biostudies-literatureWu-Woods NJUnited States Department of Defense | United States Army | U.S. Army Research, Development and Engineering Command | Army Research OfficeUChicago | Digestive Diseases Research Core Center, University of ChicagoKenneth Rainin FoundationNational Science Foundation fellowshipNational Institutes of Health Biotechnology Leadership Pre-doctoral Training Program (BLP) fellowship from Caltech’s Donna and Benjamin M. Rosen Bioengineering CenterNIDDK NIH HHSU.S. Department of Health & Human Services | National Institutes of HealthNIGMS NIH HHS1672-1682https://www.ebi.ac.uk/biostudies/studies/S-EPMC10885704biostudies-literatureUnknown20(11)Host-microbe interactions have been linked to health and disease states through the use of microbial taxonomic profiling, mostly via 16S ribosomal RNA gene sequencing. However, many mechanistic insights remain elusive, in part because studying the genomes of microbes associated with mammalian tissue is difficult due to the high ratio of host to microbial DNA in such samples. Here we describe a microbial-enrichment method (MEM), which we demonstrate on a wide range of sample types, including saliva, stool, intestinal scrapings, and intestinal mucosal biopsies. MEM enabled high-throughput characterization of microbial metagenomes from human intestinal biopsies by reducing host DNA more than 1,000-fold with minimal microbial community changes (roughly 90% of taxa had no significant differenceNature methodsMicrobial-enrichment method enables high-throughput metagenomic characterization from host-rich samples.PMC10885704W911NF-17-1-0402DK067180RC2 DK122394T32 GM112592T32 GM1503755F30DK121470P30 DK042086P30 DK42086RC2 DK133947F30 DK121470R01 DK067180Barlow JTShaw DGJabri BTrigodet FIsmagilov RFRomano AEEren AMWu-Woods NJfalseMicrobial-enrichment method enables high-throughput metagenomic characterization from host-rich samples.Host-microbe interactions have been linked to health and disease states through the use of microbial taxonomic profiling, mostly via 16S ribosomal RNA gene sequencing. However, many mechanistic insights remain elusive, in part because studying the genomes of microbes associated with mammalian tissue is difficult due to the high ratio of host to microbial DNA in such samples. Here we describe a microbial-enrichment method (MEM), which we demonstrate on a wide range of sample types, including saliva, stool, intestinal scrapings, and intestinal mucosal biopsies. MEM enabled high-throughput characterization of microbial metagenomes from human intestinal biopsies by reducing host DNA more than 1,000-fold with minimal microbial community changes (roughly 90% of taxa had no significant difference2023-01-01T00:00:00Z2023 Nov2026-06-02T06:17:33.84Z2025-04-04T09:58:51.33ZS-EPMC108857043782815210.1038/s41592-023-02025-4