Bifidobacterium pseudocatenulatum CECT 7765 Reduces Obesity-Associated Inflammation by Restoring the Lymphocyte-Macrophage Balance and Gut Microbiota Structure in High-Fat Diet-Fed Mice

Abstract

Background/ObjectivesThe role of intestinal dysbiosis in obesity-associated systemic inflammation via the cross-talk with peripheral tissues is under debate. Our objective was to decipher the mechanisms by which intervention in the gut ecosystem with a specific Bifidobacterium strain reduces systemic inflammation and improves metabolic dysfunction in obese high-fat diet (HFD) fed mice.MethodsAdult male wild-type C57BL-6 mice were fed either a standard or 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. Biochemical parameters in serum were determined by ELISA and enzymatic assays. Histology was assessed by hematoxylin-eosin staining. Microbiota was analyzed by 16S rRNA gene pyrosequencing and quantitative PCR.Results 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-α) immunity and endotoxemia. In the gut, the bifidobacterial administration partially restored the HFD-induced alterations in microbiota, reducing abundances of Firmicutes and of LPS-producing Proteobacteria, paralleled to reductions in B cells, macrophages, and cytokines (IL-6, MCP-1, TNF-α, IL-17A), which could contribute to systemic effects. In adipose tissue, bifidobacterial administration reduced B cells whereas in liver the treatment increased Tregs and shifted different cytokines (MCP-1 plus ILP-10 in adipose tissue and INF-γ plus IL-1β in liver). In both tissues, the bifidobacteria reduced pro-inflammatory macrophages and, TNF-α and IL-17A concentrations. These effects were accompanied by reductions in body weight gain and in serum cholesterol, triglyceride, glucose and insulin levels and improved oral glucose tolerance and insulin sensitivity in obese mice.ConclusionsHere, we provide evidence of the immune cellular mechanisms by which the inflammatory cascade associated with diet-induced obesity is attenuated by the administration of a specific Bifidobacterium strain and that these effects are associated with modulation of gut microbiota structure.

Childhood BMI in relation to microbiota in infancy and lifetime antibiotic use

“…The mechanism is at least partly related to the amelioration of the diet-induced endotoxemia and inflammation in the gut, liver, and in adipose tissue [45, 50, 51], and the deconjugation of bile acids [52], which influences the host’s lipid metabolism and energy expenditure [23]. B. pseudocatenulatum has been shown to cause changes in the expression of hepatic genes involved in lipid metabolism [53].…”

Microbiota in obesity: interactions with enteroendocrine, immune and central nervous systems

“…Because the microbiota is rapidly altered by diet and the consumption of a HFD is known to cause obesity , it has been suggested that diet‐induced alterations in microbiota could contribute to the pathogenesis of obesity. To identify potentially beneficial and detrimental bacteria for obesity development, we review the HFD‐induced effects on common parameters related to obesity and on the rodent microbiota . A number of significant correlations between the human or rodent microbiota and several common parameters related to obesity have been reported (Table ) .…”

T cell epitope redundancy: cross-conservation of the TCR face between pathogens and self and its implications for vaccines and autoimmunity

“…However, the complexity of the human microbiome may make it difficult to deconvolute the many cross-reactive peptides that could be driving this link. Associations between specific gut microbes and disease [100] may make it possible to narrow down the possibilities, although it seems unlikely that a single gut microbe will be the culprit.…”