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

ABSTRACT 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 tetrachlo...

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Autores principales:	Alba Santiago, Elisabet Sanchez, Allison Clark, Marta Pozuelo, Miguel Calvo, Francisca Yañez, Guillaume Sarrabayrouse, Lidia Perea, Silvia Vidal, Alberto Gallardo, Carlos Guarner, German Soriano, Chaysavanh Manichanh
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	cirrhosis complication bacterial translocation decompensated cirrhosis proinflammatory response Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/83c4800beea447f29a6182eb6644c663
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spelling	oai:doaj.org-article:83c4800beea447f29a6182eb6644c6632021-12-02T19:47:34ZSequential Changes in the Mesenteric Lymph Node Microbiome and Immune Response during Cirrhosis Induction in Rats10.1128/mSystems.00278-182379-5077https://doaj.org/article/83c4800beea447f29a6182eb6644c6632019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00278-18https://doaj.org/toc/2379-5077ABSTRACT 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-liver-immunity 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.Alba SantiagoElisabet SanchezAllison ClarkMarta PozueloMiguel CalvoFrancisca YañezGuillaume SarrabayrouseLidia PereaSilvia VidalAlberto GallardoCarlos GuarnerGerman SorianoChaysavanh ManichanhAmerican Society for Microbiologyarticlecirrhosis complicationbacterial translocationdecompensated cirrhosisproinflammatory responseMicrobiologyQR1-502ENmSystems, Vol 4, Iss 1 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	cirrhosis complication bacterial translocation decompensated cirrhosis proinflammatory response Microbiology QR1-502
spellingShingle	cirrhosis complication bacterial translocation decompensated cirrhosis proinflammatory response Microbiology QR1-502 Alba Santiago Elisabet Sanchez Allison Clark Marta Pozuelo Miguel Calvo Francisca Yañez Guillaume Sarrabayrouse Lidia Perea Silvia Vidal Alberto Gallardo Carlos Guarner German Soriano Chaysavanh Manichanh Sequential Changes in the Mesenteric Lymph Node Microbiome and Immune Response during Cirrhosis Induction in Rats
description	ABSTRACT 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-liver-immunity 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.
format	article
author	Alba Santiago Elisabet Sanchez Allison Clark Marta Pozuelo Miguel Calvo Francisca Yañez Guillaume Sarrabayrouse Lidia Perea Silvia Vidal Alberto Gallardo Carlos Guarner German Soriano Chaysavanh Manichanh
author_facet	Alba Santiago Elisabet Sanchez Allison Clark Marta Pozuelo Miguel Calvo Francisca Yañez Guillaume Sarrabayrouse Lidia Perea Silvia Vidal Alberto Gallardo Carlos Guarner German Soriano Chaysavanh Manichanh
author_sort	Alba Santiago
title	Sequential Changes in the Mesenteric Lymph Node Microbiome and Immune Response during Cirrhosis Induction in Rats
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
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/83c4800beea447f29a6182eb6644c663
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Sequential Changes in the Mesenteric Lymph Node Microbiome and Immune Response during Cirrhosis Induction in Rats

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