Determining Microbial Products and Identifying Molecular Targets in the Human Microbiome

Abstract

Human-associated microbes are the source of many bioactive microbial products (proteins and metabolites) that play key functions both in human host pathways and in microbe-microbe interactions. Culture-independent studies now provide an accelerated means of exploring novel bioactives in the human microbiome; however, intriguingly, a substantial fraction of the microbial metagenome cannot be mapped to annotated genes or isolate genomes and is thus of unknown function. Meta'omic approaches, including metagenomic sequencing, metatranscriptomics, metabolomics, and integration of multiple assay types, represent an opportunity to efficiently explore this large pool of potential therapeutics. In combination with appropriate follow-up validation, high-throughput culture-independent assays can be combined with computational approaches to identify and characterize novel and biologically interesting microbial products. Here, we briefly review the state of microbial product identification and characterization and discuss possible next steps to catalog and leverage the large uncharted fraction of the microbial metagenome.

Integrated multi-omics of the human gut microbiome in a case study of familial type 1 diabetes

“…Nonetheless, the apparent higher complexity and variability exhibited by the functional omic levels necessitates an integrated analysis of the individual omic data sets 18,50 to facilitate a reliable link between specific microbial genes and their genomic context. Linking genes of interest to genomic context has been attempted in other studies of T1DM by correlating abundances of functional traits and organisms 32 .…”

Emerging Technologies for Gut Microbiome Research

“…In order to achieve a meaningful synergy of diverse information sources such as taxonomic [106] and functional [107, 108] profiling, the results of multiple bioinformatic analyses and meta-analyses need to be combined in a principled manner. Preliminary investigations in this direction have produced promising results [45, 109, 110], but significant development opportunities remain.…”

Anaerobic 4-hydroxyproline utilization: Discovery of a new glycyl radical enzyme in the human gut microbiome uncovers a widespread microbial metabolic activity

“…2 While much progress has been made in characterizing community compositions, we know surprisingly little about the biochemical functions of the gut microbiota and the mechanisms by which microbes influence host biology. 3 In order to understand the metabolic potential of the gut microbiota and inform mechanistic research, it is imperative that we link the genes present in this habitat to functions. However, the biological roles of most microbial genes remain unidentified, indicating a great need to investigate this uncharacterized genetic information.…”

“…However, the biological roles of most microbial genes remain unidentified, indicating a great need to investigate this uncharacterized genetic information. 3 , 4 …”