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



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.



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.
Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW., Calgary, Alberta T2N 4N1 Canada.
Christopher
C
Newell
Faculty of Kinesiology, University of Calgary, Calgary, Alberta Canada.
Marc R
MR
Bomhof
Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW., Calgary, Alberta T2N 4N1 Canada ; Faculty of Kinesiology, University of Calgary, Calgary, Alberta Canada.
Raylene A
RA
Reimer
Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW., Calgary, Alberta T2N 4N1 Canada.
Dustin S
DS
Hittel
Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta Canada ; Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta Canada ; Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta Canada.
Jong M
JM
Rho
Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW., Calgary, Alberta T2N 4N1 Canada ; Faculty of Kinesiology, University of Calgary, Calgary, Alberta Canada.
Jane
J
Shearer
D000818:Animals; D000067877:Autism Spectrum Disorder / Q000382:microbiology*; D001419:Bacteria / Q000302:isolation & purification; D001522:Behavior, Animal; D002432:Cecum / Q000382:microbiology; D055423:Diet, Ketogenic; D004195:Disease Models, Animal; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012919:Social Behavior
Autism spectrum disorder; BTBR mouse; Gut microbiome; Ketogenic diet