Sequential Changes in the Mesenteric Lymph Node Microbiome and Immune Response during Cirrhosis Induction in Rats
Por:
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
Publicada:
1 ene 2019
Resumen:
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.
Filiaciones:
Santiago, A:
Vall dHebron Res Inst, Dept Gastroenterol, Barcelona, Spain
Sanchez, E:
Univ Autonoma Barcelona, Dept Gastroenterol, Hosp Santa Creu & St Pau, Barcelona, Spain
Inst Salud Carlos III, CIBERehd, Madrid, Spain
Clark, A:
Vall dHebron Res Inst, Dept Gastroenterol, Barcelona, Spain
Pozuelo, M:
Vall dHebron Res Inst, Dept Gastroenterol, Barcelona, Spain
Calvo, M:
Vall dHebron Res Inst, Dept Gastroenterol, Barcelona, Spain
Yanez, F:
Vall dHebron Res Inst, Dept Gastroenterol, Barcelona, Spain
Sarrabayrouse, G:
Vall dHebron Res Inst, Dept Gastroenterol, Barcelona, Spain
Perea, L:
Univ Autonoma Barcelona, Dept Immunol, IIB St Pau Res Inst, Hosp Santa Creu & St Pau, Barcelona, Spain
Vidal, S:
Univ Autonoma Barcelona, Dept Immunol, IIB St Pau Res Inst, Hosp Santa Creu & St Pau, Barcelona, Spain
Gallardo, A:
Univ Autonoma Barcelona, Dept Pathol, Hosp Santa Creu & St Pau, Barcelona, Spain
Guarner, C:
Univ Autonoma Barcelona, Dept Gastroenterol, Hosp Santa Creu & St Pau, Barcelona, Spain
Inst Salud Carlos III, CIBERehd, Madrid, Spain
Soriano, G:
Univ Autonoma Barcelona, Dept Gastroenterol, Hosp Santa Creu & St Pau, Barcelona, Spain
Inst Salud Carlos III, CIBERehd, Madrid, Spain
Manichanh, C:
Vall dHebron Res Inst, Dept Gastroenterol, Barcelona, Spain
Inst Salud Carlos III, CIBERehd, Madrid, Spain
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