LARGE INTESTINE (B CASH, SECTION EDITOR) The Colonic Microbiota and Colonic Disease Fergus Shanahan Published online: 1 September 2012 # Springer Science+Business Media, LLC 2012 Abstract The colonic ecosystem differs from that in the proximal gut in several important respects. The colonic microbiota represents the largest population of microbes colonizing humans from birth. Constraints on bacterial numbers, composition, and interaction with the host involve not only the innate and acquired immune system, but also the colonic mucin structure. While the microbiota provides beneficial protective, trophic, nutritional, and metabolic sig- nals for the host, it may become a risk factor for disease depending on context and host susceptibility. Technological advances including DNA-based high-throughput composi- tional analysis have linked changes in the indigenous micro- biota with several human diseases. In some instances, these findings have the potential to serve as new biomarkers of risk of disease. In this overview, recent advances are focused upon in relation to irritable bowel syndrome, inflammatory bowel disease, and colon cancer. The possibility that the therapeutic solution to some of these disorders may reside within the microbiota will also be addressed. Keywords Inflammatory bowel disease . Irritable bowel syndrome . Colon cancer . Clostridium difficile Introduction The human colonic microbiota may be regarded at once as a friend, bystander, and sometime villain. Essential for opti- mal development and maintenance of gastrointestinal ho- meostasis throughout life, components of the microbiota occasionally become risk factors for disease in susceptible hosts. The microbiota provides protective, metabolic, and nutritional signals in health, but when host–microbe mutu- alism breaks down, the host is at risk of developing a diversity of gastrointestinal and extraintestinal inflammatory and metabolic disorders. Most of the resident microbes in humans reside in the colon, and the fecal microbiota is most commonly studied as a surrogate for the colonic microbiota. Testimony to the status of the microbiota as one of the hottest areas of biology is given by the exponential rate of publications on the topic over the past decade [1, 2]. While the scope of research on the microbiota is widening and includes rapidly emerging information on the gut viriome, this overview will be limited to a perspective on the emerg- ing role of colonic bacteria as an environmental risk factor for colonic diseases, such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), colon cancer, and Clos- tridium difficile-associated disease, while acknowledging that these conditions are not exclusive to the colon. Recent advances are emphasized; readers will find over 500 reviews on different aspects of host–microbe interactions and are referred elsewhere for earlier work, comprehensive reviews, and studies of the role of the microbiota in extra-colonic disorders, including obesity, metabolic syndrome, diabetes, and cardiovascular disease [2–5]. The Colonic Microenvironment The colonic eco-niche differs in some important respects from that in the small bowel and proximal alimentary tract. First, the colonic microbiota exceeds that of the small bowel by several log-fold; second, exposure time to the microbiota in the colon exceeds that of the proximal gut, where contin- ual peristalsis moves luminal contents relatively quickly. Host–microbe interactions throughout the gut are bidirec- tional, the microbiota influencing the maturation and F. Shanahan (*) Department of Medicine and Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Dublin, Ireland e-mail: F.Shanahan@ucc.ie Curr Gastroenterol Rep (2012) 14:446–452 DOI 10.1007/s11894-012-0281-5