The human gut is an unexplored universe. Up to a trillion bacteria live there, spread over several hundred species. They are not only important for nutrition, but also have an impact on aging and diseases such as dementia, autism and heart attacks. But it is difficult to decipher exactly which intricate paths this so-called “microbiome” uses to interact with the body.
Stanford researchers have therefore now chosen a different approach: instead of trying to understand the chaotic ecosystem in the digestive tract as a whole (“top-down”), they built it from scratch (“bottom-up”). By adding, changing or omitting certain bacteria in a targeted manner, they want to better understand the complex relationships.
The artificial microbial cocktail not only had to perform the same function as natural bacterial colonization, for example breaking down certain food components. Its composition also had to remain stable – the strains were not allowed to crowd each other out.
Extrem diverses Mikrobiom
Nature was only of limited help in finding the right recipe: “Two randomly selected people share less than half of their microbiome genes,” writes Stanford University. In order to get close to the right mixture, Professor Michael Fischbach’s team used the data from the Human Microbiome Project, which sequenced the microbiome genes of more than 300 test subjects. From this, they selected the bacterial species that were present in at least 20 percent of the test subjects.
The researchers came up with a total of 104 strains, which were initially bred separately in the laboratory. They were then implanted in a precisely defined mixing ratio in the previously sterilized intestines of mice. The result: 98 percent of the species settled, and even after two months their relative relationship to one another remained constant.
The next test should check how robust the artificial colony is to invaders. According to theory, new bacteria should only be able to gain a foothold in a functioning microbiome if they take over functional niches that were previously unoccupied. To test this theory, the researchers introduced human stool samples into the intestines of the test animals – i.e. a bacterial community that had previously proven itself for years. “Some observers thought that would decimate their own colony,” says Fischbach. But that was not the case: At the end of the experiment, only around ten percent of the species came from the stool transplant.
treatments against diseases
In the next round of experiments, the research team dropped the failed strains and incorporated the newly arrived ones into their synthetic microbiome, which now comprised 119 strains. The mice thus proved to be even more resistant to infection by foreign strains, such as pathogenic Escherichia coli germs. Otherwise, the mice with an artificial microbiome behaved in exactly the same way as test animals with natural intestinal flora.
In further studies, Fischbach and his team now want to narrow down which bacteria are most important for a resistant microbiome. The recipe will also be made available to other research groups. The long-term goal is targeted microbiome treatments against infections, cancer, obesity or neuro-diseases. At present, the entire stool of healthy people is transplanted as a general therapy.
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