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Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice.

Everard A, Lazarevic V, Derrien M, Girard M, Muccioli GG, Muccioli GM, Neyrinck AM, Possemiers S, Van Holle A, François P, de Vos WM, Delzenne NM, Schrenzel J, Cani PD - Diabetes (2011)

Bottom Line: Metabolic parameters, gene expression, glucose homeostasis, and enteroendocrine-related L-cell function were documented in both models.In addition, prebiotics improved glucose tolerance, increased L-cell number and associated parameters (intestinal proglucagon mRNA expression and plasma glucagon-like peptide-1 levels), and reduced fat-mass development, oxidative stress, and low-grade inflammation.We conclude that specific gut microbiota modulation improves glucose homeostasis, leptin sensitivity, and target enteroendocrine cell activity in obese and diabetic mice.

View Article: PubMed Central - PubMed

Affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.

ABSTRACT

Objective: To investigate deep and comprehensive analysis of gut microbial communities and biological parameters after prebiotic administration in obese and diabetic mice.

Research design and methods: Genetic (ob/ob) or diet-induced obese and diabetic mice were chronically fed with prebiotic-enriched diet or with a control diet. Extensive gut microbiota analyses, including quantitative PCR, pyrosequencing of the 16S rRNA, and phylogenetic microarrays, were performed in ob/ob mice. The impact of gut microbiota modulation on leptin sensitivity was investigated in diet-induced leptin-resistant mice. Metabolic parameters, gene expression, glucose homeostasis, and enteroendocrine-related L-cell function were documented in both models.

Results: In ob/ob mice, prebiotic feeding decreased Firmicutes and increased Bacteroidetes phyla, but also changed 102 distinct taxa, 16 of which displayed a >10-fold change in abundance. In addition, prebiotics improved glucose tolerance, increased L-cell number and associated parameters (intestinal proglucagon mRNA expression and plasma glucagon-like peptide-1 levels), and reduced fat-mass development, oxidative stress, and low-grade inflammation. In high fat-fed mice, prebiotic treatment improved leptin sensitivity as well as metabolic parameters.

Conclusions: We conclude that specific gut microbiota modulation improves glucose homeostasis, leptin sensitivity, and target enteroendocrine cell activity in obese and diabetic mice. By profiling the gut microbiota, we identified a catalog of putative bacterial targets that may affect host metabolism in obesity and diabetes.

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Related in: MedlinePlus

Analysis of the gut bacterial community by 16S rRNA pyrosequencing from obese mice on standard chow and prebiotic diets. A: Percentage of each community contributed by the indicated phyla. B: Clustering of mice cecal microbial communities in the two tested groups based on the unweighted UniFrac analysis and 97% ID phylotypes or (C) 100% ID phylotypes. Red corresponds to the standard chow diet (Ob-CT), and blue corresponds to the prebiotic diet (Ob-Pre). Branch length represents distance between environments in UniFrac units, indicated by the scale bar. D: Relative abundance of different phyla expressed as the percentage of total sequence reads. Mean ± SEM. n = 10 mice/group. *P < 0.05; #P < 0.1, determined by a two-tailed Student t test. PCoA based on the unweighted (presence/absence) UniFrac analysis and (E) 97% ID phylotypes or (G) 100% ID phylotypes. Each circle representing a single sample is colored according to the dietary conditions; red corresponds to Ob-CT and blue corresponds to Ob-Pre. F: Number of 97% ID phylotypes shared among a given number of mice (middle panel) and their corresponding abundance expressed as the percentage of total reads (top panel) indicated by blue bars. Cumulative data are indicated in gray. The bottom panel shows the relative abundance of 97% ID phylotypes, in which the x-axis indicates individual phylotypes ranked according to their relative abundance from high to low, and the y-axis indicates the cumulative abundance (the percentage of total reads). Gray triangles correspond to a pooled data set from 20 mice.
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Figure 1: Analysis of the gut bacterial community by 16S rRNA pyrosequencing from obese mice on standard chow and prebiotic diets. A: Percentage of each community contributed by the indicated phyla. B: Clustering of mice cecal microbial communities in the two tested groups based on the unweighted UniFrac analysis and 97% ID phylotypes or (C) 100% ID phylotypes. Red corresponds to the standard chow diet (Ob-CT), and blue corresponds to the prebiotic diet (Ob-Pre). Branch length represents distance between environments in UniFrac units, indicated by the scale bar. D: Relative abundance of different phyla expressed as the percentage of total sequence reads. Mean ± SEM. n = 10 mice/group. *P < 0.05; #P < 0.1, determined by a two-tailed Student t test. PCoA based on the unweighted (presence/absence) UniFrac analysis and (E) 97% ID phylotypes or (G) 100% ID phylotypes. Each circle representing a single sample is colored according to the dietary conditions; red corresponds to Ob-CT and blue corresponds to Ob-Pre. F: Number of 97% ID phylotypes shared among a given number of mice (middle panel) and their corresponding abundance expressed as the percentage of total reads (top panel) indicated by blue bars. Cumulative data are indicated in gray. The bottom panel shows the relative abundance of 97% ID phylotypes, in which the x-axis indicates individual phylotypes ranked according to their relative abundance from high to low, and the y-axis indicates the cumulative abundance (the percentage of total reads). Gray triangles correspond to a pooled data set from 20 mice.

Mentions: We observed a significant phylum-wide shift between Bacteroidetes and Firmicutes, of which the abundance increased and decreased, respectively, after the prebiotic treatment, compared with the control (Fig. 1A and D). The abundance of Actinobacteria and Proteobacteria tended to increase in the prebiotic group (P = 0.07 and P = 0.051, respectively) (Fig. 1D).


Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice.

Everard A, Lazarevic V, Derrien M, Girard M, Muccioli GG, Muccioli GM, Neyrinck AM, Possemiers S, Van Holle A, François P, de Vos WM, Delzenne NM, Schrenzel J, Cani PD - Diabetes (2011)

Analysis of the gut bacterial community by 16S rRNA pyrosequencing from obese mice on standard chow and prebiotic diets. A: Percentage of each community contributed by the indicated phyla. B: Clustering of mice cecal microbial communities in the two tested groups based on the unweighted UniFrac analysis and 97% ID phylotypes or (C) 100% ID phylotypes. Red corresponds to the standard chow diet (Ob-CT), and blue corresponds to the prebiotic diet (Ob-Pre). Branch length represents distance between environments in UniFrac units, indicated by the scale bar. D: Relative abundance of different phyla expressed as the percentage of total sequence reads. Mean ± SEM. n = 10 mice/group. *P < 0.05; #P < 0.1, determined by a two-tailed Student t test. PCoA based on the unweighted (presence/absence) UniFrac analysis and (E) 97% ID phylotypes or (G) 100% ID phylotypes. Each circle representing a single sample is colored according to the dietary conditions; red corresponds to Ob-CT and blue corresponds to Ob-Pre. F: Number of 97% ID phylotypes shared among a given number of mice (middle panel) and their corresponding abundance expressed as the percentage of total reads (top panel) indicated by blue bars. Cumulative data are indicated in gray. The bottom panel shows the relative abundance of 97% ID phylotypes, in which the x-axis indicates individual phylotypes ranked according to their relative abundance from high to low, and the y-axis indicates the cumulative abundance (the percentage of total reads). Gray triangles correspond to a pooled data set from 20 mice.
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Figure 1: Analysis of the gut bacterial community by 16S rRNA pyrosequencing from obese mice on standard chow and prebiotic diets. A: Percentage of each community contributed by the indicated phyla. B: Clustering of mice cecal microbial communities in the two tested groups based on the unweighted UniFrac analysis and 97% ID phylotypes or (C) 100% ID phylotypes. Red corresponds to the standard chow diet (Ob-CT), and blue corresponds to the prebiotic diet (Ob-Pre). Branch length represents distance between environments in UniFrac units, indicated by the scale bar. D: Relative abundance of different phyla expressed as the percentage of total sequence reads. Mean ± SEM. n = 10 mice/group. *P < 0.05; #P < 0.1, determined by a two-tailed Student t test. PCoA based on the unweighted (presence/absence) UniFrac analysis and (E) 97% ID phylotypes or (G) 100% ID phylotypes. Each circle representing a single sample is colored according to the dietary conditions; red corresponds to Ob-CT and blue corresponds to Ob-Pre. F: Number of 97% ID phylotypes shared among a given number of mice (middle panel) and their corresponding abundance expressed as the percentage of total reads (top panel) indicated by blue bars. Cumulative data are indicated in gray. The bottom panel shows the relative abundance of 97% ID phylotypes, in which the x-axis indicates individual phylotypes ranked according to their relative abundance from high to low, and the y-axis indicates the cumulative abundance (the percentage of total reads). Gray triangles correspond to a pooled data set from 20 mice.
Mentions: We observed a significant phylum-wide shift between Bacteroidetes and Firmicutes, of which the abundance increased and decreased, respectively, after the prebiotic treatment, compared with the control (Fig. 1A and D). The abundance of Actinobacteria and Proteobacteria tended to increase in the prebiotic group (P = 0.07 and P = 0.051, respectively) (Fig. 1D).

Bottom Line: Metabolic parameters, gene expression, glucose homeostasis, and enteroendocrine-related L-cell function were documented in both models.In addition, prebiotics improved glucose tolerance, increased L-cell number and associated parameters (intestinal proglucagon mRNA expression and plasma glucagon-like peptide-1 levels), and reduced fat-mass development, oxidative stress, and low-grade inflammation.We conclude that specific gut microbiota modulation improves glucose homeostasis, leptin sensitivity, and target enteroendocrine cell activity in obese and diabetic mice.

View Article: PubMed Central - PubMed

Affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.

ABSTRACT

Objective: To investigate deep and comprehensive analysis of gut microbial communities and biological parameters after prebiotic administration in obese and diabetic mice.

Research design and methods: Genetic (ob/ob) or diet-induced obese and diabetic mice were chronically fed with prebiotic-enriched diet or with a control diet. Extensive gut microbiota analyses, including quantitative PCR, pyrosequencing of the 16S rRNA, and phylogenetic microarrays, were performed in ob/ob mice. The impact of gut microbiota modulation on leptin sensitivity was investigated in diet-induced leptin-resistant mice. Metabolic parameters, gene expression, glucose homeostasis, and enteroendocrine-related L-cell function were documented in both models.

Results: In ob/ob mice, prebiotic feeding decreased Firmicutes and increased Bacteroidetes phyla, but also changed 102 distinct taxa, 16 of which displayed a >10-fold change in abundance. In addition, prebiotics improved glucose tolerance, increased L-cell number and associated parameters (intestinal proglucagon mRNA expression and plasma glucagon-like peptide-1 levels), and reduced fat-mass development, oxidative stress, and low-grade inflammation. In high fat-fed mice, prebiotic treatment improved leptin sensitivity as well as metabolic parameters.

Conclusions: We conclude that specific gut microbiota modulation improves glucose homeostasis, leptin sensitivity, and target enteroendocrine cell activity in obese and diabetic mice. By profiling the gut microbiota, we identified a catalog of putative bacterial targets that may affect host metabolism in obesity and diabetes.

Show MeSH
Related in: MedlinePlus