Project

Population dynamics of human small intestinal microbiota

The aim of this project is to elucidate the population dynamics of the human small intestinal microbiota.

This project is part of the research project “Complex Fermentations” of the Top Institute Food

and Nutrition (TIFN).

Introduction

The human gastrointestinal (GI) tract is inhabited by a diverse microbiota, which predominately consists of (anaerobic) bacteria (Zoetendal et al., 2006). The human host andthe intestinal bacteria coexist in a mutualistic relationship (Backhed et al., 2005). A stable habitat, rich in energy sources deriving from the diet, is provided by the host epithelium of the GI tract, while the endogenous bacteria provide metabolic, protective, and immunomodulatory functions to the benefit of the host.

Development of culture-independent strategies in the last decade have led to a considerable increase in understanding the GI tract ecology (Zoetendal et al., 2008). Previous studiesmostly focused on characterizing the bacterial population of the large intestine, since sampling from the distal colon is relatively easy. In contrast, the small intestine is poorly accessible and thus the microbiota of this region of the GI tract has remained relatively unexplored. However, the small intestine is a major site for food digestion, and absorption, and is prominently involved in immunological perception. Moreover, the small intestine is the first region where the intestinal microbiota comes in contact with food materials. These findings justify further research of the small intestinal microbiota.

Research Approach

16S rRNA gene clone libraries have been constructed using effluent samples of healthy ileostomists. Sequences of cloned amplicons are used for the design of a dedicatedphylogenetic diagnostic microarray, which will be applied to determine the small intestinal microbial diversity as a function of time and dietary habits and in different individuals. In addition, small intestine specific bacterial groups will be targeted by 16S rRNA probes for Fluorescent in situ Hybridization (FISH) to quantify bacterial populations in small intestinal samples. Classical anaerobic cultivation techniques and novel microdish technology will be employed to isolate and culture bacteria from samples of the small intestine. Based on the acquired data a microbiota dynamics model for the human small intestine will be constructed, which will be employed to predict and validate observations made during dietary intervention studies.

References:

Backhed, F., Ley, R.E., Sonnenburg, J.L., Peterson, D.A., and Gordon, J.I. (2005) Hostbacterial mutualism in the human intestine. Science 307: 1915-1920.

Zoetendal, E.G., Vaughan, E.E., and de Vos, W.M. (2006) A microbial world within us. Mol Microbiol 59: 1639-1650.

Zoetendal, E.G., Rajilic-Stojanovic, M., and de Vos, W.M. (2008) High-throughput diversity and functionality analysis of the gastrointestinal tract microbiota. Gut 57: 1605-1615.