Microbiome: Better health with gene editing?
Microorganisms are everywhere. The ones that live in our bodies are not only bad for our health – quite the opposite. In fact, they seem to be very important for their preservation, at least when they are in the right place.
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In terms of evolutionary biology, they are ancient – they developed millions of years before humans came into existence on our planet. Therefore, it is not surprising that they have developed intricate relationships with other living systems. They feed on the chemicals around them and produce other chemicals – some of which are useful to other organisms.
The question now is: Can we modify the genomes of these microbes in such a way that we can precisely control which substances they break down and which they produce? What if we could get microorganisms to help us reduce pollution? What if we could create microbes that make medicines or produce extra healthy stuff in our gut?
Modified microbes already appear to help treat cancer in mice. Human trials are on the way. Getting the tiny organisms to work for us has been a tantalizing prospect for scientists for decades. New technologies are now bringing us ever closer to realizing this goal.
Reach goals with microbes
Take, for example, the work of Brad Ringeisen, executive director of the Innovative Genomics Institute in Berkeley, California. The researcher’s team recently received significant funding to explore new ways to evolve microbes for the benefit of the planet and its people, particularly in low- and middle-income countries.
“We received $70 million to develop precision tools for microbiome editing,” says Ringeisen. The team is focused on using CRISPR to alter the behavior of organisms – not just bacteria, but also their lesser-studied cohabitants like fungi and archaea. The idea is to restore the gut microbiome to a healthier state.
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The first recipients of such treatments will probably be cows. The way we raise these animals has a huge impact on the environment for a number of reasons. An important factor is the methane they emit – because methane is a powerful greenhouse gas that contributes to climate change.
Technically, the methane is not produced by the cows themselves. It is produced by the bacteria in your intestines. Ringeisen and his colleagues are looking for ways to change the microbes in the rumen – the first and largest part of the stomach of ruminants – so that they produce much less of the gas or none at all.
Microbiome tune like an orchestra
Ringeisen believes that modifying existing microbes should be less disruptive than introducing entirely new ones. He compares the approach to that of a conductor fine-tuning the sound of an orchestra. “It would be like turning up the violin and turning down the bass drum to tune the microbiome,” he says.
The team is also investigating how CRISPR microbiome treatment could benefit human infants. A baby’s first microbiome—which is believed to have formed at birth—is particularly easy to shape during the first two years of life. Microbiologists therefore consider it important to keep an infant’s microbiome healthy as early as possible.
We still don’t know exactly what that means or what a healthy microbiome should really look like. But ideally, we want to avoid the presence of bacilli that produce chemicals that, for example, cause harmful inflammation or damage the lining of the gut. And we might want to encourage the growth of microbes that produce chemicals that support gut health — like butyrate, which is produced when some microbes ferment fiber and appears to strengthen the gut’s natural barrier.
The work is still at an early stage. However, the researchers envision an oral treatment that could be given to infants to affect their microbiome. They don’t have a specific age in mind yet, but it could be soon after the birth.
Fast Approval?
As long as the engineered microbes don’t produce anything harmful, it should be relatively easy to approve these treatments, Ringeisen says. “These are experiments that will be relatively easy to carry out,” he says.
Justin Sonnenburg, a professor of microbiology and immunology at Stanford University in California, is also looking at ways to alter the microbes in our gut to improve our health. A key target is inflammation—a process implicated in everything from arthritis to cardiovascular disease.
Microbes that live in our guts can detect inflammation, says Sonnenburg. If we could rewire the genetic “circuitry” of these microbes, we could potentially enable them to secrete anti-inflammatory compounds that treat inflammation when it occurs. “All this [würde] happen behind the scenes without the knowledge of the person housing the microbes,” he says.
One of the challenges will be developing a treatment that works the same way in different people who have different microbiomes. But maybe there are some ways to get around this. In a study a few years ago, Sonnenburg and his colleagues introduced a modified microbe into the guts of mice. This microbe glowed under the microscope, allowing the scientists to determine how well it had settled in the mice’s guts. The result was quite variable – some mice had more of the microbe than others.
First cows, then people
This particular microbe also fed on carbohydrates found in seaweed called porphyry. When the scientists fed the mice seaweed, they found they could influence the levels of the microbe in the gut. For example, a diet high in seaweed increased levels in all mice. “Now we are able to control the implantation and levels of the microbe independently of the background microbiota,” says Sonnenburg.
Some of the scientists who worked with Sonnenburg on this study have since started a company called Novome, which has shown it can achieve similar results in humans.
The company is working on a proprietary strain of microbes engineered to break down oxalate, a compound that contributes to kidney stone formation. The company is also working on the development of microbes for irritable bowel syndrome and inflammatory bowel disease.
Scientists have been working on “designer microbes” for decades. But advances in recent years have brought such treatments a little closer to reality. Ringeisen estimates that we are four to six years away from a human treatment. He believes treating cows is even closer than that.
(jl)
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