Potential Roles for Gamma-Aminobutyric Acid Signaling in Bacterial Communities

Abstract

It is now established that the gut microbiome influences human neurology and behavior, and vice versa. Distinct mechanisms underlying this bidirectional communication pathway, termed the gut-brain axis, are becoming increasingly uncovered. This review summarizes recent interkingdom signaling research focused on gammaaminobutyric acid (GABA), a human neurotransmitter and ubiquitous signaling molecule found in bacteria, fungi, plants, invertebrates, and mammals. We detail how GABAergic signaling has been shown to be a crucial component of the gut-brain axis. We further describe how GABA is also being found to mediate interkingdom signaling between algae and invertebrates, plants and invertebrates, and plants and bacteria. Based on these emerging results, we argue that obtaining a complete understanding of GABA-mediated communication in the gut-brain axis will involve deciphering the role of GABA signaling and metabolism within bacterial communities themselves.

Recent advances of γ-aminobutyric acid: Physiological and immunity function, enrichment, and metabolic pathway

“…The delicate balance between GABAergic inhibitory neurons and Glu excitable neurons in the brain is the key to the correct functioning of brain. The destruction of this balance is not only related to schizophrenia, autism, epilepsy, and other neuropsychiatric diseases ( 7 ) but also related to acquired immune diseases ( 8 , 9 ). A newly published paper showed that GABAergic regulated the intestinal innate immune response which help to maintain immune homeostasis ( 10 ).…”

The correlation between gut microbiota and both neurotransmitters and mental disorders: A narrative review

“…[35] GABA can also be produced from ornithine, arginine, and putrescine, and numerous human gut bacteria have been found to contain homologous biosynthesis enzymes. [36] Bacteria use neurotransmitters to communicate with the CNS and release molecules into the bloodstream that regulate physiological processes in the intestinal wall. [37] The Parabacteroides and Eubacterium genera were identified as GABA producers, [38] along with Lactobacillus, Bifidobacterium, Bacteroides, [37] and Blautia, [39] specifically Bacteroides fragilis.…”

Deteriorating microbiomes in agriculture - the unintended effects of pesticides on microbial life

“…Dichlorodiphenyltrichloroethane (DDT) is another well-known OCL with potent antibacterial properties, and under field conditions causes a ~60% decrease in active soil bacterial biomass and a ~93% increase in fungal biomass [28] -the latter of which likely represents an indirect response to the former via reduced competition, rather than a stimulatory response to DDT since OCLs are notoriously recalcitrant to breakdown. Importantly, the mechanism by which OCLs exert their differential antimicrobial effects has long been assumed to be through non-specific physicochemical disruption of (primarily Gram-positive) membraneassociated processes (e.g., ionic transport, electron transport, cell wall biosynthesis), ultimately leading to cell lysis and loss of viability [48] . That is, the antimicrobial effects of OCLs were thought to be random and independent from their designed functions of inhibiting insect GABAergic signalling.…”

“…Taken together, this suggests that the antimicrobial effects of OCLs are not random and may in fact be related to their inhibitory effects on GABAergic signalling. While OCLs are now banned in most countries due to their environmental persistence (facilitated at least in part by inhibition of their own bioremediation [48] ) and association with a broad range of other wildlife health concerns [51] , they provide an exemplary account of host-microbiome interconnectedness and how intentional insecticidal properties can directly translate into unintentional microbicidal properties [Figure 1].…”