Quantitative Analysis of Microbial Metabolism in the Human Large Intestine

Alvaro      Belenguer; Sylvia   H.   Duncan; Grietje      Holtrop; Harry   J.   Flint; Gerald   E.   Lobley

Abstract

Microbial metabolism in the human colon impacts on health and disease. Production of intermediate metabolites and end-products depends largely on the supply of dietary carbohydrates, including prebiotics (fructooligosaccharides) and functional foods (resistant starch), that resist small intestinal digestion. Colonic bacteria ferment these substrates to a wide range of products, predominantly short-chain fatty acids, including metabolites that can be either deleterious (e.g. D-lactate, sulphides) or beneficial (e.g. butyrate) to gut health. Lactate accumulation in the colon has been associated with gastrointestinal disturbance, for example in severe ulcerative colitis, whereas in the healthy state lactate is efficiently utilised by gut bacteria. Understanding the interaction between microbial metabolism and dietderived nutrient supply is crucial for maintaining a healthy metabolic balance in the colon. Prediction of such nutritional responses can be achieved by integrating in mathematical models information from stable isotope studies, that quantify metabolite flows, and molecular techniques, that accurately determine changes in microbial composition diversity. From such approaches, better nutritional advice can be provided in order to improve gut health. Furthermore, such understanding can be used to manipulate and improve the action of prebiotics and probiotics.

Keywords: Lactate, butyrate, microbial fermentation, bifidobacteria, stable isotopes, mathematical modelling