Differences in the Concentration of the Fecal Neurotransmitters GABA and Glutamate Are Associated with Microbial Composition among Healthy Human Subjects

Abstract

Recent studies have shown that the gut microbiota modulates the physical and psychological functions of the host through several modes of action. One of them is mediating the production of active neurotransmitters, such as serotonin and gamma-aminobutyric acid (GABA). GABA is the major inhibitory neurotransmitter in the central nervous system. Here, we analyzed the relationship between fecal GABA concentration and microbial composition in more than 70 human participants. The gut microbiome composition was analyzed using next-generation sequencing based on 16S ribosomal RNA. High-performance liquid chromatography was used to evaluate the neurotransmitters GABA and glutamate. The GABA level was detected in a broad range (0–330 µg/g feces). The participants’ samples were classified into high (>100 µg/g), medium (10–100 µg/g), and low (<10 µg/g) groups, based on fecal GABA concentration. The results reveal that the microbiome of the high-GABA samples had lower alpha diversity than the other samples. Beta diversity analysis showed significant (p < 0.05) separation between the high-GABA samples and others. Furthermore, we surveyed the abundance of specific GABA producer biomarkers among the microbiomes of tested samples. The family Bifidobacteriaceae exhibited high abundance in the microbiome of the high-GABA group. This study demonstrated that Bifidobacterium abundance was associated with high fecal GABA content in healthy human subjects. These results may aid the development of potential probiotics to improve microbial GABA production, which can support the maintenance of the physical and psychiatric health of the host.

Roles and Mechanisms of Gut Microbiota in Patients With Alzheimer’s Disease

“…GABA, the major inhibitory transmitter in the adult mammalian brain, has been reported in several species belonging to the families Bifidobacteriaceae, Lactobacillaceae, Bacteroidaceae, Enterococcaceae, Propionibacteriaceae, and Streptococcaceae (Duranti et al, 2020;Altaib et al, 2021). Bifidobacterium abundance such as B. adolescentis is associated with high fecal GABA content in healthy human subjects (Duranti et al, 2020;Altaib et al, 2021). Studies in the postmortem brains of patients with AD and animal models have shown substantially reduced levels of GABA in the subregions of the temporal cortex.…”

Dose-Dependent Relationship between Protection of Thioacetamide-Induced Acute Liver Injury and Hyperammonemia and Concentration of Lactobacillus salivarius Li01 in Mice

“…From the fecal 16S rRNA gene sequencing results, group B was rich in bifidobacterial evolutionary branches. Bifidobacterium has been applied as a probiotic for a long time, and a new study demonstrated that many species of Bifidobacterium exhibited the ability to improve microbial GABA production, which is known to help in maintaining the physical and psychiatric health of the host ( 45 ). The benefit to psychiatric health is particularly important in hyperammonemia, which often leads to psychiatric symptoms.…”

Gut Microbiota Metabolites in Major Depressive Disorder—Deep Insights into Their Pathophysiological Role and Potential Translational Applications

“…Lactobacillus and Bifidobacterium are two central genera involved in the production of glutamate and GABA. Altaib et al [136] found an interesting association between the fecal abundance of the Bifidobacteriaceae family and GABA levels in healthy individuals. Bifidobacterium dentium appears to be a pivotal microorganism involved in GABA production from glutamate, glutamine, and succinate, which was also related to an augmented tyrosine production [137].…”