Gut bacteria update CRISPR defense only once every three years, study finds

A new study reveals that bacteria in our guts update their defenses against viruses far more slowly than expected. On average, these microbes modify their CRISPR-based immune system only once every three years. This finding challenges the assumption that gut bacteria are constantly adapting to viral threats and suggests they may rely on other, less obvious defense mechanisms.

Bacterial immune system

CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, acts like a bacterial immune system. It works by cutting up the DNA of invading viruses, preventing them from replicating. Because the human gut is teeming with viruses, scientists expected that gut bacteria would continuously update their CRISPR defenses. However, the new research suggests this isn’t the case. This implies that gut bacteria may encounter viruses less often than assumed or depend on alternative forms of protection. The findings also have implications for microbiome-based therapies, such as probiotics or fecal transplants, by showing that CRISPR may not be the primary defense mechanism in the gut.

Lead author An-Ni Zhang of the Cell Genomics paper explains the outcome: “We discovered that it takes about 2.7 to 2.9 years for a bacterial species to acquire a single new spacer [a piece of viral DNA] in the human gut. This is unexpected because our gut encounters viruses daily, both from the existing microbiome and our food.” One explanation for this slow rate is the “dilution effect.” When we eat or drink, bacteria and viruses get flushed through the digestive tract, reducing the likelihood of a sustained phage infection event that would trigger new CRISPR updates — much less often than in tightly controlled laboratory conditions.

Borrowed CRISPR

The study also highlights another way gut bacteria can acquire defenses: horizontal gene transfer (HGT). HGT enables bacteria to share genetic material directly, including full CRISPR defense systems. Instead of building their arsenal piece by piece, some bacteria — such as Bifidobacterium longum —can gain pre-made CRISPR arrays through HGT. The researchers note, “We identified a highly prevalent CRISPR array in Bifidobacterium longum spreading via horizontal gene transfer (HGT), with six spacers found in various genomic regions in 15 persons from the United States and Europe.” These “borrowed” CRISPR systems equip B. longum with defenses against certain viruses more quickly than if they had to add spacers one at a time.

Gut virus protection

“It has been highly overlooked how much horizontal gene transfer contributes to this dynamic. Within communities of bacteria, the bacteria-bacteria interactions can be a main contributor to the development of viral resistance,” the authors write. Because HGT can bundle multiple virus-targeting segments in one transfer, it multiplies the number of new defense elements a bacterium gains. This finding raises questions about how much of a species’ CRISPR evolution happens slowly in-house versus how much arrives wholesale from neighbors. In therapeutic contexts, it also suggests that working with or engineering strains that already carry robust CRISPR arrays could be a strategic way to protect against gut viruses.

These results show that while CRISPR is a powerful bacterial defense system, its real-world behavior in the human gut can be surprisingly gradual. Dilution events and horizontal gene transfer affect how often new spacers appear. For researchers and clinicians, acknowledging the slow pace of in-gut CRISPR adaptation — and the outsized role of “borrowed” CRISPR arrays — could inform future approaches to probiotics and fecal microbiota transplants. By better understanding these dynamics, we can more accurately anticipate how bacteria evolve and survive in one of the body’s most complex microbial ecosystems.