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01.12.2014 | Research article | Ausgabe 1/2014 Open Access

Molecular Neurodegeneration 1/2014

Diet and exercise orthogonally alter the gut microbiome and reveal independent associations with anxiety and cognition

Molecular Neurodegeneration > Ausgabe 1/2014
Silvia S Kang, Patricio R Jeraldo, Aishe Kurti, Margret E Berg Miller, Marc D Cook, Keith Whitlock, Nigel Goldenfeld, Jeffrey A Woods, Bryan A White, Nicholas Chia, John D Fryer
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1750-1326-9-36) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

SSK, NC, and JDF designed and performed this study, analyzed data, and wrote the manuscript. PRJ, MEBM, MDC, KW, NG, JAW, and BAW assisted in purification, sequencing, and analysis of fecal DNA. AK assisted in behavioral analysis. All authors discussed the results and provided comments on the manuscript. All authors read and approved the final manuscript.



The ingestion of a high-fat diet (HFD) and the resulting obese state can exert a multitude of stressors on the individual including anxiety and cognitive dysfunction. Though many studies have shown that exercise can alleviate the negative consequences of a HFD using metabolic readouts such as insulin and glucose, a paucity of well-controlled rodent studies have been published on HFD and exercise interactions with regard to behavioral outcomes. This is a critical issue since some individuals assume that HFD-induced behavioral problems such as anxiety and cognitive dysfunction can simply be exercised away. To investigate this, we analyzed mice fed a normal diet (ND), ND with exercise, HFD diet, or HFD with exercise.


We found that mice on a HFD had robust anxiety phenotypes but this was not rescued by exercise. Conversely, exercise increased cognitive abilities but this was not impacted by the HFD. Given the importance of the gut microbiome in shaping the host state, we used 16S rRNA hypervariable tag sequencing to profile our cohorts and found that HFD massively reshaped the gut microbial community in agreement with numerous published studies. However, exercise alone also caused massive shifts in the gut microbiome at nearly the same magnitude as diet but these changes were surprisingly orthogonal. Additionally, specific bacterial abundances were directly proportional to measures of anxiety or cognition.


Thus, behavioral domains and the gut microbiome are both impacted by diet and exercise but in unrelated ways. These data have important implications for obesity research aimed at modifications of the gut microbiome and suggest that specific gut microbes could be used as a biomarker for anxiety or cognition or perhaps even targeted for therapy.
Additional file 1: Figure S1: Impact of diet and exercise on other mouse behaviors. Neither HFD nor exercise altered total locomotor activity (A) or rearing (B) in the open field assay or in sociability (C) in the three chamber social test. As with the contextual memory, exercised mice had a trend toward increased cued memory (D, p = 0.051) in the cued portion of the contextual fear conditioning assay. (PDF 122 KB)
Additional file 2: Table S2: OTU and probabilities of correct taxonomic classification (in parentheses). (PDF 157 KB)
Additional file 3: Table S1: Significant effects of diet and exercise at different levels of taxonomy. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. (PDF 33 KB)
Additional file 4: Figure S2: Anxiety levels were associated with several bacteria at the level of phyla, class, order, and family. Color scheme of data points follows the format as in Figure 1 (ND = blue, ND + exercise = green, HFD = red, and HFD + exercise in orange). Linear regression analysis for individual mice was performed with R2 values indicating goodness of fit and uncorrected p values for slope calculated by F test. (PDF 232 KB)
Additional file 5: Table S3: Associations of bacterial abundances with body weight. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. (PDF 27 KB)
Authors’ original file for figure 1
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