ena-STUDY-IATA-CSIC-03-12-2014-12:28:39:724-132
Bifidobacterium pseudocatenulatum CECT 7765 reduces obesity-associated inflammation by restoring the lymphocyte-macrophage balance and gut microbiota structure in  high-fat-diet fed mice Bifidobacterium pseudocatenulatum CECT 7765 reduces obesity-associated inflammation by restoring the lymphocyte-macrophage balance and gut microbiota structure in  high-fat-diet fed mice
The role of intestinal dysbiosis in obesity-associated systemic inflammation via the cross-talk with peripheral tissues is under debate. Our objective was to deciphering the mechanisms by which intervention in the gut ecosystem with bifidobacteria could reduce systemic inflammation and improve metabolic derangements in obese high-fat diet (HFD)-fed mice. Adult male wild-type C57BL-6 mice were fed a standard diet or high-fat diet (HFD), supplemented with placebo or Bifidobacterium pseudocatenulatum CECT 7765, for 14 weeks. Lymphocytes, macrophages and cytokine/chemokine concentrations were quantified in blood, gut, liver and adipose tissue using bead-based multiplex assays. Serum biochemical parameters were determined by ELISA and enzymatic assays. Histology was assessed by hematoxylin-eosins staining. Microbiota was analyzed by 16S rRNA gene pyrosequencing and quantitative PCR. B. pseudocatenulatum CECT 7765 reduced obesity-associated systemic inflammation by restoring the balance between regulatory T cells (Tregs) and B lymphocytes and reducing pro-inflammatory cytokines of adaptive (IL-17A) and innate (TNF-a) immunity and endotoxemia. In the gut, the bifidobacterial administration partially restored the HFD-induced microbiota alterations, reducing abundances of LPS-producing Proteobacteria and of Firmicutes, paralleled to reductions in B cells, macrophages, and cytokines (IL-6, MCP-1, TNF-a, IL-17A), which could contribute to systemic effects. In adipose tissue the bifidobacterial administration reduced B cells whereas in liver increased Tregs and shifted different cytokines (TNF-a, MCP-1, ILP-10, IL-6 plus IL-17A in adipose tissue and TNF-a, INF-?, IL-1ß plus IL-17A in liver). In both tissues, the bifidobacteria reduced pro-inflammatory macrophages, TNF-a and IL-17A. These effects were parallel to reduced body weight gain and serum cholesterol, triglyceride, glucose and insulin levels and to improved oral glucose tolerance and insulin sensitivity in obese mice. Herein, we provide clear evidence of the immune cellular mechanisms by which the inflammatory cascade associated with diet-induced obesity is reversed by administration of a specific intestinal bacterium and that the effects were associated with modulation of gut microbiota structure.
The role of intestinal dysbiosis in obesity-associated systemic inflammation via the cross-talk with peripheral tissues is under debate. Our objective was to deciphering the mechanisms by which intervention in the gut ecosystem with bifidobacteria could reduce systemic inflammation and improve metabolic derangements in obese high-fat diet (HFD)-fed mice. Adult male wild-type C57BL-6 mice were fed a standard diet or high-fat diet (HFD), supplemented with placebo or Bifidobacterium pseudocatenulatum CECT 7765, for 14 weeks. Lymphocytes, macrophages and cytokine/chemokine concentrations were quantified in blood, gut, liver and adipose tissue using bead-based multiplex assays. Serum biochemical parameters were determined by ELISA and enzymatic assays. Histology was assessed by hematoxylin-eosins staining. Microbiota was analyzed by 16S rRNA gene pyrosequencing and quantitative PCR. B. pseudocatenulatum CECT 7765 reduced obesity-associated systemic inflammation by restoring the balance between regulatory T cells (Tregs) and B lymphocytes and reducing pro-inflammatory cytokines of adaptive (IL-17A) and innate (TNF-a) immunity and endotoxemia. In the gut, the bifidobacterial administration partially restored the HFD-induced microbiota alterations, reducing abundances of LPS-producing Proteobacteria and of Firmicutes, paralleled to reductions in B cells, macrophages, and cytokines (IL-6, MCP-1, TNF-a, IL-17A), which could contribute to systemic effects. In adipose tissue the bifidobacterial administration reduced B cells whereas in liver increased Tregs and shifted different cytokines (TNF-a, MCP-1, ILP-10, IL-6 plus IL-17A in adipose tissue and TNF-a, INF-?, IL-1ß plus IL-17A in liver). In both tissues, the bifidobacteria reduced pro-inflammatory macrophages, TNF-a and IL-17A. These effects were parallel to reduced body weight gain and serum cholesterol, triglyceride, glucose and insulin levels and to improved oral glucose tolerance and insulin sensitivity in obese mice. Herein, we provide clear evidence of the immune cellular mechanisms by which the inflammatory cascade associated with diet-induced obesity is reversed by administration of a specific intestinal bacterium and that the effects were associated with modulation of gut microbiota structure.