Sequential Changes in the Mesenteric Lymph Node Microbiome and Immune Response during Cirrhosis Induction in Rats

Whether the interaction between the gut microbiota and the immune response influences the evolution of cirrhosis is poorly understood. We aimed to investigate modifications of the microbiome and the immune response during the progression of cirrhosis. Rats were treated with carbon tetrachloride (CCl...

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Autores: Santiago, A, Sanchez, E, Clark, A, Pozuelo, M, Calvo, M, Yanez, F, Sarrabayrouse, G, Perea, L, Vidal, S, Gallardo, A, Guarner, C, Soriano, G, Manichanh, C
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p11789
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11789
http://ddd.uab.cat/record/226362
Access Level:acceso abierto
Palabra clave:cirrhosis complication
bacterial translocation
decompensated cirrhosis
proinflammatory response
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spelling Sequential Changes in the Mesenteric Lymph Node Microbiome and Immune Response during Cirrhosis Induction in RatsSantiago, ASanchez, EClark, APozuelo, MCalvo, MYanez, FSarrabayrouse, GPerea, LVidal, SGallardo, AGuarner, CSoriano, GManichanh, Ccirrhosis complicationbacterial translocationdecompensated cirrhosisproinflammatory responseWhether the interaction between the gut microbiota and the immune response influences the evolution of cirrhosis is poorly understood. We aimed to investigate modifications of the microbiome and the immune response during the progression of cirrhosis. Rats were treated with carbon tetrachloride (CCl4) to induce cirrhosis. We then assessed microbiome load and composition in stool, ileocecal contents (ICCs), mesenteric lymph nodes (MLNs), blood, and ascitic fluids (AFs) at 6, 8, and 10 weeks or ascites production and measured cytokine production in MLNs and blood. The microbiome of MLN, blood, and AF showed a distinct composition compared to that of stool and ICCs. Betaproteobacteria (Sutterella) were found associated with the appearance of a decompensated state of cirrhosis. Microbial load increased and showed a positive correlation with the relative abundance of pathobionts in the MLN of decompensated rats. Among several genera, Escherichia and "Candidatus Arthromitus" positively correlated with elevated levels of systemic proinflammatory cytokines. "Candidatus Arthromitus," a segmented filamentous bacteria, was detected in ICC, MLN, and AF samples, suggesting a possible translocation from the gut to the AF through the lymphatic system, whereas Escherichia was detected in ICC, MLN, AF, and blood, suggesting a possible translocation from the gut to the AF through the bloodstream. In the present study, we demonstrate that microbiome changes in distinct intestinal sites are associated with microbial shifts in the MLNs as well as an increase in cytokine production, providing further evidence of the role the gut-liverimmunity axis plays in the progression of cirrhosis. IMPORTANCE Cirrhosis severity in patients was previously shown to be associated with progressive changes in the fecal microbiome in a longitudinal setting. Recent evidence shows that bacterial translocation from the gut to the extraintestinal sites could play a major role in poor disease outcome and patient survival. However, the underlying mechanisms involving the microbiota in the disease progression are not well understood. Here, using an animal model of cirrhosis in a longitudinal and multibody sites setting, we showed the presence of a distinct composition of the microbiome in mesenteric lymph nodes, blood, and ascitic fluid compared to that in feces and ileocecal content, suggesting compartmentalization of the gut microbiome. We also demonstrate that microbiome changes in intestinal sites are associated with shifts in specific microbial groups in the mesenteric lymph nodes as well as an increase in systemic cytokine production, linking inflammation to decompensated cirrhosis in the gut-liver-immunity axis.AMER SOC MICROBIOLOGY2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11789http://ddd.uab.cat/record/226362mSystemsISSN: 23795077reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p117892026-06-14T12:41:47Z
dc.title.none.fl_str_mv Sequential Changes in the Mesenteric Lymph Node Microbiome and Immune Response during Cirrhosis Induction in Rats
title Sequential Changes in the Mesenteric Lymph Node Microbiome and Immune Response during Cirrhosis Induction in Rats
spellingShingle Sequential Changes in the Mesenteric Lymph Node Microbiome and Immune Response during Cirrhosis Induction in Rats
Santiago, A
cirrhosis complication
