Scientists Develop Tool To Show How Our Microbiome Changes Over Time
The microbiome has been the topic of much conversation over the last few years And for good reason! We already know that it affects so many aspects of our health: everything from our energy levels and our mood to our weight and blood sugar balance is affected by the specific bacteria we have in our guts. It's clearly one of the main drivers of optimal health and well-being.
And yet, there's still so much we don't know. One reason for this is that it's proved difficult to observe how the microbiome changes over time—especially in response to specific treatments or stimuli—with an appropriate level of detail. Luckily, a new study, published in Nature Communications, introduces a tool that may help.
Why we need better methods for observing changes in the microbiome.
Currently, we analyze the microbiome by way of fecal samples. Scientists take those samples, extract the bacteria living in them, and then sequence the genomes of those bacteria. This is how we've been able to associate gut microbial changes with illnesses like lupus and obesity.
So what's the problem then? While stool samples are minimally invasive, they don't provide important information such as where the specific bacteria are in the gut and when, exactly, changes in the gut occur. The result is a general idea of what happens in the microbiome but not an exact series of events, which brings us to...
Meet the repressilator: a new way to study gut health.
The new tool introduced in the study, called a repressilator, solves exactly this problem. Developed by researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard Medical School, the repressilator contains three bacterial genes that code for specific repressor proteins, which are linked together into a negative feedback loop. This all gets very complicated very fast, but essentially, when the concentration of one of the repressor proteins becomes low, the protein it was repressing in the feedback looped is expressed, which then blocks the expression of the third protein in the loop. This cycle repeats itself over and over, acting as a tool that measures bacterial growth with single-cell precision.
If you find this difficult to wrap your head around, you're not alone. Just remember that the bacterial genes in the repressilator have been engineered to detect and record changes in the population of bacteria in the microbiome over time with an incredible level of detail. "This repressilator allows us to really probe the intricacies of bacterial behavior in the living gut, not only in both healthy and diseased states, but also spatially and temporally," said corresponding author Pamela Silver, Ph.D. It also means "that we can study the microbiome in a more natural state with minimal disruption," she continued.
How to understand the microbiome on a whole new level.
To put the tool to the test, the authors of the study administered specific bacteria containing the repressilator circuit to mice. The results showed that the tool remained active for up to 16 days and successfully detected changes in bacterial growth. Next, they gave half of the mice an inflammation-inducing compound, followed by the repressilator. After 15 hours, the mice given the inflammatory compound showed corresponding changes in the repressilator activity, confirming that inflammation produces environmental changes in the gut microbiome and that the repressilator can measure them.
So what does this mean for us humans? "Not only does this research solve a specific problem related to monitoring dynamic changes in microbiome physiology within the living gut, it provides a platform that could lead to entirely new types of diagnostics and even time-dependent therapeutics," said Donald Ingber, M.D., Ph.D., founding director of the Wyss Institute.
In other words, this tool could help us diagnose gut issues with more accuracy, develop better treatments (like specific probiotics), and then measure the effects of those treatments with a level of detail we haven't previously had. Knowing just how many of us have health conditions related to microbiome imbalance, the applications are almost endless.
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