Summary Many United States immigrant populations develop metabolic diseases post-immigration, but the causes are not well understood. Although the microbiome plays a role in metabolic disease, there have been no studies measuring the effects of U.S. immigration on the gut microbiome. We collected stool, dietary recalls, and anthropometrics from 514 Hmong and Karen individuals living in Thailand and the U.S., including first- and second-generation immigrants and 19 Karen individuals sampled before and after immigration, as well as from 36 U.S.-born European American individuals. Using 16S and deep shotgun metagenomic DNA sequencing, we found that migration from a non-Western country to the U.S. is associated with immediate loss of gut microbiome diversity and function, in which U.S.-associated strains and functions displace native strains and functions. These effects increase with duration of U.S. residence, and are compounded by obesity and across generations.

Highlights d Daily microbiome variation is related to food choices, but not to conventional nutrients d Daily microbiome variation depends on at least two days of dietary history d Similar foods have different effects on different people's microbiomes

A common refrain in recent microbiome-related academic meetings is that the field needs to move away from broad taxonomic surveys using 16S sequencing and toward more powerful longitudinal studies using shotgun sequencing. However, performing deep shotgun sequencing in large longitudinal studies remains prohibitively expensive for all but the most well-funded research labs and consortia, which leads many researchers to choose 16S sequencing for large studies, followed by deep shotgun sequencing on a subset of targeted samples. Here, we show that shallow- or moderate-depth shotgun sequencing may be used by researchers to obtain species-level taxonomic and functional data at approximately the same cost as amplicon sequencing. While shallow shotgun sequencing is not intended to replace deep shotgun sequencing for strain-level characterization, we recommend that microbiome scientists consider using shallow shotgun sequencing instead of 16S sequencing for large-scale human microbiome studies.