Functions of Gut Microbiota Metabolites, Current Status and Future Perspectives

Abstract

Gut microbiota, a collection of microorganisms that live within gastrointestinal tract, provides crucial signaling metabolites for the physiological of hosts. In healthy state, gut microbiota metabolites are helpful for maintaining the basic functions of hosts, whereas disturbed production of these metabolites can lead to numerous diseases such as metabolic diseases, cardiovascular diseases, gastrointestinal diseases, neurodegenerative diseases, and cancer. Although there are many reviews about the specific mechanisms of gut microbiota metabolites on specific diseases, there is no comprehensive summarization of the functions of these metabolites. In this Opinion, we discuss the knowledge of gut microbiota metabolites including the types of gut microbiota metabolites and their ways acting on targets. In addition, we summarize their physiological and pathologic functions in health and diseases, such as shaping the composition of gut microbiota and acting as nutrition. This paper can be helpful for understanding the roles of gut microbiota metabolites and thus provide guidance for developing suitable therapeutic strategies to combat microbial-driven diseases and improve health.

Keywords: circadian rhythm; energy metabolism; gut microbiota metabolites; immune response; intestinal barrier; short-chain fatty acids.

Figure 1.

Ways gut microbiota metabolites act on targets. Within gut lumen, gut microbiota metabolites serve as the nutrients for some bacteria and change the composition of gut microbiota. Locally, gut microbiota metabolites can act on intestinal epithelium and immune cells in the lamina propria, and the local effects can further induce downstream systemic functions. Systemically, gut microbiota metabolites can be absorbed and transported to remote organs and tissues to exert diverse functions. Some gut microbiota metabolites can indirectly regulate the composition and function of gut microbiota via inducing hosts to synthesize and release anti-bacterial materials into gut lumen. Some gut microbiota metabolites may undergo enterohepatic circulation.

Figure 2.

Typical gut microbiota metabolites in modulation of host metabolism. The major ways of this modulation include regulation of nutrition metabolism (lipids, proteins, glucose), non-shivering thermogenesis (browning of WAT and BAT), satiety (by secretion of hormone GLP-1 and PYY), motility function of organs (muscle and heart), insulin synthesis and secretion, and insulin sensitivity. By these ways, gut microbiota metabolites can maintain the homeostasis of energy.

Figure 3.

Gut microbiota metabolites modulation of intestinal barrier. Intestinal barrier consists of microbial barrier, chemical barrier, physical barrier, and immune barrier. SCFAs can enhance the chemical barrier by stimulating the secretion of antimicrobial peptides, sIgA and mucins to prevent harmful bacteria. SCFAs, bile acids, and indole derivatives can enhance physical barrier via increasing tight junction proteins such as cludins, occluden-1, and occludin. The epithelial cross of SCFAs and indole derivatives can act on immune cells and lead to release of anti-inflammatory cytokines such as IL-10 and IL-22. During chronic diseases, disturbance of tights junctions can lead to destruction of physical barrier, and further lead to translocation of LPS and bacteria. This translocation triggers the activation of immune cells and lead to production of pro-inflammatory cytokines. The release of pro-inflammatory cytokines can act on local epithelial cells to worsen physical barrier or can act on extraintestinal organs to trigger other diseases.

Figure 4.

Gut microbiota metabolites modulate the nervous system and circadian rhythm. Gut microbiota metabolites can modulate the cerebral inflammation, the production of gut hormones, the transmission of nervous impulse, the functions of blood-brain barrier to regulate the functions of brains such as the emotion and appetite. On the contrary, the brain can modulate the functions of gut such as the gut motility and secretion of digestive juice. The production of gut microbiota metabolites shows day-night rhythm, and this rhythm can be transported to the central clocks and peripheral clocks to modulate the systemic functions of hosts. Similarly, the central clock can transfer the light and dark cues to peripheral organs and gut microbiota, and thus synchronize the functions of gut microbiota and host clocks.