The first decade of research emanating from the establishment of the “human microbiome” as a distinct field of study has been enabled in large part by the rapid technological advances in DNA sequencing methods and computational analyses.  Our understanding of the impacts of host-microbiota interactions on acute and chronic non-communicable diseases was particularly advanced by the application of 16S rRNA gene profiling and DNA/RNA sequencing approaches to small animal models and human studies.  Together, these advanced our understanding and awareness of the microbes that exist in these communities and revealed dramatic structural-function alterations that are co-incident with the onset of disease.  Critically, they revealed that coverage of the 9.8 million non-redundant genes that comprise the gut microbiome has been largely saturated.  However, many of these studies have been largely observational and while it is now widely accepted that the gut microbiota sets the tenor of intestinal mucosal immunity and the predisposition to inflammation, they have not yet translated into strategies to maintain health or ameliorate disease risk.

There is now a rapidly growing interest in harnessing the immunomodulatory capacity of the microbiota however it is indisputable that the development of new culturing and genetic methods for fastidious gut bacteria have not kept pace with -omic methods.  To address this gap in knowledge we developed new approaches to selectively isolate genetically tractable human colonic Firmicutes, including mucosa associated taxa, as these are functionally diverse but significantly underrepresented in existing bacterial culture collections.  Using a rational screening strategy, we have now identified numerous immunomodulatory bacteria and determined that these functional capacities may be more widespread than previously appreciated.  Collectively, this offers new opportunities to link genes with function in a time and cost-effective manner as we enter the second decade of human microbiome research.