Moving pictures of the human microbiome

Abstract

Background: Understanding the normal temporal variation in the human microbiome is critical to developing treatments for putative microbiome-related afflictions such as obesity, Crohn’s disease, inflammatory bowel disease and malnutrition. Sequencing and computational technologies, however, have been a limiting factor in performing dense time series analysis of the human microbiome. Here, we present the largest human microbiota time series analysis to date, covering two individuals at four body sites over 396 timepoints.

Results: We find that despite stable differences between body sites and individuals, there is pronounced variability in an individual’s microbiota across months, weeks and even days. Additionally, only a small fraction of the total taxa found within a single body site appear to be present across all time points, suggesting that no core temporal microbiome exists at high abundance (although some microbes may be present but drop below the detection threshold). Many more taxa appear to be persistent but non-permanent community members.

Conclusions: DNA sequencing and computational advances described here provide the ability to go beyond infrequent snapshots of our human-associated microbial ecology to high-resolution assessments of temporal variations over protracted periods, within and between body habitats and individuals. This capacity will allow us to define normal variation and pathologic states, and assess responses to therapeutic interventions.

Figure 1

Principal coordinates analysis of unweighted UniFrac distances between samples. (a) Costello et al. [6] samples. (b) M3, F4 time series samples. (c) M3, F4 time series, PC1 versus time (days). Panels (a,b) and (c) show two independent principal coordinates analyses. To compare the Costello et al. 454 data (a) with the time series Illumina data (b), these data were generated in a single principal coordinates analysis of UniFrac distances at 500 sequences per sample. Panel (c) does not contain the 454 data, so makes use of the increased sampling depth possible on Illumina (evenly sampled to 5,000 sequences per sample for UniFrac calculations).

Figure 2

Temporal core microbiome. Fraction of species-level operational taxonomic units (OTUs) composing the core microbiota by number of samples in which an OTU must be present to be considered part of the core.

Figure 3

Community membership. Community membership summary for all OTUs in (a) M3 gut, (b) F4 gut, (c) M3 tongue, (d) F4 tongue, (e) M3 left palm, (f) F4 left palm, (g) M3 right palm, and (h) F4 right palm. Points are OTUs colored by their median relative abundance computed over all samples where they occur, and pie charts summarize the class-level taxa observed as persistent and transient OTUs.