A single administration of ‘microbial’ D-alanine to healthy volunteers augments reaction to negative emotions: A comparison with D-serine

Abstract

Background: Activation of the glutamate N-methyl-D-aspartate receptor with its co-agonist D-serine has been shown to improve subjective mood in healthy volunteers. D-alanine is another potent N-methyl-D-aspartate receptor co-agonist which arises from the natural breakdown of host gut microbes, and is predominantly sequestered in the pituitary. This may suggest that D-alanine influences the neuroendocrine stress response which may then impact on emotion. Aims: The current study explored the effects of D-serine and D-alanine on emotional processing, cognition and the levels of the stress hormone cortisol in healthy volunteers. Methods: In a double-blind, placebo-controlled randomised study, participants ( n=63) received a single oral dose of either D-serine, D-alanine (60 mg/kg) or placebo and then performed the Emotional Test Battery and N-back task (two hours post-administration) and provided saliva samples at fixed intervals. Results: Subjects administered with D-alanine were faster at identifying facial expressions of fear, surprise and anger, and at categorising negative self-referential words. Participants on D-alanine also showed a trend to recall more words than placebo in a memory task. D-serine did not have any meaningful effects in any of the tasks. Neither amino acid had a significant effect on salivary cortisol or working memory. Conclusion: This study is the first to suggest that D-alanine can modulate emotional cognitive processing after a single dose. The lack of findings for D-serine nevertheless contrasts a previous study, emphasising a need for further investigation to clarify discrepancies. A better understanding of the physiological actions of D-amino acids would be beneficial in evaluating their therapeutic potential.

A Systematic Review of Psychobiotic Interventions in Children and Adolescents to Enhance Cognitive Functioning and Emotional Behavior

“…A summary of study [ 55 , 56 , 63 , 65 , 67 , 68 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 ] characteristics is depicted in Table 2 . Among the six studies that employed probiotics, a variety of probiotic species and strains were used: Lactobacilli casei Shirota , Lactobacillus plantarum DR7 , Lactobacillus plantarum PS128 , and Lactobacillus rhamnosus , as well as a combination of Bifidobacterium bifidum W23 , Bifidobacterium lactis W51 , Bifidobacterium lactis W52 , Lactobacillus acidophilus W37 , Lactobacillus brevis W63 , Lactobacillus casei W56 , Lactobacillus salivarius W24 , Lactococcus lactis W19 , and Lactococcus lactis W58 (i.e., the Ecologic Barrier formula).…”

Analysis of differential colostrum metabolism in high and low yielding Guanzhong dairy goats

“…Among them, there were six differentially expressed metabolites with the highest relative content in the colostrum of high-yielding Guanzhong dairy goats, namely D-alanine-D-serine, α-lactose, 2'-(6'-coumaroyl glucoside), D-maltose, pravastatin (reductase inhibitor), and diketogulonic acid are the three most abundant differential metabolites in the colostrum of low yielding Guanzhong dairy goats, namely taurocholic acid, hygromycin A, and L-carnitine. D-maltose is the main component and energy supply substance of cellular structure, and has important functions in regulating cellular activity [19] ; D-alanine is another potent N-methyl-D-aspartate receptor co-agonist produced by the natural breakdown of host gut microbiota, which has the ability to affect neuroendocrine stress responses and subsequently affect human emotions [20] ; Statins have the effects of reducing lipid, antioxidation, and anti-inflammatory [21] ; the pravastatin has the effect of reducing the decrease of cytochrome c and mitochondrial oxygen consumption [22] . Lactose is a disaccharide secreted by the mammary glands of mammals and is the main carbohydrate in milk.…”

Multispecies probiotic administration reduces emotional salience and improves mood in subjects with moderate depression: a randomised, double-blind, placebo-controlled study

“…This is an approach that has been accepted for our other studies with the same design where a change in emotional processing was the primary outcome (e.g. Capitão et al, 2020 ).…”