The Gut Microbiota as Target for Innovative Drug Development: Perspectives and a Case Study of Inflammatory Bowel Diseases

Abstract

For many centuries scientists have been intrigued by the function of the intestine in human health and have tried to explain the role of the intestinal tract in our body, with sometimes rather original interpretations of its function. Leonardo Da Vinci for instance, who described the anatomy of the human body in great detail, concluded that the digestive system is in fact a part of the respiratory system, supporting its functioning. Indeed, he stated the following, giving a quite original interpretation on the function of the intestines: "The compressed intestines with the condensed air which is generated in them, thrust the diaphragm upwards; the diaphragm compresses the lungs and expresses the air" (O'Malley & Saunders, 1982). So gasses produced in the intestine would help to breath... In general, until quite recently it was believed that the main function of the intestine would be to dispose waste materials and reabsorb water from the intestine. Since the work of Antonie Van Leeuwenhoek it is known that the intestine contains an extensive microbial community (Smit & Heniger, 1975). Nowadays, it’s clear that the intestine is much more than an organ for waste material and absorption of water, salts and drugs, and indeed has a very important impact on human health, for a major part related to the specific composition of the complex microbial community in the colon. This microbial community composition is governed by age, diet, environment and phylogeny (Ley et al., 2008; Zoetendal et al., 1998; Zoetendal et al., 2001) and contains all three domains of life: Bacteria, Archaea and Eukarya (fungi, yeasts and protozoa). The human colon harbors a highly complex microbial ecosystem of about 200 g living cells, at concentrations of 1011 microorganisms per gram gut content, in total numbers which outnumber the amount of somatic and germ cells in the human body with a factor 10. Together, all 6.5 billion humans on earth represent a gut reservoir of 1023-1024 microbial cells, which is just five orders of magnitude less than the world’s oceans (1029 cells) (Ley et al., 2006). Therefore, the human gut constitutes a substantial habitat in our biosphere and we can in fact consider the human body as a mix of human and bacterial cells. Despite such high numbers, the microbial diversity is however relatively limited. Although 55 and 13 divisions of respectively Bacteria and Archaea have been described, only 8 bacterial