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
References (63)
- et al.
A review of the evidence from family, twin and adoption studies for a genetic contribution to adult psychiatric disorders
Int Rev Psychiatry
(2004) - et al.
Obesity and vulnerability of the CNS
Biochim Biophys Acta
(2009) - et al.
Lower cognitive function in the presence of obesity and hypertension: The Framingham Heart Study
Int J Obes Relat Metab Disord
(2003) - et al.
Interactive relations of central versus total obesity and blood pressure to cognitive function
Int J Obes (Lond)
(2006) - et al.
Trajectories of change in obesity and symptoms of depression: The CARDIA study
Am J Public Health
(2010) - et al.
Obesity and depression in US women: Results from the 2005-2006 National Health and Nutritional Examination Survey
Obesity (Silver Spring)
(2010) - et al.
Obesity effects on depression: Systematic review of epidemiological studies
Int J Obes (Lond)
(2008) - et al.
The relationship between abdominal fat, obesity, and common mental disorders: Results from the HUNT study
J Psychosom Res
(2009) - et al.
High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway
PLoS One
(2012) - et al.
Linking the gut microbiota to human health
Br J Nutr
(2013)
The adoptive transfer of behavioral phenotype via the intestinal microbiota: Experimental evidence and clinical implications
Curr Opin Microbiol
Regulation of innate and adaptive immunity by the commensal microbiota
Curr Opin Immunol
Gut microbiota and gastrointestinal health: Current concepts and future directions
Neurogastroenterol Motil
The microbiome and cancer
Nat Rev Cancer
Effect of intestinal microbial ecology on the developing brain
JAMA Pediatr
Probiotics in the treatment of depression: Science or science fiction?
Aust N Z J Psychiatry
Linkage of gut microbiome with cognition in hepatic encephalopathy
Am J Physiol Gastrointest Liver Physiol
Intestinal microbiota, probiotics and mental health: From Metchnikoff to modern advances. Part III - convergence toward clinical trials
Gut Pathog
The role of gut microbiota in the gut-brain axis: Current challenges and perspectives
Protein Cell
Normal gut microbiota modulates brain development and behavior
Proc Natl Acad Sci U S A
Depletion of murine intestinal microbiota: Effects on gut mucosa and epithelial gene expression
PLoS One
Can microbiota transplantation abrogate murine colonization resistance against Campylobacter jejuni?
Eur J Microbiol Immunol (Bp)
Intestinal microbiota containing Barnesiella species cures vancomycin-resistant Enterococcus faecium colonization
Infect Immun
Stochastic changes over time and not founder effects drive cage effects in microbial community assembly in a mouse model
ISME J
The use of the elevated plus maze as an assay of anxiety-related behavior in rodents
Nat Protoc
A detailed ethological analysis of the mouse open field test: Effects of diazepam, chlordiazepoxide and an extremely low frequency pulsed magnetic field
Neurosci Biobehav Rev
Marble burying and nestlet shredding as tests of repetitive, compulsive-like behaviors in mice
J Vis Exp
Obesity increases cerebrocortical reactive oxygen species and impairs brain function
Free Radic Biol Med
The use of behavioral test batteries, II: Effect of test interval
Physiol Behav
Behavioral alterations induced by repeated testing in C57BL/6J and 129S2/Sv mice: Implications for phenotyping screens
Genes Brain Behav
Development of a dual-index sequencing strategy and curation pipeline for analyzing amplicon sequence data on the MiSeq Illumina sequencing platform
Appl Environ Microbiol
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