# 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  
Manipulation of the gut microbiome composition, for instance, through probiotic administration or faecal microbiota transplant, has been demonstrated to induce changes in brain activity and cognitive behaviour by modulating neurotransmitter activity, with dopamine receiving notable attention [61; 62]. Neurons within the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNpc) of the midbrain regulate dopamine, a crucial element in both the gastrointestinal (GI) tract and CNS [63]. Essential components for dopamine functions are the dopamine transporter (DAT) and dopamine receptors (D1-D5), influencing various physiological processes [64; 65]. The gut microbiome modifications link to alterations in the expression of these components. Specific microbial genera, including _Prerotella_, _Bacteroides_, _Lactobacillus_, _Bifidobacterium_, _Clostridium_, _Enterococcus_, and _Ruminococcus_, have been shown to modulate receptors, transporters, and targets of the dopaminergic pathway [65; 66; 67; 68]. Despite several studies highlighting the connections between microbes and dopaminergic pathways in the CNS and the GI system, the underlying mechanisms still need to be completed. Disrupted homeostasis of the healthy intestinal flora has been correlated with several pathological conditions, including neurological disorders like Parkinson's disease, attention deficit hyperactivity disorder (ADHD), depression, anxiety, and autism [69]. It remains unclear whether alterations in the gut microbiota result from faulty brain signalling or whether they can drive brain disorders. Alterations in neurotransmitters, such as decreased dopamine concentrations, have been associated with the aetiology of neurodegenerative disorders. These neurotransmitters activate nerve ganglia in the enteric nervous system (ENS), playing a crucial role in the gut-brain axis by transducing luminal stimuli to the CNS through the vagus nerve [70]. Microbes can interact directly with the CNS through actions in the GI tract, such as serotonin secretion into the lamina propria [71] or translocation of metabolites and endotoxins from the intestinal lumen to the circulation. Signals such as hormones, nutrients, and peptides produced by intestinal microbes also activate vagal afferents, highlighting the multiple mechanisms through which alterations in gut microbial species and their metabolites can modulate afferent vagal nerve activity [55; 72]. Notably, the vagus nerve is a primary mediator in the gut-brain crosstalk, influencing central and peripheral dopamine concentrations. Evidence has shown that vagal nerve stimulation induces dopaminergic activation, impacting dopamine concentrations in the CNS [73]. Rodent models undergoing vagotomy have documented the importance of vagal communication between the ENS and CNS, revealing hampered regulation of neurogenesis and decreased expression of brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. BDNF is recognised for its neuroprotective effects against dopamine neuron degeneration [74]. _Prerotella_ and _Bacteroides_ influence dopaminergic pathways by producing metabolites that affect dopamine functioning and synaptic activity. For example, _Bacteroides uniformis_ administration has been associated with increased striatal dopamine transporter (DAT) binding. _Prerotella copri_ abundance is inversely correlated with DAT binding, suggesting a role in modulating dopaminergic tone. _Prerotella_ is also linked to elevated plasma ghrelin levels, indirectly influencing dopamine recruitment through the ventral tegmental area (VTA) [75]. Probiotic genera like _Lactobacillus_ and _Bifidobacterium_ have shown promise in reducing depression- and anxiety-like behaviours, regulating stress responses, and alleviating symptoms in dopamine-related neurological disorders.