title: Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia.
abstract: OBJECTIVE
  Recent evidence suggests that a particular gut microbial community may favour occurrence of the metabolic diseases. Recently, we reported that high-fat (HF) feeding was associated with higher endotoxaemia and lower Bifidobacterium species (spp.) caecal content in mice. We therefore tested whether restoration of the quantity of caecal Bifidobacterium spp. could modulate metabolic endotoxaemia, the inflammatory tone and the development of diabetes.
  
  
  METHODS
  Since bifidobacteria have been reported to reduce intestinal endotoxin levels and improve mucosal barrier function, we specifically increased the gut bifidobacterial content of HF-diet-fed mice through the use of a prebiotic (oligofructose [OFS]).
  
  
  RESULTS
  Compared with normal chow-fed control mice, HF feeding significantly reduced intestinal Gram-negative and Gram-positive bacteria including levels of bifidobacteria, a dominant member of the intestinal microbiota, which is seen as physiologically positive. As expected, HF-OFS-fed mice had totally restored quantities of bifidobacteria. HF-feeding significantly increased endotoxaemia, which was normalised to control levels in HF-OFS-treated mice. Multiple-correlation analyses showed that endotoxaemia significantly and negatively correlated with Bifidobacterium spp., but no relationship was seen between endotoxaemia and any other bacterial group. Finally, in HF-OFS-treated-mice, Bifidobacterium spp. significantly and positively correlated with improved glucose tolerance, glucose-induced insulin secretion and normalised inflammatory tone (decreased endotoxaemia, plasma and adipose tissue proinflammatory cytokines).
  
  
  CONCLUSIONS
  Together, these findings suggest that the gut microbiota contribute towards the pathophysiological regulation of endotoxaemia and set the tone of inflammation for occurrence of diabetes and/or obesity. Thus, it would be useful to develop specific strategies for modifying gut microbiota in favour of bifidobacteria to prevent the deleterious effect of HF-diet-induced metabolic diseases.
authors.affiliation: Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, Université catholique de Louvain, Av. E. Mounier, 73/69, 1200 Brussels, Belgium. patrice.cani@uclouvain.be
authors.forename: P D
authors.initials: PD
authors.lastname: Cani
authors.forename: A M
authors.initials: AM
authors.lastname: Neyrinck
authors.forename: F
authors.initials: F
authors.lastname: Fava
authors.forename: C
authors.initials: C
authors.lastname: Knauf
authors.forename: R G
authors.initials: RG
authors.lastname: Burcelin
authors.forename: K M
authors.initials: KM
authors.lastname: Tuohy
authors.forename: G R
authors.initials: GR
authors.lastname: Gibson
authors.forename: N M
authors.initials: NM
authors.lastname: Delzenne
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology; D000818:Animals; D001644:Bifidobacterium / Q000502:physiology*; D001835:Body Weight; D003920:Diabetes Mellitus / Q000453:epidemiology* / Q000517:prevention & control; D004041:Dietary Fats / Q000009:adverse effects*; D019446:Endotoxemia / Q000503:physiopathology; D004731:Endotoxins / Q000032:analysis; D002149:Energy Intake; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL