New research at UCLA has led to significant findings on DNA guide RNAs (DGRs). Together, these findings reaffirm an important role for DGRs in the context of intestinal microbiomes. We found that DGRs are much more prevalent in the human gut than in any other environment we’ve studied so far. This discovery, made in the laboratory of Jeff F. Miller, sheds light on how these molecules facilitate bacterial adaptation, particularly during the crucial first year of life for newborns.
The study underscores that DGRs serve an important niche role in the genetic repertoire of bacteria. Specifically, they substitute the letter A in DNA’s four-letter alphabet with a C, G or T. This change permits the bacteria to quickly adjust to their environment, helping their colonization tactics in a new locale. In their search, researchers found that bacterial populations have a surprisingly high richness of DGRs. On average, one DGR exists per strain, though some strains can have up to five.
The Role of DGRs in Microbiome Development
In this new work, the UCLA team took a closer look at samples from moms and their children throughout infancy. Their goal was to better understand the effects of DGRs on the gut microbiome. In fact, during this important development window, the gut microbiome is just beginning to take shape. DGRs are a key part of this development.
The research mainly used the gut-dwelling Bacteroides species—which are some of the most prevalent gut bacteria. The researchers discovered that approximately one-quarter of the DGRs identified target genes essential for bacteria to anchor themselves and form colonies in new environments. This superpower to cling to any surface helps bacteria to survive in the harshest environments.
“The developing microbiome is connected to our developing immune system, and that primes us for the rest of our lives,” – Ben Macadangdang
Through their investigation, the researchers discovered over 1,100 distinct DGRs. These results provide evidence that these factors are important modulators for determining the developing microbiome in infants. DGRs don’t just make bacteria more fit, they play a role in creating the distinct, overall composition of gut flora found in newborns.
Horizontal Transfer and Adaptation
Arguably the most astounding thing about DGRs is their potential for horizontal transfer. This process gives DGRs the ability to quickly jump from one bacterium strain to the next, making rapid evolutionary adaptations possible. Consequently, DGRs allow bacteria to change the proteins on their pili—hair-like appendages used for sticking.
“We think DGRs allow the bacteria to rapidly change what their pili can adhere to,” – Ben Macadangdang
This ability is especially key because it is with this strain that bacteria can rapidly adapt to new habitats. This rapid evolutionary process provides them the best chance of survival and allows them to maintain and strengthen their resource within the gut microbiome.
Looking forward, the authors highlight the potential of DGRs to inform new applications and discoveries in microbiome research. Jeff F. Miller remarked on the significance of these findings, stating, “There are so many questions that this raises, we’re just realizing how much we don’t know about DGRs in the [microbiome], or what exploiting them for applications could yield. I’ve never been more excited about what’s going to come next.”
Implications for Future Research
The implications of this research go far beyond an interest in the practice of microbial life. The findings suggest that DGRs may be integral to understanding how bacteria colonize hosts and establish themselves within the microbiome. Gut health is at the center of our overall health. By continued investigation of DGRs, toxicological studies have the potential to greatly increase our understanding of human health and work to prevent disease.
As the understanding of DGRs develops, researchers are hopeful that future studies will explore their potential applications in various fields, including medicine and biotechnology. Though over 1,100 DGRs have been described so far, we have only begun to scratch the surface in understanding their functions and capabilities.