Figure 5.

Molecular mechanisms linking gut microbiota and host health in both healthy and pathological situations. In healthy situations, colonocytes use butyrate as an energy substrate through beta-oxidation in the mitochondria. This process consumes oxygen and helps maintain an anaerobic condition in the lumen. Additionally, butyrate binds to peroxisome proliferator-activated receptor gamma (PPARγ), which represses inducible nitric oxide synthase (iNOS), leading to a decrease in nitric oxide (NO) and nitrate production. Glycolysis increases, oxygen consumption lowers, and PPARγ activity decreases in pathological conditions with low butyrate levels in the lumen. Consequently, iNOS expression increases, leading to more NO production and an increased availability of nitrates for specific pathogens. Furthermore, butyrate can stimulate regulatory T cells (Treg) to reduce inflammation. In healthy colonocytes, the nuclear transcription factor aryl hydrocarbon receptor (AhR) is extensively expressed and active. The function of the intestinal barrier can change as a result of decreased AhR activity or agonist deficit. SCFAs, particularly endocannabinoids (eCBs), and BAs all activate a number of important receptors that are expressed by enteroendocrine cells (L-cells). The activation of these receptors increases the secretion of important gut peptides like GLP-1, GLP-2, and PYY. Together, the interactions between these molecular players and gut bacteria help to prevent metabolic endotoxemia and hepatic steatosis, decrease intestinal permeability, and increase insulin secretion and sensitivity. They also help people eat less and have lower plasma lipid levels. There is a correlation between all of these effects and less inflammation. On the other hand, opposing effects have been seen under pathological circumstances.