How gene-edited microbiomes could improve our health

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Microbes have been on my mind this week. These tiny organisms are everywhere, and the ones that reside in our bodies appear to be incredibly important for our health.

Microbes are ancient-they were evolving on the planet for millions of years before humans came along. So it's no surprise that they've developed intricate relationships with other living systems. They feed on chemicals in their environments to produce other chemicals-some of which are more beneficial to nearby organisms than others.

The question is: can we tweak the genomes of these microbes to control exactly which chemicals they break down or produce? Imagine the possibilities. What if we could get microbes to help us reduce pollution? What if we could create microbes that make medicines, or that churn out gut-friendly products in our intestines?

Modified microbes seem to help treat cancer in mice, and human trials are on the way, as I reported earlier this year. (For a more general update on gene editing, you can read about how the editing tool CRISPR is already changing people's lives, and how some believe we'll eventually be using the technology to treat the majority of people.)

Getting microbes to work for us has been a tantalizing prospect to scientists for decades. New technologies are bringing us ever closer to making it a reality. So for this week's newsletter, let's focus on a couple of particularly exciting ways people are engineering microbes to benefit our health and environment.

Take the work being done by Brad Ringeisen, executive director of the Innovative Genomics Institute in Berkeley, California, and his colleagues. The team recently received a huge amount of funding to explore new ways to engineer microbes for the well-being of people and the planet-particularly people living in low- and middle-income countries.

We got $70 million to develop precision microbiome-editing tools," says Ringeisen. The team is focusing on using CRISPR to change the behavior of microbes-not just bacteria, but also their lesser-studied co-habitants, such as fungi and archaea. The idea is that feeding such treatments to people or animals could get their gut microbiomes to a healthier state.

The likely first recipients of such treatments will be cows. The way we farm these animals has a tremendous impact on the environment, for several reasons. (Read more from Tech Review about what it would take to clean up farming here and here.) But one significant element is the methane they emit, since methane is a powerful greenhouse gas that contributes to climate change.

Technically, the methane isn't made by the cows themselves. It's produced by archaea in their guts. Ringeisen and his colleagues are looking at ways to alter microbes that reside in the rumen-the first and largest stomach compartment-so that they produce much less of the gas, if any.

Ringeisen thinks that modifying existing microbes should be less disruptive than introducing entirely new ones. He likens the approach to that of a conductor fine-tuning the sound of an orchestra. [It would be like] bringing up the violin and lowering the bass drum, but to tune the microbiome," he says.

The team is also looking at how a CRISPR microbiome treatment might benefit human infants. A baby's first microbiome-thought to be picked up at birth-is especially malleable during the first two years of life. So microbiologists believe it's important to get an infant's microbiome as healthy as possible early on.

We still don't know exactly what that means, or what a healthy microbiome should look like. But ideally, we want to avoid having bugs that make chemicals that cause harmful inflammation or damage the gut lining, for example. And we might want to encourage the growth of microbes that make chemicals that aid gut health-like butyrate, which is made when some microbes ferment fiber and seems to strengthen the intestine's natural barrier.

The work being done here is still in its early stages. But the researchers envision an oral treatment that would be fed to babies to manipulate their microbiomes. They don't have a specific age in mind, but it could be quite soon after birth.

As long as the modified microbes aren't making anything harmful, it should be relatively straightforward to approve these treatments, says Ringeisen. Those are experiments that are going to be relatively easy to do," he says.

Justin Sonnenburg, a professor of microbiology and immunology at Stanford University in California, is also looking at ways to reengineer the microbes in our guts to improve our health. One important target is inflammation-a process that has been linked to all sorts of diseases, ranging from arthritis to cardiovascular disease.

Microbes that live in our guts can sense inflammation, says Sonnenburg. If we could rewire the genetic circuit" of these microbes, we could potentially enable them to secrete anti-inflammatory compounds that treat inflammation if and when it arises. All this [would be] happening behind the scenes without the person harboring the microbes even knowing about it," he says.

One of the challenges will be to develop a treatment that works the same way in different people, who will have different microbiomes. But there may be some ways around this. In a study a few years ago, Sonnenburg and his colleagues delivered a modified microbe into the guts of mice. This microbe glowed under a microscope, so the scientists could tell how well it had settled in the mice's intestines. It was quite variable-some of the mice had more of the microbes than others.

This particular microbe also fed on a carbohydrate found in seaweed, called porphyran. And when the scientists fed the mice seaweed, they found they could influence levels of the microbe in the gut. A diet rich in seaweed brought up the levels in all the mice, for example. Now we have the ability to control engraftment and the level of the microbe independent of the background microbiota," says Sonnenburg.

Some of the scientists who worked with Sonnenburg on this study have since formed a company, called Novome, which has shown that it can achieve similar results in people. The company is working on a proprietary microbial strain that has been engineered to break down oxalate, a compound that contributes to the formation of kidney stones. The company is also working on engineered microbes for irritable bowel syndrome and inflammatory bowel disease.

Scientists have been working on designer microbes" for decades. But the progress made in recent years has brought such treatments closer to reality. Ringeisen reckons we're four to six years away from a human treatment, and he thinks cow treatments are even closer than that. It's an exciting time. Let's wait and see.

Read more from Tech Review's archive

About 60 million metric tons of food waste is generated every year in the US alone. My colleague Casey Crownhart wrote about one company trying to use microbes to help digest" it.

Engineered microbes are also being explored as a new way to make cheaper and cleaner fuels, as Casey reported last year.

Your microbiome ages as you do-and that's a problem. Scientists are trying to work out whether tweaking our microbiomes could help keep us healthy in old age.

Feel like you could do with some personalized, microbiome-based diet advice? Your poo could provide a rich source of such information.

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Correction: The methane produced in cows' guts is made by archaea, not bacteria.