bacterial translocation
decompensated cirrhosis
proinflammatory response
title_short Sequential Changes in the Mesenteric Lymph Node Microbiome and Immune Response during Cirrhosis Induction in Rats
title_full Sequential Changes in the Mesenteric Lymph Node Microbiome and Immune Response during Cirrhosis Induction in Rats
title_fullStr Sequential Changes in the Mesenteric Lymph Node Microbiome and Immune Response during Cirrhosis Induction in Rats
title_full_unstemmed Sequential Changes in the Mesenteric Lymph Node Microbiome and Immune Response during Cirrhosis Induction in Rats
title_sort Sequential Changes in the Mesenteric Lymph Node Microbiome and Immune Response during Cirrhosis Induction in Rats
dc.creator.none.fl_str_mv Santiago, A
Sanchez, E
Clark, A
Pozuelo, M
Calvo, M
Yanez, F
Sarrabayrouse, G
Perea, L
Vidal, S
Gallardo, A
Guarner, C
Soriano, G
Manichanh, C
author Santiago, A
author_facet Santiago, A
Sanchez, E
Clark, A
Pozuelo, M
Calvo, M
Yanez, F
Sarrabayrouse, G
Perea, L
Vidal, S
Gallardo, A
Guarner, C
Soriano, G
Manichanh, C
author_role author
author2 Sanchez, E
Clark, A
Pozuelo, M
Calvo, M
Yanez, F
Sarrabayrouse, G
Perea, L
Vidal, S
Gallardo, A
Guarner, C
Soriano, G
Manichanh, C
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv cirrhosis complication
bacterial translocation
decompensated cirrhosis
proinflammatory response
topic cirrhosis complication
bacterial translocation
decompensated cirrhosis
proinflammatory response
description Whether the interaction between the gut microbiota and the immune response influences the evolution of cirrhosis is poorly understood. We aimed to investigate modifications of the microbiome and the immune response during the progression of cirrhosis. Rats were treated with carbon tetrachloride (CCl4) to induce cirrhosis. We then assessed microbiome load and composition in stool, ileocecal contents (ICCs), mesenteric lymph nodes (MLNs), blood, and ascitic fluids (AFs) at 6, 8, and 10 weeks or ascites production and measured cytokine production in MLNs and blood. The microbiome of MLN, blood, and AF showed a distinct composition compared to that of stool and ICCs. Betaproteobacteria (Sutterella) were found associated with the appearance of a decompensated state of cirrhosis. Microbial load increased and showed a positive correlation with the relative abundance of pathobionts in the MLN of decompensated rats. Among several genera, Escherichia and "Candidatus Arthromitus" positively correlated with elevated levels of systemic proinflammatory cytokines. "Candidatus Arthromitus," a segmented filamentous bacteria, was detected in ICC, MLN, and AF samples, suggesting a possible translocation from the gut to the AF through the lymphatic system, whereas Escherichia was detected in ICC, MLN, AF, and blood, suggesting a possible translocation from the gut to the AF through the bloodstream. In the present study, we demonstrate that microbiome changes in distinct intestinal sites are associated with microbial shifts in the MLNs as well as an increase in cytokine production, providing further evidence of the role the gut-liverimmunity axis plays in the progression of cirrhosis. IMPORTANCE Cirrhosis severity in patients was previously shown to be associated with progressive changes in the fecal microbiome in a longitudinal setting. Recent evidence shows that bacterial translocation from the gut to the extraintestinal sites could play a major role in poor disease outcome and patient survival. However, the underlying mechanisms involving the microbiota in the disease progression are not well understood. Here, using an animal model of cirrhosis in a longitudinal and multibody sites setting, we showed the presence of a distinct composition of the microbiome in mesenteric lymph nodes, blood, and ascitic fluid compared to that in feces and ileocecal content, suggesting compartmentalization of the gut microbiome. We also demonstrate that microbiome changes in intestinal sites are associated with shifts in specific microbial groups in the mesenteric lymph nodes as well as an increase in systemic cytokine production, linking inflammation to decompensated cirrhosis in the gut-liver-immunity axis.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11789
http://ddd.uab.cat/record/226362
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11789
http://ddd.uab.cat/record/226362
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv AMER SOC MICROBIOLOGY
publisher.none.fl_str_mv AMER SOC MICROBIOLOGY
dc.source.none.fl_str_mv mSystems
ISSN: 23795077
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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