Bacterial components and their effect on energy metabolism in human skeletal muscle cells

Obesity and type 2 diabetes are associated with changes in gut microbiota and disturbed energy metabolism. We hypothesize that there is a crosstalk between gut bacteria and host energy metabolism.

We study the effect of various bacterial products on skeletal muscle cell metabolism. 

The gut microbiota has gained much focus in recent years, and it has been documented that the bacterial composition of the gut flora in obese individuals is different to that in lean ones. 

Similarly, there are differences in the microbiota of type 2 diabetics vs. non-diabetics. The gut wall can become leaky from a high-fat diet, and thus bacteria as well as bacterial products might reach the circulation. 

Bacteria-derived substances, such as vitamins, are essential to us, whereas other substances, such as pro-inflammatory mediators, are harmful. 

In the present project, effects of various bacterial products on energy metabolism are explored. The direct effect of pro-inflammatory mediators and bacterial metabolites on skeletal muscle cells is studied. 

Little is known about this field, and we are in the early stages of understanding the complex interplay between human gut microbiota and health.

The understanding of this system can potentially open completely new ways of treating obesity and type 2 diabetes.

  • Participants

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  • More about the project

    The gut microbiota has recently gained much focus. The composition of gut microbiota is different in obese individuals compared to that in lean ones, and it can be changed by a high-fat diet. 

    The gut microbiota-derived lipopolysaccharide (LPS) is probably a key molecule linking the gut microbiota to host metabolism and low-grade inflammation. 

    Elevated plasma LPS concentrations have been found in obese and type 2 diabetic subjects, and a high-fat meal increased plasma LPS concentrations in both healthy and type 2 diabetic subjects.

    Injection of LPS into healthy subjects induced insulin resistance, and furthermore the addition of LPS to human skeletal muscle cells in culture impaired insulin signaling and modulated energy metabolism. 

    However, the changes in gut microbiota are not solely associated with Gram-negative bacteria, as the Gram-positive genus  Clostridium (belonging the phylum Firmicutes) for example  has been found to be more abundant in type 2 diabetic subjects than in pre-diabetic and subjects with normal glucose tolerance.

    This implies that other factors than LPS might be important in the crosstalk between gut bacteria and the host’s energy metabolism. Bacterial metabolic products, such as short chain fatty acids might play a role both as an energy source in the body and as possible signaling factors. 

    Other bacterial components such as proteoglycans, flagellin, and acidic polysaccharides might participate. 

    Research questions and methodology

    The overall aim of the present project is to evaluate the effect of bacterial components on energy metabolism in human skeletal muscle cells. Skeletal muscle cells are isolated from human biopsy samples, bacterial products are added to skeletal muscle cell cultures and cellular metabolism are studied.

    Areas of current research related to the main project:

    • The effect of Toll like receptor (TLR) ligands on glucose and fatty acid metabolism in human skeletal muscle cells.
    • The effect of lactic acid, a derivate of bacterial metabolism, on skeletal muscle cells.
    • The effect of short chain fatty acids (SCFA), bacterial metabolites formed by gut fermentation of prebiotics, on skeletal muscle cells.
    • The effect of branched chain fatty acids (BCFA), fatty acids formed by ruminant bacteria, on skeletal muscle cells.