Gut reactionTaking it over at the Dana centreThe Dana Centre in the new Wellcome Wolfson Building will create a space devoted to public debate and discussion. |
People used to think the colon was largely a storage place for waste material waiting to be excreted," says Professor Jenny Ames at the University of Reading. "But in recent years, micro-biologists, nutritionists and clinicians and have come to recognise the important and active role the colon plays in health and disease."
This understanding was born of the realisation that the human colon is home to millions of bacteria. "More bacteria live in our gut than we have cells in our body, and many are still being discovered," says Professor Ames. "Everything that survives the body's digestive machinery and passes to the colon is potentially food for these bacteria, which ferment and absorb it. As a result, the colon is actually the most metabolically active area in the human body."
The products of fermentation by bacteria can have various effects on the human body, depending on the components of the waste material and the type of bacteria reacting with it. "Some bacteria are beneficial, and their fermented products promote health, while others are detrimental and produce toxins."
The sheer number of bacteria resident in the gut and their high level of reactivity with the waste material passing through make the colon a prime site for many bacterial infections, causing, among other things, acute gastroenteritis, bowel cancer, or ulcerative colitis, a chronic inflammatory disease, affecting one in 10 000 people.
Professor Ames and her colleagues, Professors Glenn Gibson and James Crabbe, are investigating how bacteria react with different proteins in human faeces in the colon to find out which foods are likely to promote inflammation in patients with ulcerative colitis.
To date, research into bacteria in the colon has tended to concentrate on their reactions with carbohydrates, but Professor Ames and colleagues will be focusing on their response to proteins, especially proteins that have been 'glycated'. "A glycated protein is a protein that has reacted with a sugar," explains Professor Ames. "Because most of the food we eat is heated, glycated proteins are widespread in our diet, for example, in bread, milk and meat. At a molecular level, what happens during glycation is that sugar molecules attach themselves to the protein's chain of amino acids. Some of the bacteria in the colon can degrade these glycated proteins, and we want to find out whether that process causes inflammation of the gut tissue."
The first study, which will be undertaken in collaboration with Royal Berkshire Hospital, is a human feeding trial investigating the effects of different diets on two groups of six volunteers - one group with ulcerative colitis and the other without. Each group will spend two weeks eating a heavily heat-processed diet (toast, the crusts of bread, well-cooked meat), and another two weeks eating a lightly heat-processed diet, (untoasted bread without the crust, less well-cooked meat). Faeces samples will be taken from all the volunteers at the start and end of each diet.
At the end of the study, the faeces will be studied to establish which bacteria have grown as the result of interacting with a particular protein. Samples will be sent to a collaborator in Germany, Dr Veronika Somoza at the Federal Research Institute of Food Chemistry in Garching, whose laboratory has the technical expertise to assess whether the products of bacterial fermentation promote inflammation.
The second study involves using models of the human colon, an elaborate series of faeces-filled pipes, tubes and vats. These are inoculated with faeces from people with and without ulcerative colitis. Glycated proteins, in the form of bovine serum albumin (BSA) or toast, are then passed through the model guts.
In parallel experiments, glycated proteins will be sent to the Department of Chemistry and Biochemistry at the University of South Carolina, USA, where Professor John Baynes and colleagues will carry out chemical analyses to determine exactly what structural modifications occurred to the protein during glycation before it was used in the gut model experiments "We use BSA in the model gut, because the protein has a known amino acid sequence and has been well characterised," explains Professor Ames. "Professor Baynes will be looking at where exactly the sugar attaches to the amino acid during glycation and which forms of glycated proteins affect the growth of bacteria that produce toxins."
Ultimately, Professor Ames hopes this research will produce greater understanding of the dietary factors that cause inflammation in the gut, and thereby help alleviate the discomfort associated with ulcerative colitis. "We want to be able to offer people guidance, such as whether or not it's wise to eat a diet that has been highly heat-processed if you've got ulcerative colitis, or what kinds of proteins to eat, so that they can live as healthy and comfortable a life as possible."
External links
- Professor Jenny Ames at the School of Food Biosciences, University of Reading: Research interests
Project collaborators:
- Food Microbial Sciences Unit at the University of Reading: Affiliation of Professor Glenn Gibson
- Animal and Microbial Sciences at the University of Reading
- Wolfson Laboratory at the University of Reading: Affiliation of Professor James Crabbe
- Professor John Baynes in the Department of Chemistry and Biochemistry at the University of South Carolina, USA: Research interests
- Dr Veronika Somoza at the Federal Research Institute of Food Chemistry, Garching, Germany: Research interests
Further reading
Brock J W, Hinton J S, Cotham W E, Metz T O, Thorpe S R, Baynes J W and Ames J M. (2003) Proteomic analysis of the site specificity of glycation and carboxymethylation of ribonuclease. J. Proteome Research, In press.
Hinton D J S and Ames J M. (2002) Analysis of glycated protein by capillary electrophoresis. In: 'The Maillard Reaction in Food Chemistry and Medical Science: Update for The Postgenomic Era'. Horiuchi S, Taniguchi N, Hayase F, Kurata T and Osawa T (eds). Excerpta Medica International Congress Series 1245, Elsevier, Amsterdam. pp. 471-74.
Rastall R A, Fuller R, Gaskins H R and Gibson G R. (2000) Colonic functional foods. In: 'Functional Foods: Concept to Product'. Gibson G R and Williams C M (eds). Woodhead Publishing Limited, Cambridge. pp. 72-95.
Steer T, Carpenter H, Tuohy K and Gibson G R. (2000) Perspectives on the role of the human gut microbiota and its modulation by pro- and prebiotics. Nutrition Research Reviews 13: 229-54.
Rembacken B J, Snelling A M, Hawkey P M, Chalmers D M and Axon A T. (1999) Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomized trial. Lancet, 354: 635-39.
Shanahan F. (2000) Probiotics and inflammatory bowel disease: is there a scientific rationale? Inflammatory Bowel Disease 6: 107-15.

