Genomic “tweezer” ushers in new era of precision in microbiome research

In a landmark study published in the journal Natural methods, researchers at the Icahn School of Medicine at Mount Sinai unveiled mEnrich-seq, an innovative method designed to dramatically improve the specificity and efficiency of research into microbiomes, the complex communities of microorganisms that inhabit the body human. The article is titled “mEnrich-seq: methylation-guided enrichment sequencing of bacterial taxa of interest from the microbiome.”

Unlocking the microbial world with mEnrich-seq

Microbiomes play a crucial role in human health. An imbalance or decrease in the variety of microbes in our body 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 each type present. For example, when studying infectious diseases, researchers may only look at a few harmful gut bacteria, but these are mixed with many other bacteria.

“Imagine that you are a scientist who has to study a particular type of bacteria in a complex environment. It’s like trying to find a needle in a big haystack,” said Gang Fang, Ph.D., professor of genetics. and genomic sciences and the lead author of the study. “mEnrich-seq essentially gives researchers ‘smart tweezers’ to retrieve the needle of interest.

Once extracted by the “smart tweezers,” researchers can assemble the genome(s) of the targeted bacteria, thereby facilitating the study of various biomedical questions concerning them.

This new strategy fills a critical technology gap, because previously researchers had to isolate specific bacterial strains from a given sample using culture media that selectively cultivate the specific bacteria, a time-consuming process that works for some bacteria, but not for others. ‘others. mEnrich-seq, on the other hand, can directly recover the genome(s) of the bacteria of interest from the culture-free microbiome sample.

mEnrich-seq effectively distinguishes bacteria of interest from the broad context by exploiting the “secret codes” written on bacterial DNA that bacteria naturally use to differentiate from each other as part of their native immune system.

Transforming research and healthcare

The advent of mEnrich-seq opens new horizons in various fields:

• Cost-effectiveness: It offers a more cost-effective approach to microbiome research, particularly beneficial in large-scale studies where resources may be limited.
• Wide applicability: The method can focus on a wide range of bacteria, making it a versatile tool for research and clinical applications.
• Medical breakthroughs: By enabling more targeted research, mEnrich-seq could accelerate the development of new diagnostic tools and treatments.

“One of the most exciting aspects of mEnrich-seq is its ability to uncover previously missed details, such as antibiotic resistance genes that traditional sequencing methods could not detect due to a lack of sensitivity,” added Dr. Fang. “This could be a significant step forward in combating the global problem of antibiotic resistance.”

Indeed, as demonstrated in one of the three applications in this study, the authors used mEnrich-seq to directly reconstruct the pathogenic genomes of E. coli from urine samples of patients with urinary tract infections, which allowed a comprehensive analysis of 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 other diseases, as well as a response to cancer immunotherapy.

This bacteria is difficult to culture, so mEnrich-seq can be a useful tool to reconstruct its genome in a culture-independent, sensitive and cost-effective manner, which can facilitate larger-scale association studies with different diseases human.

The future of mEnrich-seq

Looking ahead, the team has ambitious plans for mEnrich-seq. They aim to refine the method to further improve its effectiveness and broaden its range of applications. Collaborations with clinicians and health professionals are also underway to validate the usefulness of the method 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.