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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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Prebiotic-induced changes in gut microbiota are associated with increased enteroendocrine L-cell number in obese mice. A: Portal plasma GLP-1 levels. B: Proglucagon mRNA expression measured in the colon. Mean ± SEM. n = 10 mice/group. *P < 0.05, determined by a two-tailed Student t test. C: L-cell number expressed per mm2 of colon. D: Representative immunofluorescence staining of L cells using a GLP-1 antibody. Mean ± SEM. n = 4–6 mice/group. *P < 0.05, determined by a two-tailed Student t test. (A high-quality digital representation of this figure is available in the online issue.)
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Figure 4: Prebiotic-induced changes in gut microbiota are associated with increased enteroendocrine L-cell number in obese mice. A: Portal plasma GLP-1 levels. B: Proglucagon mRNA expression measured in the colon. Mean ± SEM. n = 10 mice/group. *P < 0.05, determined by a two-tailed Student t test. C: L-cell number expressed per mm2 of colon. D: Representative immunofluorescence staining of L cells using a GLP-1 antibody. Mean ± SEM. n = 4–6 mice/group. *P < 0.05, determined by a two-tailed Student t test. (A high-quality digital representation of this figure is available in the online issue.)

Mentions: Several lines of evidence suggest that prebiotic treatment promotes the production of GLP-1 and GLP-2 by enteroendocrine L cells (8,16,20,34,35). However, the exact contribution of the gut microbiota modulation associated with prebiotic treatment to L-cell number in obese mice is unclear. Strikingly, the prebiotic-treated mice exhibited a twofold increase in the L-cell number in the colon (Fig. 4C) and a similar increase in the proglucagon mRNA level (Fig. 4B). L-cell number and proglucagon mRNA level similarly increased in the jejunum after the prebiotic-induced gut microbiota modulation (Supplementary Fig. 5A–C). In accordance with these findings, we found that prebiotic feeding increases portal plasma GLP-1 levels (Fig. 4A), whereas GIP tends to decrease in Ob-pre mice (Ob-CT 280.4 ± 42.9, Ob-Pre 204.7 ± 15.8; P = 0.1). Given that the prebiotic treatment significantly increased colon weight and length (Table 3), it is likely that this effect is attributed to a greater pool of L cells within the intestine.


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)

Prebiotic-induced changes in gut microbiota are associated with increased enteroendocrine L-cell number in obese mice. A: Portal plasma GLP-1 levels. B: Proglucagon mRNA expression measured in the colon. Mean ± SEM. n = 10 mice/group. *P < 0.05, determined by a two-tailed Student t test. C: L-cell number expressed per mm2 of colon. D: Representative immunofluorescence staining of L cells using a GLP-1 antibody. Mean ± SEM. n = 4–6 mice/group. *P < 0.05, determined by a two-tailed Student t test. (A high-quality digital representation of this figure is available in the online issue.)
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 4: Prebiotic-induced changes in gut microbiota are associated with increased enteroendocrine L-cell number in obese mice. A: Portal plasma GLP-1 levels. B: Proglucagon mRNA expression measured in the colon. Mean ± SEM. n = 10 mice/group. *P < 0.05, determined by a two-tailed Student t test. C: L-cell number expressed per mm2 of colon. D: Representative immunofluorescence staining of L cells using a GLP-1 antibody. Mean ± SEM. n = 4–6 mice/group. *P < 0.05, determined by a two-tailed Student t test. (A high-quality digital representation of this figure is available in the online issue.)
Mentions: Several lines of evidence suggest that prebiotic treatment promotes the production of GLP-1 and GLP-2 by enteroendocrine L cells (8,16,20,34,35). However, the exact contribution of the gut microbiota modulation associated with prebiotic treatment to L-cell number in obese mice is unclear. Strikingly, the prebiotic-treated mice exhibited a twofold increase in the L-cell number in the colon (Fig. 4C) and a similar increase in the proglucagon mRNA level (Fig. 4B). L-cell number and proglucagon mRNA level similarly increased in the jejunum after the prebiotic-induced gut microbiota modulation (Supplementary Fig. 5A–C). In accordance with these findings, we found that prebiotic feeding increases portal plasma GLP-1 levels (Fig. 4A), whereas GIP tends to decrease in Ob-pre mice (Ob-CT 280.4 ± 42.9, Ob-Pre 204.7 ± 15.8; P = 0.1). Given that the prebiotic treatment significantly increased colon weight and length (Table 3), it is likely that this effect is attributed to a greater pool of L cells within the intestine.

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