Oligofructose reduces diet-induced metabolic disease in mice
Obesity and metabolic disorders (insulin resistance, hyperlipaemia) are tightly linked to inflammation. Adipose tissue has a high capacity to produce pro-inflammatory cytokines, such as IL-1, IL-6 and TNF-α Such cytokines are known to be involved in insulin resistance, favouring hyperinsulinaemia and excessive hepatic and adipose tissue lipid storage. The triggering factor leading to such metabolic alterations upon high-fat feeding remains to be determined. Recent studies on the mammalian host-gut relationship have demonstrated, however, the importance of the microflora in energy, glucose and lipid metabolism.
The aim of this study was therefore to test whether changes in the intestinal microbiota upon dietary intervention with oligo-fructose may control metabolic disease in mice fed with a high-fat diet. Mice (n=8 per group) were fed four different diets for 14 weeks: a standard diet (control), a high-fat diet (49.5% of total dry weight), a high-fat diet supplemented with oligofructose (10% of Orafti®P95) and a high-fat diet supplemented with a non-prebiotic fibre (10% of cellulose).
The high-fat feeding altered dramatically the microbiota composition by reducing the numbers of dominant Gram-positive groups, e.g. Bifidobacterium spp. and E.rectale-C.coccoides groups, and the murine Gram-negative group, Bacteroides MB, as compared with the standard diet group (P<0.05 for all). However, it did not affect total bacterial numbers. The numbers of E.rectale-C.coccoides groups were even more reduced in the (high-fat) cellulose group (P<0.05 vs. high-fat group). Oligofructose supplementation totally restored the quantities of bifidobacteria (P<0.05 for all). Significantly higher levels of endotoxaemia were measured in high-fat and (high-fat) cellulose groups (P<0.05 vs. standard and oligo-fructose groups). Oligofructose, on the other hand, lowered endotoxaemia to control values. This suggests that the increase in bifidobacteria induced by the prebiotic protected against high-fat induced endotoxaemia. Multiple correlation analyses showed that endotoxaemia was significantly and negatively correlated with Bifidobacterium spp., but no relationship was seen between any other bacterial groups.
Furthermore, mice in the oligo-fructose group had improved glucose tolerance (area under the curve), glucose-induced insulin secretion, as well as lower fasting insulinaemia (vs. high fat and (high fat) cellulose groups, P<0.05 for both). No differences were observed for the cellulose vs. high fat groups. These data suggest that the specific increase in bifidobacteria and subsequent lower level of endotoxaemia upon oligofructose feeding had a beneficial impact on glucose homeostasis.
Moreover, body weight gain as well as visceral, epididymal and subcutaneous adipose tissue weight were significantly lower in the oligofructose and cellulose groups as compared to the high-fat group (P<0.05). And, the oligofructose group had 20% lower subcutaneous adipose tissue than the cellulose group. Body weight and visceral fat mass correlated positively with endotoxin plasma levels and negatively with bifidobacteria levels (for the oligofructose group).
In addition, a normalisation of IL-1α and IL-6 cytokines was observed upon oligofructose feeding (vs. high-fat diet). Adipose tissue mRNA concentrations of IL-1, TNF-α and plasminogen activator inhibitor type-1 (Pai-1, or Serpine-1) were increased in high-fat and high-fat cellulose groups, whereas these were blunted with oligo-fructose feeding. These results indicate that a lower fat mass and body weight (as seen with cellulose) are not sufficient for a lower inflammatory tone and that such effect is specific for prebiotic supplementation. Here again, plasma cytokines were positively correlated with plasma endotoxin levels and negatively with bifidobacteria levels.
To conclude, it appears that the gut microbiota contribute to the patho-physiological regulation of endotoxaemia, the tone of inflammation and the occurrence of diabetes and obesity. Therefore, modifying selectively the gut microbiota in favour of bifidobacteria by the use of prebiotics such as oligofructose may reduce diet-induced metabolic disease.
Cani PD, Neyrinck AM, Fava F, Knauf C, Burcelin RG, Tuohy KM, Gibson GR, Delzenne NM. (2007) Selective increases of bifidobacteria in gut microflora improve high-fat-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologica 50: 2374-2383.
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