Abstract
"We show that the gut bacterial metabolites, short chain fatty acids (SCFAs), are present at exceptionally high concentrations in the portal venous circulation, particularly small blood vessels that emanate from colonic mucosa. Likely, many other metabolites will be present at high concentrations. Herein we propose a model for immune conditioning, whereby metabolites such as butyrate affect immune cells as they pass through the portal venous system. Deficiency of SCFA would lead to pro-inflammatory immune cell skewing through insufficient G-protein coupled receptor (GPCR) signalling, or lack of histone deacetylase (HDAC) inhibition. Such pro-inflammatory immune cells may travel to tissues such as the brain, the lung, the kidney etc and promote disease. This model helps explain how the gut microbiome may be affecting peripheral immune cells, and consequently Western lifestyle diseases, most of which are immune based, in tissues remote from the gut."