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

Abstract

BackgroundGastrointestinal 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 BTBRT + 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.FindingsJuvenile 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.ConclusionsResults 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13229-016-0099-3) contains supplementary material, which is available to authorized users.

Sex-related alterations of gut microbiota composition in the BTBR mouse model of autism spectrum disorder

“…Genus Sutterella, within Proteobacteria, was found to be elevated both in feces of ASD children and in intestinal biopsies from children with autism and intestinal disturbances3536. Furthermore, high levels of Akkermansia muciniphila were reported in BTBR fed a chow diet, while the ketogenic diet resulted in a normalization of its levels in association with improvement of behavioral symptoms37. Genus Oscillospira accounted for 13.7% in fC57 and was found significantly reduced to 5.4% in fBTBR.…”

A modified ketogenic gluten-free diet with MCT improves behavior in children with autism spectrum disorder

“…The gut microbiome may serve as another worthwhile area of investigation in light of recent studies showing the importance of commensal bacteria in the gut in association with healthy brain function [47]. Animal studies of ASD have supported links between the KD and gut microbiome and mitochondrial changes [48,49]. Future research will need to identify the key bacteria and cellular mechanisms that are modified by the KD and that are associated with improvements in ASD behavior in humans.…”

The BTBR mouse model of idiopathic autism – Current view on mechanisms

“…Several explanations have been proposed, including a shift from glucose to ketone bodies metabolism in the brain, anticonvulsive properties of certain components of the diet, and a change in electrolyte balance (acidosis). A recent report by Newell and collaborators (2016) suggests that ketogenic diet may also reduce otherwise elevated numbers of certain gut microbiota, characteristic of ASD phenotype. Whether any of these are actually responsible for the alleviation of ASD-like symptoms in BTBR mice is not known at this point.…”