Exploring the bioactive landscape of the gut microbiota to identify metabolites underpinning human health

Abstract

The healthy human gut is colonised by a diverse microbial community (gut microbiota) that provides a variety of ecological and metabolic functions relevant to host health and well-being. Our early understanding and appreciation of the functional capacity of the microbiota was primarily informed by culture-dependent analyses. However, it is now known that the vast majority of gut microbes are resistant to cultivation and remain unrepresented by cultured isolates. Consequently, much of our current awareness of the true biological potential inherent to these communities has been provided by culture-independent (meta)genomic approaches which have revealed that the genetic potential of the gut microbiota is as much as 150 times greater than that of the human genome itself. Despite these advances it is now increasingly accepted that efforts to dissect the functionalities encoded in the human microbiome have not kept pace with DNA sequencing based technologies. For instance, the microbiome encodes a plethora of bioactive peptides and metabolites that affect host health, however, the function(s), mechanism(s) of action and the genetic and regulatory networks underpinning these bioactives remain largely cryptic. Here, we explore the NF-?B suppressive bioactive landscape of the gut microbiota-in particular, we provide an overview of our current understanding of the gut microbiota and propose the integration of new culture-dependent approaches with improved screening, metabolomic and genetic strategies offers new opportunities to identify novel bioactives, and elucidate the relationship between the gut microbiota associated metabolome and host health.