Axes of host gut microbiota metabolic interactions.

Axes of host gut microbiota metabolic interactions.

A host-microbe metabolic axis can be defined as a multidirectional interactive chemical communication highway between specific host cellular pathways and a series of microbial species, sub-ecologies, and activities. Examples of such axes include bile acid production, where bile acids metabolized by gut microbes, especially lactobacilli, bind to host nuclear receptors involved in a variety of cellular processes. The endocannabinoid system is modulated by microbially generated molecules such as lipopolysaccharide that alter gut permeability and signaling to the brain. The aromatic acid axis links metabolically active molecules such as cresols and amines (which are vasopressors) generated by colon microbes like clostridia to the host’s ability to sulfate drugs such as acetaminophen. Short-chain fatty acids such as n-butyrate (formed from gut fermentation of complex carbohydrates in the proximal colon) provide an energy source for colon microbes but are also pharmacologically active, inducing angiogenesis in the gut mucosa. A diverse range of neurochemically active species (neurotransmitter axis) are produced by gut microbes ranging from γ-aminobutyrate to hydrogen sulfide and other gasotransmitters, which modulate ion transport and the enteric nervous system locally in the gut. The microbial-specific conversion of dietary choline to trimethylamine can also generate potentially toxic species that have been associated with atherogenesis and nonalcoholic fatty liver disease in mice. Collectively, these notional host-microbe metabolic axes provide potential targets for therapeutic intervention at different stages in life.