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Microbiome study finds bacteria in human gut rarely update their CRISPR defense systems

Dec 23, 2024

These bacteria can be vulnerable to infection from viruses called bacteriophages. One of bacterial cells most well-known defenses against these viruses is the CRISPR system which evolved in bacteria to help them recognize and chop up viral DNA.

A study from MIT biological engineers has yielded new insight into how bacteria in the gut microbiome adapt their CRISPR defenses as they encounter new threats. The researchers found that while bacteria grown in the lab can incorporate new viral recognition sequences as quickly as once a day bacteria living in human gut add new sequences at a much slower rate on average one every three years.

The findings suggest that the environment within the digestive tract offers many fewer opportunities for bacteria and bacteriophages to interact than in the lab so bacteria don't need to update their CRISPR defenses very often. It also raises the question of whether bacteria have more important defense systems than CRISPR.

This finding is significant because we use microbiome-based therapies like fecal microbiota transplant to help treat some diseases but efficacy is inconsistent because new microbes do not always survive in patients. Learning about microbial defenses against viruses helps us to understand what makes a strong healthy microbial community says An-Ni Zhang a former MIT postdoc who is now an assistant professor at Nanyang Technological University.

Zhang is the lead author of the study which appears in the journal Cell Genomics. Eric Alm director of MIT's Center for Microbiome Informatics and Therapeutics a professor of biological engineering and of civil and environmental engineering at MIT and a member of the Broad Institute of MIT and Harvard is the paper's senior author.

In bacteria CRISPR serves as a memory immune response. When bacteria encounter viral DNA they can incorporate part of the sequence into their own DNA. Then if the virus is encountered again that sequence produces a guide RNA that directs an enzyme called Cas9 to snip the viral DNA preventing infection.

These virus-specific sequences are called spacers and a single bacterial cell may carry more than 200 spacers. These sequences can be passed onto offspring and they can also be shared with other bacterial cells through a process called horizontal gene transfer

We were interested in how fast this CRISPR system changes its spacers specifically in the gut microbiome to better understand the bacteria-virus interactions inside our body Zhang says. We wanted to identify the key parameters that impact the timescale of this immunity update.

To do that the researchers looked at how CRISPR sequences changed over time in two different datasets obtained by sequencing microbes from the human digestive tract. One of these datasets contained 6,275 genomic sequences representing 52 bacterial species and the other contained 388 longitudinal metagenomes that is sequences from many

Source:https://phys.org/news/2024-12-microbiome-bacteria-human-gut-rarely.html


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