Distinct actions of the fermented beverage kefir on host behaviour, immunity and microbiome gut-brain modules in the mouse

Abstract

Background: 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. Methods: To address this, two distinct kefirs (Fr1 and UK4), or unfermented milk control, were administered to mice that underwent a battery of tests to characterise their behavioural phenotype. In addition, shotgun metagenomic sequencing of ileal, caecal and faecal matter was performed, as was faecal metabolome analysis. Finally, systemic immunity measures and gut serotonin levels were assessed. Statistical analyses were performed by ANOVA followed by Dunnett's post hoc test or Kruskal-Wallis test followed by Mann-Whitney U test. Results: 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. Furthermore, UK4 increased fear-dependent contextual memory, yet decreased milk gavage-induced improvements in long-term spatial learning. 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 Lactobacillus reuteri.

Kefir and Intestinal Microbiota Modulation: Implications in Human Health

“…The ability to modulate the intestinal microbiota and, consequently, anxiety and depression also suggests a positive role of kefir in these diseases ( 38 , 42 ) ( Table 1 ). Animals fed with kefir presented a specific intestinal microbiota composition, which presumably acts positively on the gut-brain axis.…”

“…In addition, through analysis of the microbiome, authors suggest that kefir was able to stimulate the production of the gamma aminobutyric acid (GABA). It is hypothesized that Lactobacillus reuteri possibly converted 2-oxoglutarate to glutamate, which was subsequently converted into GABA, because of modulation of the intestinal microbiota by kefir, that leads to an increase in the production of Lactobacillus reuteri , a bacterial strain with benefits to the host's immune and metabolic system ( 42 ).…”

Microbial community dynamics of fermented kefir beverages changes over time

“…2019; van de Wouw et al . 2020). The current scenario has resulted in growing interest in probiotics using, since they are known for providing different health benefits, such as gut homeostasis maintenance, intestinal dysbiosis prevention or reversal (Zhong et al .…”

Psychobiotics: Mechanisms of Action, Evaluation Methods and Effectiveness in Applications with Food Products

“…They also changed the composition of the host microbiota and differentially impacted systemic immunity and colonic serotonergic signaling. Besides, kefir consumption influenced specific gut microbial functional capacities, including GABA’s biosynthesis linked to an increased prevalence of Lactobacillus reuteri [ 89 ].…”