Metagenomics is an emerging field focused on characterizing the structures, functions and dynamic operations of microbial communities sampled in their native habitats without the need for culture. Here, we present findings from a 16S rRNA gene sequence‐ and whole community DNA shotgun sequencing‐based analysis of the adult human gut microbiomes of lean and obese mono‐ and dizygotic twins. Our findings indicate that a core microbiome can be found at the gene level, despite large variation in community membership, and that variations from the core are associated with obesity. These findings have implications for ongoing Human Microbiome Project(s), and highlight important challenges to the field of metagenomics.