Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, here we characterize bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy children and adults from the Amazonas of Venezuela, rural Malawi and US metropolitan areas and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial assemblages and functional gene repertoires were noted between US residents and those in the other two countries. These distinctive features are evident in early infancy as well as adulthood. Our findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations and the impact of westernization.

This paper is motivated by the recent interest in the analysis of high-dimensional microbiome data. A key feature of these data is the presence of "structural zeros" which are microbes missing from an observation vector due to an underlying biological process and not due to error in measurement. Typical notions of missingness are unable to model these structural zeros. We define a general framework which allows for structural zeros in the model and propose methods of estimating sparse high-dimensional covariance and precision matrices under this setup. We establish error bounds in the spectral and Frobenius norms for the proposed estimators and empirically verify them with a simulation study. The proposed methodology is illustrated by applying it to the global gut microbiome data of Yatsunenko and others (2012. Human gut microbiome viewed across age and geography. Nature 486, 222-227). Using our methodology we classify subjects according to the geographical location on the basis of their gut microbiome.