|VAN DE WOUW, MARCEL - University College Cork|
|WALSH, AARON - University College Cork|
|CRISPIE, FIONA - University College Cork|
|VAN LEUVEN, LUCAS - University College Cork|
|Lyte, Joshua - Josh|
|BOEHME, MARCUS - 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: Microbiome
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/26/2020
Publication Date: 5/18/2020
Citation: Van De Wouw, M., Walsh, A.M., Crispie, F., Van Leuven, L., Lyte, J.M., Boehme, M., Clarke, G., Dinan, T.G., Cotter, P.D., Cryan, J.F. 2020. Distinct actions of the fermented beverage kefir on host behaviour, immunity and microbiome gut-brain modules in the mouse. Microbiome. https://doi.org/10.1186/s40168-020-00846-5.
Interpretive Summary: Kefir is a fermented milk drink that is consumed across the world. The gut microbiota, which consists of bacteria and other organisms in the gut, can affect the host, which is the person or animal. When a person drinks kefir, this is associated with changes in composition, such as species, of bacteria in the gut microbiota. In this study, we hypothesized that some of these kefir-associated changes in the gut microbiota may have beneficial impact on host health. Mice were fed one of two types of kefir or a regular milk drink, and evaluated for behaviour. In addition we examined changes in the microbiota as well as gut serotonin following kefir consumption. We observed that kefir-fed mice had distinct behavioural changes, as well as changes in the microbiota, and gut serotonin. Together, these changes show that kefir can alter the gut microbiota to potentially positively influence host behaviour. The implications of these findings suggest kefir may be a route by which diet can affect the gut microbiota to associate with positive influence on the host.
Technical Abstract: Mounting evidence suggests a role for the gut microbiota in modulating brain physiology and behaviour through bi-directional communication along the gut-brain axis. As such, the gut microbiota represents a potential therapeutic target for influencing centrally-mediated events and host behaviour. It is thus notable that the fermented milk beverage kefir has recently been shown to modulate the composition of the gut microbiota in mice. It is unclear whether kefirs have differential effects on microbiota-gut-brain axis and whether they can modulate host behaviour per se. To address this, two distinct kefirs (Fr1 and UK4) or unfermented milk control were administered to male adult mice that underwent a battery of behavioural tests to characterise their behavioural phenotype. In addition, shotgun metagenomic sequencing of ileal, cecal and faecal matter was performed, as was faecal metabolome analysis. In addition, systemic immunity measures and gut serotonin levels were assessed. Kefir-induced behavioural, immunological and serotonergic alterations that were kefir-specific. Fr1 ameliorated the stress-induced decrease in serotonergic signalling in the colon and reward-seeking behaviour in the saccharin preference test. On the other hand, UK4 decreased repetitive behaviour and ameliorated stress-induced deficits in reward-seeking behaviour in the female urine sniffing test. Furthermore, UK4 impaired long-term spatial learning, yet increased fear-dependent contextual memory. In the peripheral immune system, UK4 increased the prevalence of Treg cells and interleukin 10 levels, whereas Fr1 ameliorated the milk gavage stress-induced elevation in neutrophil levels and CXCL1 levels. Analysis of the gut microbiota revealed that both kefirs significantly changed the composition and functional capacity of the host microbiota, where specific bacterial species were changed in a kefir-dependent manner. Furthermore, both kefirs increased the capacity of the gut microbiota to produce GABA, which was linked to an increased prevalence in L. reuteri. Altogether, these data show that kefir can signal through the microbiota-gut-immune-brain axis and modulate host behaviour. In addition, different kefirs may direct the microbiota toward distinct immunological and behavioural modulatory effects. These results indicate that kefir can positively modulate the microbiota-gut-brain axis and support the broadening of the definition of psychobiotic to include fermented foods such as kefir.