# Gut Microbiota as an Endocrine Organ: Unveiling Its Role in Human Physiology and Health
## 4 Gut Microbiota Metabolites and Hormonal Alterations in Human Physiology  
As discussed earlier in this article, researchers have explored the endocrine aspect of gut microbiota and its implications for modulating various physiological processes. In addition to producing and secreting hormones, gut microbiota also responds to host hormones and regulates the expression levels of host hormones. As highlighted earlier, the burgeoning field of microbiome research has revealed that microbes within multicellular hosts exert significant influence over metabolism, immunity, and behaviour. While researchers are just beginning to answer essential questions regarding the mechanisms underlying these microbial effects on specific host characteristics, emerging evidence suggests that hormones play a pivotal role in mediating these interactions. While researchers have yet to decipher the precise pathways of microbiota-based hormonal signalling, it is evident that the presence and activity of gut microbiota correlate with specific alterations in hormone levels. Expanding upon this understanding, researchers further explore the intricate relationship between gut microbiota metabolites and hormonal alterations in the human body, with implications for stress management, immunity, sex hormones, appetite regulation, and metabolism. Microbial Metabolites and Appetite Regulation: Insights and Implications for Therapeutic Interventions  
The sensations of hunger and satiety are fundamental involuntary drivers of feeding behaviour in both humans and animals [114, 115, 116]. Appetite, a process controlled by the central nervous system (CNS), comprises short-term signals from gastrointestinal hormones regulating food intake and long-term signals from adipose tissue reflecting energy stores and environmental cues. The intricate appetite system, involving the CNS, hormones, and vagal afferents, initiates or inhibits food intake. Dysregulation of appetite can lead to eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN), as well as metabolic diseases like obesity, posing significant threats to human health [117]. Accumulating evidence supports the profound influence of gut microbiota on eating behaviour in humans and animals. Alterations in gut microbiota accompany eating disorders, with AN patients exhibiting lower faecal microbial \(\alpha\)-diversity and different bacterial compositions, while BN patients show a higher abundance of bacterial ClpB protein [118]. Furthermore, changes in gut microbial communities affect appetite and feeding behaviour, as seen in a piglet model where lysine-restricted microbial communities correlated with reduced circulating satiety hormones and increased feed intake [119, 120]. The gut microbiota and the appetite system are closely linked, with energy metabolism and microbial metabolites serving as potential mechanisms. Microbiota-derived metabolites, including GABA, BAs, and SCFAs, may influence host metabolism and appetite [121]. Gut microbiota alterations affect appetite-related hormones (leptin, ghrelin, and insulin), which modulate brain behaviour and function via humoral or neural pathways. Leptin, primarily secreted by white adipose tissue, reflects the body's energy stores and acts on anorexia neurons in the hypothalamic arcuate nucleus to inhibit appetite [122, 123]. Gut microbiota abundance and richness are associated with leptin signalling, and microbiota depletion affects leptin signalling and food intake in mice. Probiotics or prebiotics supplementation can affect leptin signalling and food intake in obese mice [124, 125]. Ghrelin, a hunger hormone mainly produced by the stomach, transmits starvation signals to the brain and is influenced by gut microbiota. Prebiotic administration inhibits feed intake by enhancing GLP-1 and PYY synthesis and inhibiting ghrelin production [126], although results may vary depending on the intervention and population. Insulin regulates glucose and energy homeostasis, functions as a satiety signal, and is influenced by gut microbiota.