# Microbes in Health and Disease: Human Gut Microbiota
## 3 Multifunction of the Human Gut Microbiota  
As illustrated in Figures 3 and 4, the gut microbiota plays various important roles in (i) digestion and metabolism [59; 60]; (ii) colonization resistance against pathogens [61]; (iii) intestinal epithelial homeostasis related to the differentiation and proliferation of the intestinal epithelium; (iv) the development, education, and regulation of immunity; and (v) the development and function of the central nervous system [27], etc. These are further discussed below.  
Figure 3: Illustration of the roles of gut microbiota (**I**) in digestion and metabolism, where certain members of gut microbiota are able to digest carbohydrates (indigestible for human) to short-chain  
fatty acids (SCFAs) that serve as important energy sources for colonocytes, regulators of immunity, inflammation, metabolism, etc. The gut microbiota can also produce vitamins and participate in the biosynthesis of secondary bile acids. (**II**) In colonization resistance, the gut microbiota resists against the colonization of pathogens via multiple mechanisms associated with the production of antimicrobials, the production of inhibitive compounds (e.g., secondary bile acids that inhibit the germination of _Clostridioides difficile_), the formation of a physical barrier against the proliferation of pathogens, and inducing the immune system to secrete IgA against pathogens. (**III**) In intestinal epithelia homeostasis, for example, SCFAs produced by certain members of gut microbiota not only serve as the energy source of colonocytes but also maintain the structural and functional integrity of physical and chemical barriers of intestinal epithelium. (**IV**) In the development and regulation of immunity, for example, segmented filamentous bacteria among gut microbiota attach to and trigger the epithelium to secrete serum amyloid A. Serum amyloid A is further involved in the differentiation of Th17 cells and the production of Th17 effector cytokines (e.g., IL-17 and IL-22) that are associated with increased resistance against pathogen _Citrobacter redontium_. SCFAs are involved in the differentiation of T cells into regulatory T cells (e.g., Tregs) and effector T cells (e.g., Th1 and Th17 cells).  
Figure 4: Illustration of the human gut microbiota, intestinal epithelium, host immunity, and gut-microbiota–brain axis. Gut microbes can produce various antimicrobials and neurotransmitters (e.g., gamma-aminobutyric acid (GABA) and serotonin), and the human gut microbiota is also involved in the metabolism of tryptophan, which is the precursor of serotonin. The bidirectional gut–brain axis comprises the central nerve system, autonomic nerve system, urepresent, hypothalamic–pituitary–adrenal (HPA) axis, circulatory system, immune system, as well as the gut microbiota and involves neuronal, endocrine, and immune pathways. It is hypothesized that the gut microbiota can affect the HPA axis via multiple microbe-associated signals. These stressors or signals stimulate the neurons of the paraventricular nucleus of the hypothalamus to secrete corticotropin-releasing hormone (CRH); subsequently, the CRH is transported and triggers the pituitary gland to release adrenocorticproline hormone (ACTH), which further stimulates the production and secretion of cortisol in the adrenal glands. Cortisol has multiple roles (e.g., regulating metabolism and neuroimmune signaling).