What is the role of the metabolic activity of the gut microbiota in inflammatory bowel disease? Probing for answers with stable isotopes.

The pathogenesis of inflammatory bowel disease remains obscure. However, there has been increasing interest in the role of the gut microbiota, focusing in particular on the "unculturable majority" of luminal and mucosal bacteria, which until recently have been difficult to study owing to the technical challenges of identification and elucidating function. Bacterial components and metabolites have been implicated in signalling to host immune systems and regulating inflammatory responses. Although the rapid expansion in techniques of molecular microbiology has increased our understanding of bacterial diversity, the tools to assess bacterial metabolic activity, and to link the 2, lag behind. Stable isotope probing is a powerful technique to link the metabolic activity and diversity of "unculturable" bacteria through isotopic labelling of biomarkers such as DNA and RNA. Progression of current stable isotope probing methodology with high-resolution oligonucleotide 16s rRNA probe technology and high precision liquid chromatographic isotope ratio mass spectrometry may facilitate application in human microbial ecology. Progress towards stable isotope probing use in vivo, in concert with other advances in bacterial metabolome analysis, will lead to the development of a dynamic picture of the metabolic activity and diversity of intestinal bacteria in inflammatory bowel disease. Such insights will, over time, lead to fuller understanding of inflammatory bowel disease pathogenesis and the development of targeted therapies to reverse the "dysbiosis" that precedes disease relapse.