Studies on the gut microbiome showed that the collection of hundreds of bacteria inside the human digestive system could influence cancer immunotherapies, neural development, and many aspects of a person's health. Stanford University researchers created the most complex, well-defined synthetic microbiome to know the exact cells and molecules linked with certain diseases.
Phys.org reported that the team's synthetic microbiome is a community of over 100 bacterial species successfully transplanted into mice. Scientists will be able to better understand the links between the microbiome and health through this and eventually create first-in-class microbiome therapies.
How They Built the Synthetic Microbiome
The team had to ensure that the final mixture was stable to maintain balance without any species overpowering other species and also ensure that it was functional in performing the actions of a natural microbiome. Also, they noted that it is challenging to select which species to include in their synthetic microbiome since each person could not have the same microbiome components.
In their study, titled "Design, Construction, and In Vivo Augmentation of a Complex Gut Microbiome," published in the journal Cell, researchers reported building their synthetic microbiome from the most prevalent bacteria. They turned to the Human Microbiome Project (HMP) of the National Institutes of Health (NIH) to sequence the full microbiome of 300 adults.
The study's corresponding author Michael Fischbach, an Institute Scholar at Sarafan ChEM-H, said that they are looking for the Noah's Ark of bacterial species in the human gut microbiome to find which were almost always present in any person.
In the end, they selected 100 bacterial strains found in at least 20% of the HMP individuals and added a few species for some subsequent studies, making it a total of 104 species that grow in individual stocks. Then the team mixed their synthetic microbiome into one collaborative culture to make the human community one (hCom1).
They transplanted hCom1 into mice without bacteria and found that hCom1 was remarkably stable, with 98% of the constituent species colonizing the gut of the mice and remaining constant for over two months.
Most Complex, Well-Defined Synthetic Microbiome Could Help Scientists Study Which Molecules Are Linked to Certain Diseases
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Testing the Ark
Researchers tested their ark by introducing the synthetic microbiome into an existing colony to see whether it would survive or not. This step is crucial as it will show how vital the microbiome functions and gain insights into building a complete community.
Fischbach said in a press release that the bacterial species in hCom1 only survived together for a few weeks, so introducing them into a community that had coexisted for a decade could be a challenge. Some even believe that it would decimate hCom1.
But surprisingly, it held its own, and only 10% of its cells in the final community came from the fecal transplant. The team found 20 new bacterial species inserted in at least two of three fecal transplant studies. In total, they ended up with 119 strains, now dubbed the hCom2, made from individually growing and mixing the constituents and made mice more resistant to digestive diseases.
The final challenge is to demonstrate the use of synthetic microbiomes. The team used the mice with hCom2 and tested them with a sample of E. coli. They found that the mice were able to resist the infection.
Previous studies showed that a healthy natural microbiome provides protection. The team believes they could take this step further by eliminating or modifying some strains to know which one gives more protection. They identified several bacteria and plan to conduct further studies on them in the future.
In conclusion, Fischbach believes that hCom2 and its future versions will lead to new discoveries of which bacterial agents are involved in certain areas of health and the development of microbiome-based therapies in the future.
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