Dynamics and associations of microbial community types across the human body

Abstract

A primary goal of the Human Microbiome Project (HMP) was to provide a reference collection of 16S ribosomal RNA gene sequences collected from sites across the human body that would allow microbiologists to better associate changes in the microbiome with changes in health. The HMP Consortium has reported the structure and function of the human microbiome in 300 healthy adults at 18 body sites from a single time point. Using additional data collected over the course of 12-18 months, we used Dirichlet multinomial mixture models to partition the data into community types for each body site and made three important observations. First, there were strong associations between whether individuals had been breastfed as an infant, their gender, and their level of education with their community types at several body sites. Second, although the specific taxonomic compositions of the oral and gut microbiomes were different, the community types observed at these sites were predictive of each other. Finally, over the course of the sampling period, the community types from sites within the oral cavity were the least stable, whereas those in the vagina and gut were the most stable. Our results demonstrate that even with the considerable intra- and interpersonal variation in the human microbiome, this variation can be partitioned into community types that are predictive of each other and are probably the result of life-history characteristics. Understanding the diversity of community types and the mechanisms that result in an individual having a particular type or changing types, will allow us to use their community types to assess disease risk and to personalize therapies.

Extended Data Figure 1. Comparison of community type assignments for non-metric dimensional scaling (NMDS) ordination of Jensen-Shannon divergence values between stool samples using DMM (A) and PAM-based clustering (B)

The stress computed for this ordination was 0.19 and the R² between the input distance matrix and the distance matrix calculated between the points in the ordination was 0.90.

Extended Data Figure 2

Percentage of female and male tongue communities that affiliated with each of the tongue (A; N=288 unique individuals; median P=2×10⁻³), right retroauricular crease (B; N=268 unique individuals; median P=9×10⁻⁵), and right antecubital fossa community types (C; N=136 unique individuals; median P=3×10⁻⁵).

Extended Data Figure 3

Percentage of women with and without a college degree whose vaginal communities affiliated with the vaginal introitus (A; N=74 unique individuals; median P=2×10⁻³), mid-vagina (B; N=64 unique individuals; median P=8×10⁻⁴), and posterior fornix (C; N=61 unique individuals; median P=4×10⁻⁴) community types.

Figure 1. Analysis of stool samples reveals four community types

(A) Fitting the genera-level relative abundance data from 597 stool samples to Dirichlet multinomial mixture models provided support for four types when using the Laplace approximation to the negative log model evidence. (B) The relative abundance of the most abundant genera in the samples assigned to each of the types (The boxes represent the interquartile range and the error bars represent the 95% confidence interval; N_{Community Type A}=221; N_{Community Type B}=15; N_{Community Type C}=80; N_{Community Type D}=281). There were significant associations between stool community types (N=287 unique individuals) with whether the subject was breastfed as an infant (C; median P=1×10⁻⁴) and their gender (D; median P=4×10⁻⁴).

Figure 2. Community-type associations are strongest within a body region, but also exist between stool and the oral cavity

Heatmap colors represent the magnitude of the median P-value for the comparison of community type membership using Fisher’s Exact Test. Median P-values are found in the Source Data.

Figure 3. Dynamics of community types at various body sites suggests that community type stability is correlated with the diversity of the community type

(A) The community types at each body site differ in the fraction of samples that change their community type membership between visits. (Size of circles represents percentage of samples that affiliated with each community type and the vertical line represents the weighted average). (B) Rate of change between stool community types (N_{Community Type A}=221; N_{Community Type B}=15; N_{Community Type C}=80; N_{Community Type D}=281). The numbers on directed edges indicate the percentage of samples that changed community types.