Genomic 'tweezer' ushers in a new era of precision in microbiome research

January 4, 2024 This article has been reviewed according to Science X's editorial process and policies . Editors have highlighted the following attributes while ensuring the content's credibility: fact checked peer reviewed publication trusted source proofread by The Mount Sinai Hospital In a landmark study published in the journal Nature Methods , researchers at the Icahn School of Medicine at Mount Sinai have unveiled mEnrich seq—an innovative method designed to substantially enhance the specificity and efficiency of research into microbiomes, the complex communities of microorganisms that inhabit the human body.

The paper is titled "mEnrich seq: methylation guided enrichment sequencing of bacterial taxa of interest from microbiome." Microbiomes play a crucial role in human health. An imbalance or a decrease in the variety of microbes in our bodies can lead to an increased risk of several diseases.

However, in many microbiome applications, the focus is on studying specific types of bacteria in a sample, rather than looking at each type present. For example, when studying infectious diseases , researchers might only be interested in a few harmful gut bacteria, but they are mixed in with many other bacteria.

"Imagine you're a scientist who needs to study one particular type of bacteria in a complex environment. It's like trying to find a needle in a large haystack," said Gang Fang, Ph.D., Professor of Genetics and Genomic Sciences and the study's senior author. "mEnrich seq essentially gives researchers a 'smart tweezer' to pick up the needle they're interested in." Once pulled out by the "smart tweezer," researchers can assemble the genome(s) of the targeted bacteria, facilitating the study of diverse biomedical questions about them.

This new strategy addresses a critical technology gap, as previously researchers would need to isolate specific bacterial strains from a given sample using culture media that selectively grow the specific bacterium—a time consuming process that works for some bacteria, but not others. mEnrich seq, in contrast, can directly recover the genome(s) of bacteria of interest from the microbiome sample without culturing.

mEnrich seq effectively distinguishes bacteria of interest from the vast background by exploiting the "secret codes" written on bacterial DNA that bacteria use naturally to differentiate among each other as part of their native immune systems. The advent of mEnrich seq opens new horizons in various fields: "One of the most exciting aspects of mEnrich seq is its potential to uncover previously missed details, like antibiotic resistance genes that traditional sequencing methods couldn't detect due to a lack of sensitivity," Dr.

Fang added. "This could be a significant step forward in combating the global issue of antibiotic resistance." Indeed, as demonstrated as one of three applications in this study, the authors used mEnrich seq to directly reconstruct pathogenic E. coli genomes from urine samples from patients with urinary tract infections , which allowed the comprehensive analysis of the antibiotic resistance genes in each genome.

In another application, the authors used mEnrich seq to selectively construct the genomes of Akkermansia muciniphila, a bacterium that has been shown to have benefits in obesity and diabetes, among several other diseases, as well as a response to cancer immunotherapy. This bacterium is hard to culture, so mEnrich seq can be a useful tool to reconstruct its genome in a culture independent, sensitive, and cost effective way, which may facilitate larger scale association studies with different human diseases.

Looking ahead, the team has ambitious plans for mEnrich seq. They aim to refine the method to improve its efficiency further and to expand its range of applications. Collaborations with clinicians and health care professionals are also in the pipeline to validate the method's utility in real world settings.

"We envision mEnrich seq as a sensitive and versatile tool in the future of microbiome studies and clinical applications," said Dr. Fang. More information: mEnrich seq: methylation guided enrichment sequencing of bacterial taxa of interest from microbiome, Nature Methods (2024). DOI: 10.1038/s41592 023 02125 1 www.nature.com/articles/s41592 023 02125 1 Journal information: Nature Methods Provided by The Mount Sinai Hospital.