# Gut Microbiota as an Endocrine Organ: Unveiling Its Role in Human Physiology and Health
## 3 Neurohormones and Their Role in Microbial Effects
### Neurohormones: Bridging the Gap between the Brain and Microbial Effects
#### 3.2.2 Dopamine and Its Connection to Microbial Presence
_Lactobacillus plantarum PS128_, for instance, has been found to mitigate dopaminergic neuronal death and oxidative stress in Parkinson's disease (PD) mouse models, potentially through modulation of dopamine metabolism and neurotransmitter activity [76]. _Clostridium_ species exhibit complex effects on dopamine metabolism. While certain species, like _Clostridium butylcium_, can increase hypothalamic dopamine concentrations, others, like _Clostridium tetani_, have been shown to metabolise dopamine into inactive forms, leading to oxidative stress and neurodegeneration. Nevertheless, Clostridia's ability toconjugate dopamine-like substrates into fatty acid amides, stimulating GPCR signalling, suggests both pathogenic and homeostatic effects on dopamine regulation [75]. _Enterococcus faecium_ and _Enterococcus faecalis_ have been identified as capable of converting L-dopa into dopamine in the gut, offering potential therapeutic implications for neurodegenerative disorders like PD. These species' enzymatic activities in dopamine synthesis underscore their importance in gut-brain communication and neurotransmitter regulation. _Ruminococcus_, a _Firmicutes_ genus, has been associated with both positive and negative effects on dopaminergic pathways. While _Ruminococcus_ species produce short-chain fatty acids (SCFAs) [77] with neuroprotective effects, mucin degradation and inflammation caused by certain _Ruminococcus_ strains can lead to dopaminergic neurodegeneration. Moreover, dysregulation in _Ruminococcus_ abundance has been implicated in tic disorders and Parkinson's disease, potentially influencing dopamine receptor expression and motor symptoms [78]. In summary, the gut microbiota's diverse composition and metabolic activities profoundly affect dopamine regulation, offering promising avenues for understanding and treating neurological disorders. 2.3 Microbial Contributions to Neurotransmitter Dynamics: Exploring the Gut-Brain Axis through Glutamate and GABA  
Gamma-aminobutyric acid (GABA), a crucial inhibitory neurotransmitter in the mammalian central nervous system (CNS) [79], is pivotal in the bidirectional communication between the gastrointestinal tract and the brain. This neurotransmitter can be also produced by the decarboxylation of L-Glutamate (Glu) catalysed by glutamate decarboxylase (GAD). The Gad genes in _Lactobacillus_ and _Bifidobacteria_ strains encode glutamate decarboxylase, facilitating GABA synthesis [80]. Various bacterial strains, including _Coryneform_ bacteria such as _Corynebacterium glutamicum_, _Brevbacterium lactofermentum_, and _Brevbacterium flavum_, can produce Glu [81]. Identification of GABA-binding proteins, including transporters (e.g., GabP in _E. coli_ and _Bacillus subtilis_) and possible specific receptors, support bacterial communication involving GABA. The physiological complexity of Glu and GABA extends beyond bacterial interactions to their crucial roles as major excitatory and inhibitory neurotransmitters in the human CNS. These compounds contribute to a homeostatic neuronal circuit involving intricate feedforward and feedback neuronal connections, managing the equilibrium among excitatory (Glutamatergic) and inhibitory (GABAergic) neurons [82]. Glu and GABA, along with glutamine, are integral components of neurotransmitter recycling in the brain [83]. In the context of gut microbiota, studies have reported the modulation of host Glutamate/GABAergic systems by GABA/Glu-producing bacteria. Notably, a GABA-producing _Bifidobacterium dentium_ has demonstrated the attenuation of sensitivity in dorsal root ganglia neurons in a rat model of visceral pain, shedding light on the potential impact of the gut microbiota on the host nervous system [84]. GABA's involvement in appetite control is evident, with disruptions in GABA signalling pathways linked to inhibited post-weaning feeding, blunted NPY-induced hyperphagia, and reduced hunger-induced appetite [85; 86]. GABA acts as a molecular signal influencing gastrointestinal motility and the secretion of appetite-related hormones.