Regulation of gut microbiota and serum neurotransmitters in mice by Streptococcus thermophilus GA8‐ and Lacticaseibacillus rhamnosus HAO9‐fermented milk containing high levels of gamma‐aminobutyric acid

Abstract

AbstractBACKGROUNDGamma‐aminobutyric acid (GABA) is an important neurotransmitter in the human body, with several negative emotions reported as being associated with GABA dysregulation. This study investigates the safety and modulatory effects of GABA‐enriched milk, fermented by Streptococcus thermophilus GA8 and Lacticasebacillus rhamnosus HAO9, on the gut microbiota and neurotransmitter profiles in mice.RESULTSThrough rigorous culturing and fermentation processes, we achieved consistent GABA production in milk, with concentrations reaching 4.6 and 8.5 g L−1 for GA8‐fermented and co‐fermented milk, respectively, after 48 h. Using SPF male C57BL/6J mice, we administered either mono‐culture or combined‐culture milk treatments and monitored physiological impacts. The treatments did not affect mouse body weight but induced significant changes in gut microbiota composition. Beta diversity analysis revealed distinct microbial profiles between treatment groups, highlighting fermentation‐specific microbial shifts, such as an increase in Verrucomicrobia for the GA8 group and a modulation in Saccharibacteria_genera_incertae_sedis for the GA8 + HAO9 group. Serum neurotransmitter levels were elevated in both treatment groups, with significant increases in l‐glutamine, l‐tryptophan and, notably, serotonin hydrochloride in the GA8 + HAO9 group. Correlation analysis identified a positive association between specific bacterial genera and neurotransmitter levels, suggesting a probiotic effect on neuroactive substances.CONCLUSIONThese findings suggest that fermented milk has potential as a probiotic supplement for mood improvement and stress relief, highlighting its role in modulating the gut–brain axis. © 2024 Society of Chemical Industry.