2023-08-03 21:03:15
Small organisms called ‘microorganisms’ exist everywhere, and in particular, the microorganisms that live in our bodies seem to play a very important role in our health.
Microorganisms are ancient life forms that have evolved millions of years before humans appeared in Earth’s history. So it is not surprising that microbes have forged complex relationships with other life forms over the ages. Microorganisms digest chemicals in their environment and then produce other chemicals, which sometimes benefit other organisms nearby.
The question is whether microbial genes can be manipulated and precisely controlled to break down or produce specific chemicals. Let’s consider several ways to use it. What if this technology might make microorganisms that reduce environmental pollution? Or what if we developed microbes that produce therapeutic drugs or substances beneficial to gut health in the gut?
In early 2023, I wrote an article that genetically engineered microbes might help treat cancer in mice. Now, the technology is in the process of human clinical trials. (Previously, MIT Technology Review related to gene editing technology, how treatments using CRISPR gene editing technology are already changing people’s lives, and why some believe that this technology will ultimately cure the majority of people. It tells the story of what it claims to be used for.)
Over the past few decades, scientists have been interested in the potential use of microbes to benefit humans. With the advent of new technologies, this prospect is gradually becoming a reality. In the MIT Technology Review, we will focus on some of the ways to use microbial engineering to benefit our health and the environment.
Take, for example, research conducted by Brad Ringeisen, director of the Innovative Genomics Institute at the University of California, Berkeley, and his colleagues. Recently, the research team received extensive research funding to explore new techniques of microbial engineering for the health of people and the planet, especially in low- and middle-income countries.
“We received 70 million dollars (approximately 90.1 billion won) to develop precision gene editing technology targeting the microbiome,” says Ringeisen. The research team is focusing on using CRISPR to change the behavior of symbiotic microorganisms, including not only bacteria, but also relatively understudied fungi and archaea. These treatments arose from the idea that ingesting microbes in humans or animals would make the gut microbiome healthier.
Cattle are likely to be the first beneficiaries of treatments using genetically engineered microbes. Cattle breeding has a very large impact on the environment in many ways. One of the most important is the methane emitted by cows, because methane is a component that contributes to climate change by causing a strong greenhouse effect.
Strictly speaking, methane is not made by cows. Methane is produced by archaea in the intestines of cattle. Ling Geisen and his colleagues are exploring how to change the microbes that live in the rumen, the first and largest of cattle’s four stomachs, to produce much less methane gas.
Ringeisen believes that the impact of modifying existing microbes will be less than introducing entirely new microbes. He likens this approach to the role of a conductor in an orchestra, fine-tuning the notes of the instruments. “In the same way that a conductor can turn up a violin, turn down a bass drum, or tune an orchestra, this technology tunes the microbiome,” he says.
The team is also exploring how genetically engineered microbiome therapies using CRISPR might help infants. It is generally known that a baby’s first microbiome is formed at birth, but the first two years of life are particularly variable. Therefore, microbiologists believe it is important to make the infant’s microbiome healthy as early as possible.
At this time, it is not known exactly what a healthy, ideal microbiome would look like. However, in theory, you should avoid microbes that release chemicals that cause harmful inflammation or damage the intestinal lining. Conversely, stimulating the growth of microorganisms that produce chemicals beneficial to gut health is one way. For example, butyrate, a substance produced when some microorganisms ferment fiber, is known to strengthen the natural intestinal lining.
The ongoing research is still in its infancy. But researchers are envisioning ways to manipulate babies’ microbiome through oral therapies. We don’t have a specific age in mind, but it might be right following birth.
As long as genetically engineered microbes don’t produce harmful substances, it will be relatively easy to get approval for treatment from authorities, Ringeisen explains. “These experiments are relatively easy to perform,” he says.
Justin Sonnenburg, professor of microbiology and immunology at Stanford University, is researching ways to improve health by improving the gut microbiome. Its main target is inflammation. This is because inflammation is a common factor in all diseases, from arthritis to cardiovascular disease.
Sonnenberg says the microbes that live in the gut can sense inflammation. If we might ‘change the genetic circuitry’ of these microbes, we might make them secrete anti-inflammatory substances when the body is inflamed. “The whole process will go on silently, without people knowing what is going on in their intestines,” he says.
Now the problem is to make the same effect appear when the same treatment is given even though the microbiome is different for each person. There are several clues regarding this. A few years ago, Sonnenberg and his colleagues experimented with injecting genetically engineered microbes into the intestines of mice. In addition, the degree of engraftment of the microorganisms in the intestines of mice was investigated by observing the fluorescent substances in these microorganisms with a fluorescence microscope. The results showed an inhomogeneous pattern, with some mice harboring more microbes than others.
Among the food the microorganisms used in this experiment was porphyran, a carbohydrate derived from algae. Using this, the researchers found that by feeding seaweed to mice, they might affect the levels of microbes in their gut. For example, mice that ate a lot of seaweed had higher levels of microbes than mice that didn’t. “Now, whatever the existing microbial composition, we can control the engraftment and numbers of microbes,” says Sonnenberg.
Some of the scientists who worked on this study with Sonnenberg later founded a company called Novome that found similar results in humans. Novom is researching special strains of microorganisms genetically engineered to break down oxalate, a compound that causes kidney stones. The company is also working on microbes for the treatment of irritable bowel syndrome and inflammatory bowel disease. Scientists have been working on designer microbes before. Recently, these efforts have borne fruit, and the development of a treatment is on the verge. Ringeisen predicts that a cure for humans will be ready in four to six years, and a cure for cattle will come much sooner than that. Let’s watch with interest to see what will happen.
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