Human Gut Microbiome: Function Matters

Functional omics are becoming more accessible, and increasing numbers of studies have employed them, demonstrating their potential in identifying functional traits of the microbiome related to health and disease. Functional omes display greater variability and sensitivity to perturbation, also in cases of where changes in taxonomic composition are minimal, and they can resolve gut-compartment-specific information. Methods for resolving functional differences in meta-omic datasets to the taxa contributing them have been developed and are necessary to understand the impact of microbial functions on human physiology. The human gut microbiome represents a complex ecosystem contributing essential functions to its host. Recent large-scale metagenomic studies have provided insights into its structure and functional potential. However, the functional repertoire which is actually contributed to human physiology remains largely unexplored. Here, by leveraging recent omics datasets, we challenge current assumptions regarding key attributes of the functional gut microbiome, in particular with respect to its variability. We further argue that the closing of existing gaps in functional knowledge should be addressed by a most-wanted gene list, the development and application of molecular and cellular high-throughput measurements, the development and sensible use of experimental models, as well as the direct study of observable molecular effects in the human host. The human gut microbiome represents a complex ecosystem contributing essential functions to its host. Recent large-scale metagenomic studies have provided insights into its structure and functional potential. However, the functional repertoire which is actually contributed to human physiology remains largely unexplored. Here, by leveraging recent omics datasets, we challenge current assumptions regarding key attributes of the functional gut microbiome, in particular with respect to its variability. We further argue that the closing of existing gaps in functional knowledge should be addressed by a most-wanted gene list, the development and application of molecular and cellular high-throughput measurements, the development and sensible use of experimental models, as well as the direct study of observable molecular effects in the human host. systems that can be employed as a model for the human microbiome and which are amenable to manipulation; they range from mixed-species and automated culturing, cell-culture-based coculture systems, and, as all animals carry a microbiome, animal models, including germ-free or gnotobiotic animals, including those with a ‘humanized’ microbiome. are commonly applied to describe the functions encoded or carried out by the microbiome (the functional complement), usually by grouping genes into metabolism-centered frameworks, such as the orthology put forth by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the MetaCyc database, or functionally annotated orthologous groups based on sequence similarity, such as eggNOG. is a measure of the number (richness) and distribution of different functions within the community. It is related to gene richness but also to phylogenetic diversity, as microbial communities with phylogenetically diverse members often have a wider functional potential. Phylogenetic diversity and functional diversity have been observed as traits of human gut microbiota which are relatively stable over time. the ability of the microbial community or its members to adapt to perturbations by changing gene expression; it can stabilize the taxonomic community structure as well as ecosystem functions. is a measure of the number of different populations within a community that are able to perform the same functions. Functional redundancy can increase functional resilience, in case perturbations affect the taxonomic community structure; this allows for a return to community function, and therefore can increase stability. seek to manipulate the human microbiome in situ, by means of nutrition, probiotics, antibiotics, or faecal transplants. refers to the analysis of genomic DNA for mixtures of (often unknown) species. Its purpose can be to assess the taxonomic composition of a mixed microbial community or to elucidate the functional potential of its members. (also referred to as metabonomics, mainly in the context of research on single organisms) technologies that measure intra- and/or extracellular metabolites in and around microbial communities. aims to characterize microbial activity by applying the analysis of proteomes to mixed-species assemblages. is the term applied to the analysis of RNA of communities, usually with the aim of inferring activity. a group of methodologies that aim at the characterization of the total pool of a class of biomolecules, including metagenomics, (meta)metabolomics, metaproteomics, and metatranscriptomics. to quantify the taxa and functions detected in a sample form part of most meta-omic studies of the human microbiome. Increasingly, taxonomic resolution of functions of interest within the microbiome is also achieved.