Dataset Information

Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity.

ABSTRACT:

Background

The prevalence of mental illness, particularly depression and dementia, is increased by obesity. Here, we test the hypothesis that obesity-associated changes in gut microbiota are intrinsically able to impair neurocognitive behavior in mice.

Methods

Conventionally housed, nonobese, adult male C57BL/6 mice maintained on a normal chow diet were subjected to a microbiome depletion/transplantation paradigm using microbiota isolated from donors on either a high-fat diet (HFD) or control diet. Following re-colonization, mice were subjected to comprehensive behavioral and biochemical analyses.

Results

The mice given HFD microbiota had significant and selective disruptions in exploratory, cognitive, and stereotypical behavior compared with mice with control diet microbiota in the absence of significant differences in body weight. Sequencing-based phylogenetic analysis confirmed the presence of distinct core microbiota between groups, with alterations in α- and β-diversity, modulation in taxonomic distribution, and statistically significant alterations to metabolically active taxa. HFD microbiota also disrupted markers of intestinal barrier function, increased circulating endotoxin, and increased lymphocyte expression of ionized calcium-binding adapter molecule 1, toll-like receptor 2, and toll-like receptor 4. Finally, evaluation of brain homogenates revealed that HFD-shaped microbiota increased neuroinflammation and disrupted cerebrovascular homeostasis.

Conclusions

Collectively, these data reinforce the link between gut dysbiosis and neurologic dysfunction and suggest that dietary and/or pharmacologic manipulation of gut microbiota could attenuate the neurologic complications of obesity.

SUBMITTER: Bruce-Keller AJ

PROVIDER: S-EPMC4297748 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Publications

Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity.

Bruce-Keller Annadora J AJ Salbaum J Michael JM Luo Meng M Blanchard Eugene E Taylor Christopher M CM Welsh David A DA Berthoud Hans-Rudolf HR

Biological psychiatry 20140718 7

<h4>Background</h4>The prevalence of mental illness, particularly depression and dementia, is increased by obesity. Here, we test the hypothesis that obesity-associated changes in gut microbiota are intrinsically able to impair neurocognitive behavior in mice.<h4>Methods</h4>Conventionally housed, nonobese, adult male C57BL/6 mice maintained on a normal chow diet were subjected to a microbiome depletion/transplantation paradigm using microbiota isolated from donors on either a high-fat diet (HFD ...[more]

PMID: 25173628

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Project description:BackgroundObesity induced by a high-caloric diet has previously been associated with changes in the gut microbiota in mice and in humans. In this study, pigs were cloned to minimize genetic and biological variation among the animals with the aim of developing a controlled metabolomic model suitable for a diet-intervention study. Cloning of pigs may be an attractive way to reduce genetic influences when investigating the effect of diet and obesity on different physiological sites. The aim of this study was to assess and compare the changes in the composition of the gut microbiota of cloned vs. non-cloned pigs during development of obesity by a high-fat/high-caloric diet. Furthermore, we investigated the association between diet-induced obesity and the relative abundance of the phyla Firmicutes and Bacteroidetes in the fecal-microbiota. The fecal microbiota from obese cloned (n = 5) and non-cloned control pigs (n= 6) was investigated biweekly over a period of 136 days, by terminal restriction fragment length polymorphism (T-RFLP) and quantitative real time PCR (qPCR).ResultsA positive correlation was observed between body-weight at endpoint and percent body-fat in cloned (r=0.9, P<0.0001) and in non-cloned control pigs (r=0.9, P<0.0001). Shannon Weaver and principal component analysis (PCA) of the terminal restriction fragments (T-RFs) revealed no differences in the bacterial composition or variability of the fecal microbiota between the cloned pigs or between cloned and non-cloned control pigs. Body-weight correlated positively with the relative abundance of Firmicutes in both cloned (r=0.37; P<0.02) and non cloned-control pigs (r=0.45; P<0.006), and negatively with the abundance of Bacteroidetes in cloned pigs (r=-0.33, P<0.04), but not in the non-cloned control pigs.ConclusionThe cloned pigs did not have reduced inter-individual variation as compared to non-cloned pigs in regard to their gut microbiota in neither the obese nor the lean state. Diet-induced obesity was associated with an increase in the relative abundance of Firmicutes over time. Our results suggest that cloned pigs are not a more suitable animal model for gut microbiota-obesity related studies than non-cloned pigs. This study is the first to evaluate if cloned pigs provide a better animal model than conventional pigs in diet-intervention, obesity and gut microbiota research.

Project description:BackgroundObesity is a growing health concern worldwide, including United Arab Emirates. Bariatric surgery is an effective treatment option, with to date unclear weight loss mechanisms. In this prospective study, we explored post-bariatric surgery changes in energy homeostasis, gut peptides, hormones, and gut microbiota.MethodWe recruited 19 Emirati adults who were planning to undergo sleeve gastrectomy (SG). We assessed the energy requirements using 24-hour diet recalls, indirect calorimetry for resting energy expenditure (REE), and a questionnaire for appetite. Anthropometrics included body mass index (BMI), waist circumference, waist-to-height ratio, fat mass, fat-free mass, and percentage of body fat. Gut peptides, including peptide YY (PYY), glucagon-like peptide-1/2 (GLP-1/2), ghrelin (GHR), cholecystokinin (CCK), insulin, and leptin, were quantified using ELISA. Gut microbiota composition at phylum and genus levels, including the Firmicutes/Bacteroidetes (F/B) ratio and alpha (α) and beta (β) diversity, was determined by sequencing amplicons of the V3-V4 region of the 16S rRNA at baseline and three months post-surgery. Comparisons used paired sample T-test, Wilcoxon, and McNemar test. QIIME 2 was used to identify taxa and their relative abundance; subsequent analyses were done in R for (α) and (β) diversity (package qiime2R) and Wilcoxon signed-rank test in R for differences in microbiota at phylum and genus levels. We conducted Spearman correlation analyses between genera and energy homeostasis, appetite, anthropometrics, hormones, and gut peptides.ResultsAt three months post-SG, energy intake, appetite, all anthropometric indices, insulin, leptin, and GLP-1 significantly decreased; PYY and GHR significantly increased, and REE was stable. β-diversity of the gut microbiota and its composition at phylum and genus levels significantly changed post-surgery, yet F/B remained constant. Energy intake, BMI, and appetite negatively correlated with several taxa that significantly increased post-SG.ConclusionGut peptides, hormones, and microbiota change partly account for bariatric surgery's weight-loss benefits. Understanding these alterations can inform personalized interventions targeting obesity.

Dataset Information

Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity.

Background

Methods

Results

Conclusions

Publications

Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity.

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