Fecal microbiota transplantation (FMT) — the transfer of lower intestinal fluids and microbes from one individual to another — is sometimes used to treat inflammatory bowel diseases, including ulcerative colitis and bacterial infections. Although a form of it was first recorded in 4The tenth Century China, it was introduced to Western medicine in the 1950s. In the past two decades, it has steadily gained prominence.
A team of researchers led by the Bork group at EMBL Heidelberg, along with their collaborators in the Netherlands and Australia, used this unusual medical procedure to ask a fascinating question – what happens when two gut microbiomes mingle together?
The answer could hold clues to better treatment strategies for gut disorders as well as a richer understanding of how microbial species behave and interact in complex natural ecosystems.
culture of microbes
Although clinical trials have shown that FMTs can effectively treat some bowel disorders, how they work remains unclear. Some hypotheses posit that the gut microbiomes of donors have beneficial properties that help restore the recipient’s gut to a healthy state. However, this has not been studied systematically.
“The ‘super-donor’ hypothesis is widespread among practitioners: it posits that finding ‘good’ donors is essential to the clinical success of FMT and that a good donor will work with many different patients,” said Sebastian Schmidt, one of these. The first authors of a new study published in Nature medicine.
However, using clinical and metagenomics data from more than 300 FMTs, the researchers discovered that it is likely the recipient rather than the donor that primarily determines the microbial mix resulting from this procedure. This is based on a 2016 study from the Burke group that showed that microbial strains from a donor can co-exist with strains from a recipient with metabolic syndrome.
The team developed a machine learning approach to dissect 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 the recipient’s gut microbiome is prior to transplant), as well as how different the recipient’s gut microbiome is from the donor’s, are both key factors in determining which species will survive and thrive after transplant. .
Simone Li, the other first author of this study and the 2016 study, found their results fascinating from an environmental perspective. “Being able to thrive and survive in an entirely new environment is not an easy task, especially in a dynamic environment like the human digestive system, where there are constant changes in acidity, oxygen levels, and nutrients, among other things,” she said. “As we move toward safer options for microbiome-based therapies, what is introduced only matters if it stays long enough to deliver the desired benefits.”
By treating FMT procedures as ecological experiments where entire microbial ecosystems are replaced by new sites with pre-existing ecosystems, researchers can draw important conclusions about factors that help determine how easily or easily bacteria can colonize new environments.
As Per Burke, the study’s corresponding author, points out, this may also have important practical applications. “As our understanding of environmental processes in the gut following FMT improves, we may discover more subtle and more targeted links to clinical effects—for example, to replace only certain strains (such as pathogens) while reducing ‘side effects’ to the rest of the microbiome.”
Although the study primarily looked at bacteria and archaea, which together make up more than 90% of the gut microbiome, the researchers hope that future studies may also include data from fungi, other eukaryotes, and viruses to get a more comprehensive view of this. to treat.
“I hope (and am confident) that our findings 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 modify the recipient microbiome. Over the long term, this may be Also a resource for designing “next-generation” personalized probiotic treatments,” Schmidt said.