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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

Phylogenetic microarray analysis of gut bacterial community from the Ob-CT and the Ob-Pre mice. A: Clustering of the MITChip phylogenetic fingerprints of the gut microbiota from the cecal content of the Ob-CT and the Ob-Pre mice (n = 10/group). The highest phylogenetic level of specificity of probes (level 1) is depicted on the right. B: Percentage of each community contributed by the indicated taxa. C: Relative abundance of different taxa expressed as the percentage of total sequence reads. Mean ± SEM. n = 10 mice/group. *P < 0.05, determined by a two-tailed Student t test.
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Figure 2: Phylogenetic microarray analysis of gut bacterial community from the Ob-CT and the Ob-Pre mice. A: Clustering of the MITChip phylogenetic fingerprints of the gut microbiota from the cecal content of the Ob-CT and the Ob-Pre mice (n = 10/group). The highest phylogenetic level of specificity of probes (level 1) is depicted on the right. B: Percentage of each community contributed by the indicated taxa. C: Relative abundance of different taxa expressed as the percentage of total sequence reads. Mean ± SEM. n = 10 mice/group. *P < 0.05, determined by a two-tailed Student t test.

Mentions: We also performed gut microbiota analysis using a high-throughput phylogenetic microarray, called MITChip (23,32), and previously compared with 454 pyrosequencing (23,33). The profiles of the cecal microbiota were obtained based on the intensity of 3,580 distinct oligonucleotide probes. The profiles visualized the presence or absence of all targeted operational taxonomic units. Hierarchical clustering analyses of the MITChip phylogenetic fingerprints showed separate clusters between the two treatment groups (Fig. 2A). A Monte Carlo permutation procedure indicated that the overall microbiota detected by MITChip of the control mice was significantly different from that of the prebiotic-treated mice (P = 0.002). Similar to the results obtained by pyrosequencing analysis, we observed a lower relative and absolute abundance of Firmicutes and a higher abundance of Bacteroidetes in the Ob-Pre group compared with the Ob-CT group (Fig. 2B and C). In contrast, the abundance of Actinobacteria was not significantly affected. In addition, a significant decrease in the abundance of Proteobacteria and the class Deltaproteobacteria was observed after the prebiotic treatment (Fig. 2C). Interestingly, the abundance of Verrucomicrobia dramatically increased in the Ob-Pre mice (Fig. 2C). Although the absolute abundance was still low, this increase was, on average, >80-fold higher than in the control mice (Table 2). Importantly, the specific species responsible for the increased abundance of Verrucomicrobia was identified as Akkermansia muciniphila (Table 2). In accordance with the pyrosequencing analysis, the different hierarchical clustering analyses and PCoA showed separate clusters corresponding to the dietary treatment (data not shown). In addition to specific changes observed in the pyrosequencing analyses, we found several previously unidentified modifications at level 2 (Table 2).


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)

Phylogenetic microarray analysis of gut bacterial community from the Ob-CT and the Ob-Pre mice. A: Clustering of the MITChip phylogenetic fingerprints of the gut microbiota from the cecal content of the Ob-CT and the Ob-Pre mice (n = 10/group). The highest phylogenetic level of specificity of probes (level 1) is depicted on the right. B: Percentage of each community contributed by the indicated taxa. C: Relative abundance of different taxa expressed as the percentage of total sequence reads. Mean ± SEM. n = 10 mice/group. *P < 0.05, determined by a two-tailed Student t test.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198091&req=5

Figure 2: Phylogenetic microarray analysis of gut bacterial community from the Ob-CT and the Ob-Pre mice. A: Clustering of the MITChip phylogenetic fingerprints of the gut microbiota from the cecal content of the Ob-CT and the Ob-Pre mice (n = 10/group). The highest phylogenetic level of specificity of probes (level 1) is depicted on the right. B: Percentage of each community contributed by the indicated taxa. C: Relative abundance of different taxa expressed as the percentage of total sequence reads. Mean ± SEM. n = 10 mice/group. *P < 0.05, determined by a two-tailed Student t test.
Mentions: We also performed gut microbiota analysis using a high-throughput phylogenetic microarray, called MITChip (23,32), and previously compared with 454 pyrosequencing (23,33). The profiles of the cecal microbiota were obtained based on the intensity of 3,580 distinct oligonucleotide probes. The profiles visualized the presence or absence of all targeted operational taxonomic units. Hierarchical clustering analyses of the MITChip phylogenetic fingerprints showed separate clusters between the two treatment groups (Fig. 2A). A Monte Carlo permutation procedure indicated that the overall microbiota detected by MITChip of the control mice was significantly different from that of the prebiotic-treated mice (P = 0.002). Similar to the results obtained by pyrosequencing analysis, we observed a lower relative and absolute abundance of Firmicutes and a higher abundance of Bacteroidetes in the Ob-Pre group compared with the Ob-CT group (Fig. 2B and C). In contrast, the abundance of Actinobacteria was not significantly affected. In addition, a significant decrease in the abundance of Proteobacteria and the class Deltaproteobacteria was observed after the prebiotic treatment (Fig. 2C). Interestingly, the abundance of Verrucomicrobia dramatically increased in the Ob-Pre mice (Fig. 2C). Although the absolute abundance was still low, this increase was, on average, >80-fold higher than in the control mice (Table 2). Importantly, the specific species responsible for the increased abundance of Verrucomicrobia was identified as Akkermansia muciniphila (Table 2). In accordance with the pyrosequencing analysis, the different hierarchical clustering analyses and PCoA showed separate clusters corresponding to the dietary treatment (data not shown). In addition to specific changes observed in the pyrosequencing analyses, we found several previously unidentified modifications at level 2 (Table 2).

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