|VAN DE WOUW, MARCEL - University College Cork|
|VIGANO, GIULIA - University Of Milan|
|Lyte, Joshua - Josh|
|BOEHME, MARCUS - University College Cork|
|GUAL, ANDREU - University Rovira I Virgili|
|WALSH, AARON - University College Cork|
|CRISPIE, FIONA - University College Cork|
|CLARKE, GERARD - University College Cork|
|DINAN, TIMOTHY - University College Cork|
|COTTER, PAUL - University College Cork|
|CRYAN, JOHN - University College Cork|
Submitted to: Brain Behavior and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/3/2021
Publication Date: 10/1/2021
Citation: Van De Wouw, M., Vigano, G.M., Lyte, J.M., Boehme, M., Gual, A., Walsh, A.M., Crispie, F., Clarke, G., Dinan, T.G., Cotter, P.D., Cryan, J.F. 2021. Kefir ameliorates specific microbiota-gut-brain axis impairments in a mouse model relevant to autism spectrum disordor. Brain Behavior and Immunity. 97:119-134. https://doi.org/10.1016/j.bbi.2021.07.004.
Interpretive Summary: The gut microbiome, which is the collection of bacteria that are found in the gut of people or animals, have been shown to affect the behavior and central nervous system (such as some aspects of brain development) of people and animals. Autism spectrum disorder (ASD) is not a single disorder with any single cause, but instead is a wide variety of neurodevelopmental conditions that may include aspects of reduced social communication and repetitive behaviors. Interestingly, the gut microbiome has been suggested to possibly affect ASD, and therefore the microbiome may serve as a therapeutic target in the distant future by which to potentially help treat ASD. Although very little is known how the microbiome, or if the microbiome can help in ASD, basic research must be first carried out to assess any potential role. As the microbiome inhabits the gut, it can be exposed to what people and animals eat in their diets. Kefir is a fermented milk drink that has been shown to affect the microbiome which is associated with, but not directly causative of, affecting some aspects of behavior in animals. Therefore, we sought to understand how kefir consumption could affect an animal model of ASD, and if this may work through the microbiome. Our findings lend important insight into how diet may impact the microbiome to influence a model of ASD.
Technical Abstract: Autism spectrum disorders (ASD) is one of the most severe developmental disorders, affecting on average 1 in 150 children worldwide. There are limited treatment options for ASD symptoms and there is therefore a great need for more effective strategies to improve quality of life in ASD subjects. The gut microbiome has recently emerged as a therapeutic target in ASD. A novel modulator of the gut microbiome, the traditionally fermented milk drink kefir, has recently been shown to modulate the microbiota and decrease repetitive behaviour, one of the hallmarks of ASD. As such, we hypothesised that kefir could ameliorate the behavioural phenotype of ASD in the animal model of ASD; the BTBR T+ Itpr3tf/J mouse strain. Adult mice were administered either kefir (UK4) or milk control for 3 weeks as treatment lead-in, after which they were assessed for their behavioural phenotype using a battery of tests. In addition, we assessed systemic immunity by flow cytometry. We found that kefir decreased repetitive behaviour. Furthermore, kefir prolonged stress-induced increases in corticosterone 60 minutes post-stress, which was accompanied by an ameliorated innate immune response as measured by LY6Chi monocyte levels. Furthermore, kefir increased the levels of anti-inflammatory Treg cells in mesenteric lymph nodes. Altogether, our data show that kefir modulates peripheral immunity in an anti-inflammatory manner and can ameliorate specific ASD behavioural dysfunctions, indicating that kefir supplementation might prove a viable strategy in improving quality of life in ASD subjects.