Microbial-enrichment method enables high-throughput metagenomic characterization from host-rich samples

Area of Science:

• Microbiology
• Genomics
• Host-Microbe Interactions

Background:

• Host-microbe interactions are crucial for health and disease, often studied via 16S rRNA sequencing.
• Studying microbial genomes in host tissues is challenging due to high host DNA ratios.
• Mechanistic insights into host-microbe interactions are limited by current methodologies.

Purpose of the Study:

• To introduce and validate a microbial enrichment method (MEM) for analyzing host-associated microbial communities.
• To overcome the challenge of high host DNA contamination in tissue samples.
• To enable high-throughput characterization of microbial metagenomes from host tissues.

Main Methods:

• Development and application of a microbial enrichment method (MEM).
• Demonstration of MEM on diverse sample types including saliva, stool, and intestinal biopsies.
• Shotgun sequencing of MEM-treated samples for metagenomic analysis.

Main Results:

• MEM reduced host DNA by over 1,000-fold in human intestinal biopsies with minimal impact on microbial communities.
• Enabled characterization of both high- and low-abundance microbial taxa, pathways, and genes.
• Facilitated the construction of metagenome-assembled genomes from bacteria and archaea at 1% abundance.

Conclusions:

• MEM significantly enhances the ability to study host-tissue-associated microbial communities.
• The method allows for deeper characterization of microbial populations, including distinct subpopulations.
• MEM provides a pathway for acquiring deeper insights into host-microbe interactions.