# 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
It also serves as an inhibitory neurotransmitter within the CNS, necessary for activating AgRP neurons [87]. Although the ability of GABA to cross the blood-brain barrier (BBB) remains inconsistent, studies predominantly focus on dietary GABA rather than endogenous GABA [88]. Rumen-protected GABA supplementation, known to increase feed intake and inhibit CCK signalling in growing lambs and cows, suggests a potential interaction with cholecystinin (CCK) through shared signal transduction pathways. This prompts the hypothesis that GABA may influence appetite control by acting on its receptors in the gastrointestinal tract and brain, subsequently affecting the secretion of gut hormones and activating central neurons [89]. Despite these insights, there is limited research on the relationship between gut microbial-derived GABA and appetite control. Further investigations are warranted to unravel the precise GABA role produced by the gut microbiota in shaping host metabolic health and to ascertain whether GABA can traverse the BBB, influencing the CNS to regulate appetite. The literature supports that GABA, originating from the microbiota, can influence host behaviour. For instance, the administration of _Lactobacillus humans_ to mice demonstrated alterations in GABA receptor expression, resulting in a reduction in anxiety- and depression-related behaviours [90]. Beyond bacterial interactions, Glu and GABA are prevalent in dietary sources and supplements, impacting human health. Glu, abundant in dietary proteins, and GABA, found in plant foods and fermented products, are ingested through various diets globally. Studies have reported positive effects of GABA supplementation on stress reduction and improved human cognitive function [91]. The pathways through which luminal Glu/GABA might affect the CNS would include transport across the intestinal barrier and BBB and interaction with receptors in the gastrointestinal tract. Transporters facilitating glucose absorption in the gastrointestinal epithelial cells, particularly in the small intestine, have been identified, and the glucose transport rate increases with higher intraduodenal glucose intake [92]. GABA transporters, predominantly found in the CNS, have also been detected in human intestinal epithelial cells, suggesting the potential for luminal GABA to cross the intestinal barrier and reach extra-intestinal targets. Studies have analysed that oral administration of GABA in rats increases GABA concentration in blood, indicating a potential pathway for GABA absorption [93]. Furthermore, various Glu receptor types, including metabotropic and ionotropic receptors, have been identified in GI epithelial cells and enteric neurons, implicating a role in luminal Glu sensing. Luminal Glu can influence defence mechanisms in the duodenal mucosa, suggesting a potential physiological impact on the GI tract [94]. Regarding GABA, GABA receptors are abundantly expressed in the GI tract and regulate gut motility and gut-to-brain signalling. The potential interaction between GABA and \(\mu\)-type opioid receptors has been reported, suggesting a modulatory role in anti-nociceptive action. Considering the broad distribution of GABA receptors in immune cells and their involvement in immunological processes, a role for GABA in neuro-immune communication within the gut is proposed [95]. As GABA is produced through Glu decarboxylation in both eukaryotes and prokaryotes, GABA-producing microorganisms in the gut may significantly influence the luminal Glu/GABA ratio, thereby affecting gut signalling. In conclusion, the bacterial production of Glu and GABA extends beyond their classical roles in the mammalian CNS, encompassing intricate interactions within the gut microbiota. These molecules, originating from both endogenous and dietary sources [41], have the potential to impact human health by influencing stress, cognitive function, and gastrointestinal processes.