Quantifying the metabolic activities of human-associated microbial communities across multiple ecological scales

Abstract

Humans are home to complex microbial communities, whose aggregate genomes and their encoded metabolic activities are referred to as the human microbiome. Recently, researchers have begun to appreciate that different human body habitats and the activities of their resident microorganisms can be better understood in ecological terms, as a range of spatial scales encompassing single cells, guilds of microorganisms responsive to a similar substrate, microbial communities, body habitats, and host populations. However, the bulk of the work to date has focused on studies of culturable microorganisms in isolation or on DNA sequencing-based surveys of microbial diversity in small to moderately sized cohorts of individuals. Here, we discuss recent work that highlights the potential for assessing the human microbiome at a range of spatial scales, and for developing novel techniques that bridge multiple levels: for example, through the combination of single cell methods and metagenomic sequencing. These studies promise to not only provide a much-needed epidemiological and ecological context for mechanistic studies of culturable and genetically tractable microorganisms, but may also lead to the discovery of fundamental rules that govern the assembly and function of host-associated microbial communities.

Gut microbial functional maturation and succession during human early life

“…The strongest negative ratios were observed in Streptococcus , Veillonella , Enterococcus and Blautia whereas the positive ratios observed for Faecalibacterium, Flavonifractor and Oscillibater suggested high biological activity. Thus, our metaproteomics data revealed that the gut microbiota harbours a distinctive subset of biologically active microorganisms as consistently shown in other reports (McNulty et al ., ; Ferrer et al ., ; Maurice et al ., ; Maurice and Turnbaugh, ; Perez‐Cobas et al ., ). While we cannot exclude analytical biases in DNA and protein extraction methods, these discordances suggest that using bacterial taxa as input information to build predictive theoretical models of microbial activity and contribution to community functioning in human gut microbial ecosystems may be highly misleading.…”

Gut microbiota, metabolites and host immunity

“…Characterization and quantification of individual microbial cells can be achieved using flow cytometry with tandem mass spectrometry to measure metabolic activity 106 . This single-cell strategy enables the analysis of cell-to-cell functional variation and the discovery of novel regulatory mechanisms.…”

The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism

“…Recent advances in the culture-independent interrogation of microbial community structure 1, 2 and function 2–4 , including advances in sequencing technologies and the development of bioinformatic tools, have spawned a veritable “ microbiome renaissance”. Due to these advances, the microbiota is now often referred to as the “forgotten organ” due to our understanding and appreciation of its contributions to host physiology, metabolism, and disease 5 .…”