Genomic Analysis of Intestinal Microbiota
Gut Microbiome in Human Health and Disease
The American Gastroenterological Association has developed the AGA Center for Gut Microbiome Research and Education to continue to advance research on the gut microbiome in human health and disease.
The human gut contains very large numbers of microbial species (somewhere between 500-1000) with some microorganisms reaching numbers as high as 1012 microbes per gram of feces. This makes the gut essentially a microbial organ. One of the major problems in the study of the gut microflora is that many of these microorganisms cannot be cultured. Thus, traditional microbiological culturing procedures, like those used in hospitals to identify disease-causing microorganisms, cannot be used to evaluate the gut microbiota. Fortunately, recent advances in gene sequencing technology allow for the complete sequencing, in a cost effective manner, of all DNA extracted from microbes in the gut. This new approach, termed metagenomics, allows for the taxonomic identification of the majority of gut microbes, referred to as gut microbiota, in the absence of culturing. These organisms together constitute the gut microbiome. This technology has revolutionized our understanding of what microbes are present in the gut as well as their ecology. Moreover, metagenomic approaches allow us to determine what microbes are present in the GI tract before and after intestinal microbiota transplantation. They also allow us to monitor the engraftment of microbiota and ultimately the cure of Clostridium difficile infection (CDI). This same technology can be used to follow the transplantation of gut microbes for other conditions and changes in the ecology of microbes living in/on other body sites.
While gene sequencing approaches have been effective in detailing what microbes are present in the human GI tract following IMT – essentially who is there, it does not tell us what these microbes are doing. This is called microbial functionality. To determine what functions microbes are carrying out, we can use technologies that can determine the types and amounts of the many small molecules present in the GI tract. This is often referred to as metabolomics. These small molecules are produced by gut microbes (via their diverse metabolism) as we digest food. In addition, chemical molecules are produced by microbes as they transform compounds produced by human metabolism. For example, metabolomics approaches have shown that gut microbes are intimately involved in the production of short chain fatty acids (acetate and butyrate) that are used by humans as energy sources and the conversion of bile produced by our liver and stored in the gallbladder. These bile compounds are involved in controlling C. difficile infection in humans, and the bacteria responsible for their conversion are restored following IMT.