Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Nov;60(11):2775-86.
doi: 10.2337/db11-0227. Epub 2011 Sep 20.

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

Amandine Everard  1 , Vladimir Lazarevic, Muriel Derrien, Myriam Girard, Giulio G Muccioli, Audrey M Neyrinck, Sam Possemiers, Ann Van Holle, Patrice François, Willem M de Vos, Nathalie M Delzenne, Jacques Schrenzel, Patrice D Cani
Affiliations

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

Amandine Everard et al. Diabetes. 2011 Nov.

Erratum in

  • Diabetes. 2011 Dec;60(12):3307. Muccioli, Giulio M [corrected to Muccioli, Giulio G]

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.

PubMed Disclaimer

Figures

FIG. 1.
FIG. 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.
FIG. 2.
FIG. 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.
FIG. 3.
FIG. 3.
Changes in the gut microbiota improve glucose tolerance and reduce plasma triglyceride content, tissue weight, oxidative stress, and muscle lipid accumulation. A: Plasma glucose profile following 1 g/kg glucose oral challenge in freely moving mice. Inset shows the mean area under the curve (AUC) measured between 0 and 120 min after glucose load in the Ob-CT (■) and the Ob-Pre (○) mice. Mean ± SEM. n = 10 mice/group. *P < 0.05, determined by a two-tailed Student t test. B: White adipose tissue weight expressed as the percentage of total body weight of the Ob-CT and Ob-Pre mice. Mean ± SEM. n = 8 mice/group. *P < 0.05, determined by a two-tailed Student t test. C: Muscle weight (Vastus lateralis) expressed as the percentage of total body weight. D: Plasma triglyceride content. E: Muscle lipid content. F: Muscle triglycerides. G: Muscle lipoprotein lipase (LPL) mRNA expression. H: Adipose tissue lipid peroxidation markers (TBARS). I: Plasma LPS levels in the same set of mice. Mean ± SEM. n = 10 mice/group. *P < 0.05, determined by a two-tailed Student t test.
FIG. 4.
FIG. 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.)
FIG. 5.
FIG. 5.
Prebiotic-induced changes in gut microbiota are associated with improved leptin sensitivity and glucose homeostasis in diet-induced obese and diabetic mice. A: Plasma glucose profile after 2 g/kg glucose oral challenge in freely moving mice in the HF (■) and the HF-Pre (□) mice. B: Body weight gain. C: Lean body mass measured by nuclear magnetic resonance. D: Adiposity index, corresponding to the sum of the subcutaneous, the visceral, and the epididymal adipose depot weights. E: Colon proglucagon mRNA expression. F: Portal plasma GLP-1 level content. Mean ± SEM. n = 8 (HF) and 9 (HF-Pre). *P < 0.05; #P = 0.08, determined by a two-tailed Student t test. G: Body weight changes 2 days after twice-daily intraperitoneal leptin (0.375 mg/kg) in the HF (HF-L) and the HF-Pre mice (HF-Pre-L). Data from each group were normalized to their own paired saline control. Mean ± SEM. n = 10 mice/group. *P < 0.05, determined by a two-tailed Student t test. H: Food intake 24 h after two doses of intraperitoneal leptin (Lep) (0.375 mg/kg). Data from each group are compared with their own paired saline control (Sal) vs. leptin. Mean ± SEM. n = 10 mice/group. *P < 0.05, determined by a paired Student t test. I: Adipose tissue acetyl-CoA carboxylase (ACC) mRNA expression 6 h after intraperitoneal leptin (1 mg/kg) or saline in the HF (HF-L) and the HF-Pre mice (HF-Pre-L). Data from each group were normalized to their own saline control. Mean ± SEM. Saline, n = 4 mice/group; leptin, n = 6 mice/group. *P < 0.05, determined by a two-tailed Student t test.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 2010;72:219–246 - PubMed
    1. Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 2005;102:11070–11075 - PMC - PubMed
    1. Bäckhed F, Ding H, Wang T, et al. . The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA 2004;101:15718–15723 - PMC - PubMed
    1. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature 2006;444:1022–1023 - PubMed
    1. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006;444:1027–1031 - PubMed

Publication types

MeSH terms