When microbiomes collide

A team of researchers led by the Bork group at EMBL Heidelberg, along with their collaborators in the Netherlands and Australia, have now used this unusual medical technique to ask an intriguing question: What happens when two gut microbiomes mix?

The answer could provide clues to better therapeutic strategies for gut diseases, as well as a fuller understanding of how microbial species behave and interact in complex natural ecosystems.

transplant microbes

Although clinical studies have shown that FMTs can effectively treat certain gut disorders, how they work remains unclear. Some theorize that the gut microbiomes of donors have beneficial properties that help restore the recipient’s gut to a healthy state. However, this has never been systematically studied.

“The ‘super donor’ hypothesis is widespread among practitioners: it postulates that the search for ‘good’ donors is crucial for the clinical success of FMT and that one good donor works for many different patients,” said Sebastian Schmidt, one of the first authors of a new study published in naturopathy.

However, using clinical and metagenomic data from over 300 FMTs, the researchers discovered that it is likely the recipient rather than the donor who primarily determines the microbial mix resulting from this procedure. This builds on a 2016 study by the Bork group, which showed that microbial strains from a donor can coexist with those from a recipient with metabolic syndrome.

The team developed a machine learning approach to analyze the factors that determine microbial dynamics after FMT, including the presence or absence of individual microbial species. Their results show that species richness (a measure of how diverse a recipient’s gut microbiome was before transplantation) as well as the difference between a recipient’s gut microbiome and that of a donor are both important factors in determining which species survive and after a transplant will thrive.

An ecological experiment

Simone Li, another first author of this and the 2016 study, finds their findings intriguing from an ecological perspective. “Thriving and surviving in a completely new environment is not an easy task, especially in a dynamic environment like the human gastrointestinal tract, where there are constant changes in acidity, oxygen levels, and nutrients, among other things,” she said . “As we move toward safer options of microbiome-based therapeutics, what goes in is only as important as whether they stay long enough to deliver the intended benefit.”

By treating FMT procedures as ecological experiments, in which entire microbial ecosystems are displaced to new locations with pre-existing ecosystems, the researchers were able to draw important conclusions about what factors help decide how well or easily bacteria will thrive in new ones Can “colonize” environments.

As Peer Bork, the study’s corresponding author, points out, this could also have important practical applications. “As our understanding of the ecological processes in the gut after FMT improves, we may discover more precise and targeted links to clinical effects – for example, to crowd out only certain strains (e.g. pathogens) while ‘collateral’ effects on the remainder of the microbiome.”

Although the study primarily looked at bacteria and archaea, which together make up over 90% of the gut microbiome, the researchers hope future studies may also include data from fungi, other eukaryotes, and viruses to get a more holistic view of the process.

“I hope (and am confident) that our results will help design more effective FMT protocols in the future. We provide data on which parameters are worth adjusting (and which are not) when aiming to modulate the recipient microbiome. In the long term, this may also inform the design of next-generation personalized probiotic treatments,” said Schmidt.