Altering bugs in the gut could tackle non-alcoholic fatty liver disease and other conditions linked to insulin resistance

For immediate release
Friday 18 August 2006

Altering the makeup of bugs in the gut could be a way of tackling insulin resistance and related problems such as non alcoholic fatty liver disease, according to new research published this week.

The study also has implications for the treatment of associated conditions such as type 2 diabetes, obesity and heart disease.

The research shows that the type of microbes found in the guts of mice with a certain genetic makeup causes them to be pre-disposed to insulin resistance and non-alcoholic fatty liver disease (NAFLD). On a high fat diet, these microbes transform the nutrient choline, found in food and essential for metabolising fat, into methylamines.

Scientists believe that these methylamines, which can only be produced by the microbes in the gut, lead to insulin resistance. In addition, because choline is needed to transport fat out of the liver, altering choline metabolism leads to fat accumulating in the liver and NAFLD.

The researchers are hopeful that their results in mice mean that they could intervene to change the makeup of gut microbes in people, to prevent their microbes from changing choline into methylamine. This would greatly reduce a person's chances of becoming insulin resistant, developing NAFLD or suffering from associated problems.

The research is published this week in the Proceedings of the National Academy of Sciences by researchers from Imperial College London and the Wellcome Trust Centre for Human Genetics, University of Oxford.

Professor Jeremy Nicholson , senior author of the paper from Imperial College London, said: "It has been known for some time that a person's genetic makeup can make them pre-disposed to insulin resistance and associated conditions. Finding out how this pre-disposition is linked to microbes in the gut offers us the prospect of tackling major health problems in people by intervening to change the makeup of these microbes. This is much more feasible than altering a person's genetic makeup."

The researchers measured the plasma and urine of two genetic strains of mice using nuclear magnetic resonance spectroscopy and computer modelling. One strain had a genetic predisposition to insulin resistance and NAFLD whilst the other strain did not.

The authors conclude their study provides more evidence that complex metabolic diseases are the product of the human and bacterial genomes as well as diet and lifestyle.

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For further information please contact:

Laura Gallagher
Press Officer
Communications Division
Imperial College London
Tel: +44 (0)20 7594 6702
Email: l.gallagher@imperial.ac.uk

Notes to editors:

1. "Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice" Proceedings of the National Academy of Sciences, August 15 2006

Marc-Emmanuel Dumas(1)*, Richard H Barton(1), Ayo Toye(3), Olivier Cloarec(1), Christine Blancher(3), Alice Rothwell(3), Jane Fearnside(3), Roger Tatoud(2), Veronique Blanc(2), John C Lindon(1), Elaine Holmes(1), Mark I McCarthy(3), James Scott(2), Dominique Gaugier(3), Jeremy K Nicholson(1)(2)*

(1) Department of Biological Chemistry, Imperial College London
(2) Genetics and Genomics Research Institute, Imperial College London
(3) Wellcome Trust Centre for Human Genetics, University of Oxford
* Corresponding authors

2. About non-alcoholic fatty liver disease (NAFLD)
NAFLD is a fatty inflammation of the liver related to insulin resistance that in its most extreme form can cause cirrhosis. There is currently no standard treatment for the disease and patients are usually encouraged to try weight loss or insulin sensitisers to reduce its effects. It is estimated to affect between 10-27% of the world's population.

3. About Imperial College London
Consistently rated in the top three UK university institutions, Imperial College London is a world leading science-based university whose reputation for excellence in teaching and research attracts students (11,000) and staff (6,000) of the highest international quality.
Innovative research at the College explores the interface between science, medicine, engineering and management and delivers practical solutions that enhance the quality of life and the environment - underpinned by a dynamic enterprise culture.
Website: www.imperial.ac.uk

4. Imperial College London, in conjunction with Queen Mary and Westfield College London, Cambridge University and Oxford University was awarded a £5.4 million collaborative program grant funded by the Wellcome Trust (www.wellcome.ac.uk) Functional Genomics Development Initiative in 2002. The programme designated a Biological Atlas of Insulin Resistance (www.bair.org.uk) has been implemented by international investigators with expertise in insulin signalling, rodent genetics, human genetics, emergent '-omics' sciences (metabonomics, proteomics, transcriptomics), bioinformatics, and structural biology.