Priority CommunicationObese-type Gut Microbiota Induce Neurobehavioral Changes in the Absence of Obesity
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Animals and Treatments
The Pennington Biomedical Research Center Institutional Animal Care and Use Committee approved all experimental protocols, which were compliant with National Institutes of Health guidelines. To generate microbiota donor material, 8-week-old male C57BL/6 mice (Jackson Laboratories, Bar Harbor, Maine) were given regular chow diet (13% fat calories, Purina LabDiet 5001; LabDiet, St. Louis, Missouri) or high-fat diet (60% fat calories, Research Diets D12492; Research Diets, Inc., New Brunswick, New
HFD-Derived Gut Microbiota Impair Behavioral Performance in Mice
All animals tolerated the antibiotic regimen with no overt effects other than a mild, approximate 10% loss of body weight (Figure 1A). Quantitative real-time polymerase chain reaction based analyses of 16S RNA levels in fecal samples collected from mice midway through the antibiotic treatment revealed an approximate 90% to 95% reduction in fecal bacteria burden compared with matched but untreated mice (fecal DNA concentration 82,502.1 ± 18,255 µg/g in control samples, 3417.4 ± 1212 µg/g in
Discussion
The present findings represent the first definitive evidence that high-fat diet-induced changes to the gut microbiome are sufficient to disrupt brain physiology and function in the absence of obesity. Specifically, data show that transplantation of microbiota shaped by high-fat diet, but not control low-fat diet, caused significant and selective disruptions in exploratory, cognitive, and stereotypical behavior in conventionally housed, nonobese, diet-naïve mice. Overall, these data are in
Acknowledgments and Disclosures
This work was supported by the National Institutes of Health (DK047348 to HRB) and also used Pennington Biomedical Research Center (Animal Phenotyping) and Louisiana State University (Microbial Genomics Resource Center), which are funded, in part, by the National Institutes of Health (P20-RR021945, P30-DK072476, and P60-AA009803).
We thank Dr. Barry Robert for expert veterinary assistance related to antibiotic administration.
The authors declare no biomedical financial interests or potential
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