A mass of animal and human data has linked increased fibre intake to metabolic benefits including weight loss, and the prevention of obesity and type 2 diabetes. However, the mechanisms behind these potential benefits have, until now, remained a mystery.
Writing in Cell, a French research team led by Gilles Mithieux of INSERM investigated whether these positive metabolic effects were related to the capacity of the intestine to produce glucose (known as intestinal gluconeogenesis - IGN) by giving rats and mice a variety of diets enriched with fermentable fibres or propionate or butyrate - which are short chain fatty produced by the gut when bacteria break down fibres.
By monitoring the expression of genes and enzymes responsible for the synthesis of glucose in the intestine Mithieux and his colleagues identified that the short-chain fatty acids (SCFAs) propionate and butyrate both activate IGN - but by different and complementary mechanisms.
"Butyrate activates IGN gene expression through a cAMP-dependent mechanism, while propionate, itself a substrate of IGN, activates IGN gene expression via a gut-brain neural circuit involving the fatty acid receptor FFAR3," wrote the French team.
They added that mice fed a fat and sugar-rich diet, but supplemented with fibres, became less fat than control mice and were also protected against the development of diabetes due to significantly increased sensitivity to insulin.
Mithieux and his team noted that the intestine is capable of producing glucose and releasing it into the blood stream between meals and at night. The production of glucose in the intestine is detected by the nerves in the walls of the portal vein (which collects the blood coming from the intestine) which in turn sends a nerve signal to the brain.
In response, the brain triggers a range of protective effects against diabetes and obesity: the sensation of hunger fades, energy expenditure at rest is enhanced and, last but not least, the liver produces less glucose, the team explained.
Making the link
In order to make the connection between fermentable fibres and the production of glucose by the intestine, the researchers subjected rats and mice to diets enriched with either fermentable fibre, propionate or butyrate.
The team found a strong induction of the expression of genes and enzymes responsible for the synthesis of glucose in the intestine from all three diets - however the molecular mechanisms behind the production of glucose were found to differ between propionate and butyrate.
After realising that the two fatty acids had potentially complimentary mechanisms the team then repeated their experiment with mice whose intestine's ability to produce glucose had been suppressed by genetic engineering - and found that none of the protective effects associated with fibre intake could be observed. Instead, these mice became fat and developed diabetes like those fed a fibre-free diet.
This finding led the French team with only one conclusion: It is the production of glucose by the intestine from propionate and butyrate that is behind the positive effects of fibre consumption.
"The regulation of IGN is necessary for the metabolic benefits associated with SCFAs and soluble fibre," they said.
Published online ahead of print, doi: 10.1016/j.cell.2013.12.016
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