Cited by 272Gut microbiota and healthAutism Spectrum Disorder ResearchDiet and metabolism studies

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Ketogenic diet modifies the gut microbiota in a murine model of autism spectrum disorder

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Newell, Christopher, Bomhof, Marc R., Reimer, Raylene A., Hittel, Dustin S., Rho, Jong M., Shearer, Jane·2016·Molecular Autism

DOI 10.1186/s13229-016-0099-3PMC PMC5009541

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Abstract

BACKGROUND: Gastrointestinal dysfunction and gut microbial composition disturbances have been widely reported in autism spectrum disorder (ASD). This study examines whether gut microbiome disturbances are present in the BTBR(T + tf/j) (BTBR) mouse model of ASD and if the ketogenic diet, a diet previously shown to elicit therapeutic benefit in this mouse model, is capable of altering the profile. FINDINGS: Juvenile male C57BL/6 (B6) and BTBR mice were fed a standard chow (CH, 13 % kcal fat) or ketogenic diet (KD, 75 % kcal fat) for 10-14 days. Following diets, fecal and cecal samples were collected for analysis. Main findings are as follows: (1) gut microbiota compositions of cecal and fecal samples were altered in BTBR compared to control mice, indicating that this model may be of utility in understanding gut-brain interactions in ASD; (2) KD consumption caused an anti-microbial-like effect by significantly decreasing total host bacterial abundance in cecal and fecal matter; (3) specific to BTBR animals, the KD counteracted the common ASD phenotype of a low Firmicutes to Bacteroidetes ratio in both sample types; and (4) the KD reversed elevated Akkermansia muciniphila content in the cecal and fecal matter of BTBR animals. CONCLUSIONS: Results indicate that consumption of a KD likely triggers reductions in total gut microbial counts and compositional remodeling in the BTBR mouse. These findings may explain, in part, the ability of a KD to mitigate some of the neurological symptoms associated with ASD in an animal model.

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Fig. 1 Assessment of total microbial content, partial least squares discriminant analysis (PLS-DA), and variable importance of projection (VIP) scores for relative bacterial abundance. Descriptive comparisons of total microbial content, score plots of PLS-DA, and VIP scores for both cecal and fecal matter are presented. a Total bacterial species composition measured from cecal matter. b Total bacterial species composition measured from fecal matter. c PLS-DA score plot for cecal matter showing model discrimination between each genotype. d PLS-DA score plot for fecal matter showing model discrimination between each genotype. e Cecal VIP plot indicating the most discriminating bacteria in descending order of importance. f Fecal VIP plot indicating the most discriminating bacteria in descending order of importance. Statistical comparisons between genotype and diet were determined by ANOVA, followed by Tukey’s post hoc test. PLS-DA and VIP scores were assessed using MetaboAnalyst 3.0. Ellipses represent 95 % confidence intervals for each individual group on PLS-DA plots with Q 2 and R 2 values being used to assess the robustness of the model and the amount of variation represented by the principal components, respectively. VIP scores reflect the degree of importance of a bacteria, with values >1.0 seen as driving the calculated discrimination. All data were collected using qRT-PCR and are presented as mean 16S rRNA gene copies/mg of corresponding tissue ± SEM (CC, B6-chow; CK, B6-ketogenic; BC, BTBR-chow; and BK, BTBR-ketogenic; n = 11, 10, 15, and 10, respectively). p < 0.01 if values do not share a superscript letter. An adapted version of this table has been previously published. Reprinted with permission of the American Chemical Society, Copyright 2016CC BY · PubMed Central

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Authors: Newell, C., Bomhof, M. R., Reimer, R. A., Hittel, D. S., Rho, J. M., & Shearer, J.
Affiliations: University of Calgary (CA)
Corresponding author: Newell, Christopher
ORCID: Bomhof, Marc R.
Reimer, Raylene A.
Rho, Jong M.
Shearer, Jane
Venue: Molecular Autism
Publisher: Springer Science and Business Media LLC
Published: 2016-09-01
Volume: 7
Issue: 1
Pages: 37-37
ISSN: 2040-2392 (ISSN-L)
DOI: 10.1186/s13229-016-0099-3
PMC: PMC5009541
OpenAlex: W2509638174
Cited by: 272
References: 30
Citations by year: 2026: 13 · 2025: 30 · 2024: 23 · 2023: 31 · 2022: 41 · 2021: 33 · 2020: 40 · 2019: 29 · 2018: 20 · 2017: 10 · 2016: 2
FWCI: 10.56
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Molecular Autism (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion)
eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders: Alberta Children's Hospital Foundation
Canadian Institutes of Health Research
MitoCanada
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Health Sciences › Medicine › Physiology (medical) › Diet and metabolism studies
Keywords: ketogenic diet, autism spectrum disorder, gut microbiota, gut-brain axis, Akkermansia muciniphila, Firmicutes/Bacteroidetes ratio, cecal microbiota, fecal microbiota, dietary fat, gastrointestinal dysfunction
MeSH terms: Autism Spectrum Disorder, Gastrointestinal Microbiome, Animals, Bacteria, Behavior, Animal, Cecum, Disease Models, Animal, Feces, Male, Mice, Inbred C57BL, Social Behavior, Mice, Diet, Ketogenic

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Ketogenic diet modifies the gut microbiota in a murine model of autism spectrum disorder

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