Microbial Species Abundance Distributions Guide Human Population Size Estimation from Sewage Metagenomes

Ling, Fangqiong; Chen, Likai; Zhang, Lin; Yu, Xiaoqian; Duvallet, Claire; Isazadeh, Siavash; Dai, Chengzhen; Park, Shinkyu; Frois-Moniz, Katya; Duarte, Fabio; Ratti, Carlo; Alm, Eric J.

The metagenome embedded in urban sewage is an attractive new data source to understand urban ecology and assess human health status at scales beyond a single host. However, using census-based population size instead of real-time population estimates can mislead the interpretation of data acquired from sewage, hindering assessment of representativeness’ inference of prevalence’ or comparisons of taxa across sites. Here’ we develop a new method to estimate human population size in light of recent developments in species-abundance distributions of microbial ecosystems. Using a population-scale human gut microbiome sample of over 1,100 people, we found that taxon-abundance distributions of gut-associated multi-person microbiomes exhibited generalizable relationships in response to human population size. We present a new non-parametric model, MicrobiomeCensus, for estimating human population size from sewage samples. MicrobiomeCensus harnesses the inter-individual variability in human gut microbiomes and performs maximum likelihood estimation based on simultaneous deviation of multiple taxa’s relative abundances from their population means. MicrobiomeCensus outperformed generic algorithms in data-driven simulation benchmarks and detected population size differences in field data. This research provides a mathematical framework for inferring population sizes in real time from sewage samples, paving the way for more accurate ecological and public health studies utilizing the sewage metagenome.