; Alemania
Fil: Sookoian, Silvia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Facultad de Ciencias de la Salud. Centro de Investigación Traslacional en Salud;
description Background/Aims: Evidence suggests that the gastrointestinal microbiome plays a significant role in the biology of metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether disparities in the gut microbiome across intestinal tissular compartments between the sexes lead to MASLD pathogenesis. Methods: Sex-specific analyses of microbiome composition in two anatomically distinct regions of the gut, the small intestine and colon, were performed using an experimental model of MASLD. The study involved male and female spontaneously hypertensive rats and the Wistar-Kyoto control rat strain, which were fed either a standard chow diet or a high-fat diet for 12 weeks to induce MASLD (12 rats per group). High-throughput 16S sequencing was used for microbiome analysis. Results: There were significant differences in the overall microbiome composition of male and female rats with MASLD, including variations in topographical gut regions. The beta diversity of the jejunal and colon microbiomes was higher in female rats than in male rats (PERMANOVA P-value=0.001). Sex-specific analysis and discriminant features using LEfSe showed considerable variation in bacterial abundance, along with distinct functional properties, in the jejunum and colon of animals with MASLD. Significantly elevated levels of lipopolysaccharide and protein expression of Toll-like receptor 4 were observed in the livers of male rats with MASLD compared with their female counterparts. Conclusions: This study uncovered sexual dimorphism in the gut microbiome of MASLD and identified microbial heterogeneity within intestinal compartments. Insights into sex-specific variations in gut microbiome composition could facilitate customised treatment strategies.
publishDate 2024
dc.date.none.fl_str_mv 2024-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/261615
Pirola, Carlos Jose; Landa, Maria Silvina; Schuman, Mariano Luis; Garcia, Silvia Ines; Salatino, Adrián Emanuel; et al.; Metabolic dysfunction-associated steatotic liver disease exhibits sex-specific microbial heterogeneity within intestinal compartments; Korean Association for the Study of the Liver; Clinical and Molecular Hepatology; 31; 1; 10-2024; 179-195
2287-2728
2287-285X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/261615
identifier_str_mv Pirola, Carlos Jose; Landa, Maria Silvina; Schuman, Mariano Luis; Garcia, Silvia Ines; Salatino, Adrián Emanuel; et al.; Metabolic dysfunction-associated steatotic liver disease exhibits sex-specific microbial heterogeneity within intestinal compartments; Korean Association for the Study of the Liver; Clinical and Molecular Hepatology; 31; 1; 10-2024; 179-195
2287-2728
2287-285X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.3350/cmh.2024.0359
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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rights_invalid_str_mv https://creativecommons.org/licenses/by-nc/2.5/ar/
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dc.publisher.none.fl_str_mv Korean Association for the Study of the Liver
publisher.none.fl_str_mv Korean Association for the Study of the Liver
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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