Alleviation of high fat diet-induced obesity by oligofructose in gnotobiotic mice is independent of presence of Bifidobacterium longum

Abstract

Scope: Diet-induced obesity is associated with changes in the gut microbiota and low-grade inflammation. Oligofructose was reported to ameliorate high fat diet-induced metabolic disorders in mice by restoring the number of intestinal bifidobacteria. However, this has not been experimentally demonstrated.

Methods and results: We fed conventional mice, germfree mice, mice associated with a simplified human gut microbiota composed of eight bacterial species including Bifidobacterium longum (SIHUMI), and mice associated with SIHUMI without B. longum a low fat diet (LFD), a high fat diet (HFD), or a HFD containing 10% oligofructose (HFD + OFS) for five weeks. We assessed body composition, bacterial cell numbers and metabolites, markers of inflammation, and gut permeability. Conventional mice fed HFD or HFD + OFS did not differ in body weight gain and glucose tolerance. The gnotobiotic mouse groups fed LFD or HFD + OFS gained less body weight and body fat, and displayed an improved glucose tolerance compared with mice fed HFD. These differences were not affected by the presence of B. longum. Mice fed HFD showed no signs of inflammation or increased intestinal permeability.

Conclusion: The ability of oligofructose to reduce obesity and to improve glucose tolerance in gnotobiotic mice fed HFD was independent of the presence of B. longum.

Keywords: Bifidobacterium longum; Diet-induced obesity; Glucose tolerance; Metabolic endotoxemia; Oligofructose.

Figure 1

Weight gain and glucose tolerance of conventional mice. Weight gain (A), oral glucose tolerance (B), and total area under the curve (AUC) (C) of conventional C3H mice after five weeks on semisynthetic diets: low fat diet (○ LFD), high fat diet (□ HFD), and high fat diet supplemented with oligofructose (∆HFD + OFS). Data of weight gain and AUC during glucose tolerance test are expressed as medians. Boxes show the 25–75, whiskers the 5–95 percentile (*p < 0.05, **p < 0.01). Plasma glucose data are expressed as means with their standard errors (*p < 0.05, LFD versus HFD + OFS). n = 5–7 per dietary group.

Figure 2

Body weight gain and weight of epididymal white adipose tissue (eWAT). (A) Germfree, (B) SIHUMI, and (C) SIHUMI‐Bif mice either fed a semisynthetic low fat diet (LFD), high fat diet (HFD), or high fat diet supplemented with oligofructose (HFD + OFS). Data are expressed as medians. Boxes show the 25–75, whiskers the 5–95 percentile (*p < 0.05, **p < 0.01, ***p < 0.001). n = 5–7 per dietary group.

Figure 3

Glucose tolerance test in gnotobiotic mice. Plasma glucose (mmol/L) following an oral glucose load (2 g/kg body weight, 200 g/L glucose) in germfree (A), SIHUMI (B), and SIHUMI‐Bif mice (C) fed one of these semisynthetic diets: low fat diet (○ LFD), high fat diet (□ HFD), and high fat diet supplemented with oligofructose (∆ HFD + OFS). Plasma glucose data are expressed as means with their standard errors (*p < 0.05, **p < 0.01, ***p < 0.001, LFD versus HFD; ^## p < 0.01, LFD versus HFD + OFS; ⁺ p < 0.05, ⁺⁺ p < 0.01, HFD versus HFD + OFS). Box plots represent the total area under the curve (AUC) for each dataset. Data are expressed as medians. Boxes show the 25–75, whiskers the 5–95 percentile (**p < 0.01, ***p < 0.001). n = 5–7 per dietary group, except for germfree mice fed OFS (n = 4).

Figure 4

Systemic FITC‐dextran concentration and relative mRNA expression of jejuna epithelial tight‐junction proteins zonula occludens 1 (Zo1) and occludin (Ocln). (A) Germfree, (B) SIHUMI, and (C) SIHUMI‐Bif mice either fed a semisynthetic low fat diet (LFD), high fat diet (HFD), or high fat diet supplemented with oligofructose (HFD + OFS). Data are expressed as medians. Boxes show the 25–75, whiskers the 5–95 percentile (*p < 0.05, **p < 0.01) n = 6–7 per dietary group.

Figure 5

Relative mRNA expression of Toll‐like receptor 4 (Tlr4) and proinflammatory cytokines tumor necrosis factor alpha (Tnfa) and interleukin‐1 beta (Il1b) in liver. (A) Germfree, (B) SIHUMI, and (C) SIHUMI‐Bif. Mice were either fed a semisynthetic low fat diet (LFD), high fat diet (HFD), or high fat diet supplemented with oligofructose (HFD + OFS). Data are expressed as medians. Boxes show the 25–75, whiskers the 5–95 percentile (*p < 0.05, **p < 0.01). n = 6–7 per dietary group.