Gut metabolites and LPS
The aim of the project is to investigate how gut metabolites formed from colonic fermentation of indigestible components in vegetable food items affect metabolic risk parameters in blood associated to the metabolic syndrome. Special focus will be on short-chain fatty acids and their effect on metabolic risk markers, bile acid metabolism, levels of LPS (lipopolysaccharides) in blood and gene expression for lipopolysaccharide signalling.
Low-grade inflammation is associated with obesity, insulin resistance and diabetes type 2, and is caused by LPS, present in the outer cell-walls of gram-negative bacteria. The term LPS is often used interchangeably with endotoxin, but it is the lipid component in the LPS that is held responsible for the toxicity.
An impaired nutritional condition of the colonic mucosa may increase the permeability of the intestinal wall and the influx of proinflammatory substances such as LPS. However, components in the diet may stimulate the mucosal proliferation and reduce the mucosal permeability. Short-chain fatty acids (SCFA), especially butyric acid, formed from microbial degradation of dietary fibre in our diet, and as recently also suggested the bacterial metabolites formed from certain phytochemicals e.g. polyphenols are examples of such products. However, when studying events in the colon it is also important to register toxic metabolites formed, such as certain primary and secondary metabolites from amino acid fermentation. The composition of the colon microbiota is of great impact in this respect, which can be changed either by probiotics (beneficial bacteria) or prebiotics (fermentable dietary components). Bile acids are factors that regulate the composition of the colon microbiota, or vice versa, and the transformation to secondary bile acids is dependent on the diet.
Project leader: Professor Margareta Nyman