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

Mol Autism. 2016 Sep 1;7(1):37. doi: 10.1186/s13229-016-0099-3. eCollection 2016.

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.

Keywords: Autism spectrum disorder; BTBR mouse; Gut microbiome; Ketogenic diet.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autism Spectrum Disorder / microbiology*
  • Bacteria / isolation & purification
  • Behavior, Animal
  • Cecum / microbiology
  • Diet, Ketogenic*
  • Disease Models, Animal
  • Feces / microbiology
  • Gastrointestinal Microbiome*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Social Behavior

Grant support