Figure 6.

Microbial metabolites that affect glucose tolerance and inflammation. (1) A high fiber consumption has several beneficial effects on the gut microbiota and host health. They are degraded by the gut microbiota in short chain fatty acids such as butyrate, propionate, and acetate. SCFAs can be taken up by the enterocytes, used as an energy source or bound to free fatty acid receptors to stimulate varies responses (e.g., GLP-1 release from intestinal L-cells). Intracellularly, it can stimulate epigenetic changes via histone deacetylase (HDAC). It supports the expansion of beneficial bacteria and keeps opportunistic pathogens in control, improves glucose and appetite control, supports intestinal barrier integrity and induces an anti-inflammatory immune response in intestinal as well as systemic tissue sides. (2) Primary bile acids (pBA) are produced in the liver from cholesterol and secreted into the intestine via the gall bladder. There, they can change the gut microbiota and are transformed by bacteria to secondary bile acids (sBA). Bile acids can activate intestinal and systemic TGR5 as well as FXR, which increases the energy expenditure, lower inflammation and improves glucose tolerance. (3) A westernized diet, which is usually rich in saturated lipids, can disturb the branched chain amino acid (BCAA) catabolism of the host, which in turn inhibits the insulin signaling. (4) Further, a westernized diet is commonly rich in choline and carnitine, which the gut microbiota can metabolize to trimethylamine (TMA). After intestinal uptake, the liver transforms TMA into Trimethylamine N-oxide (TMAO) via flavin-containing monooxygenase (FMO). TMAO inhibits bile acid synthesis, reverse cholesterol transport (RCT), induce macrophage foam cell formation and inflammation via NLRP3. That in turn leads to cardiovascular complications.