Human gut metagenomics: Success and limits of the activity-based approaches

Abstract

The symbiotic relationship between the host and its gut microbiota has evolved to benefit both parties, especially by maintaining the host health and providing nutrients to the microbiota. Until recently, the study of this complex relationship was limited to culture-based studies. For this purpose, functional metagenomics has proved to be a powerful technique for exploring the diversity of the microbiota, discovering new functions and signaling pathways and extending our knowledge in the cross talk between the host and its gut microbiota. By assigning functions to proteins without any a priori knowledge of their sequences, the activity-based metagenomic approach allows to rationalize the sequencing efforts, to boost enzyme discovery, and to obtain knowledge on their mode of action, from the molecular to the ecosystem scales. This review offers an overview of the recent results obtained by activity-based metagenomic approach on the exploration of the human gut microbiota and gives insights on future developments and promising discoveries in the field.