What is it?
ResoreGut is the world’s first randomized clinical trial using fecal microbiota transplantation (FMT) and fecal virome transplantation (FVT) to restore the microbiome in children born by cesarean section.
Why do we do it?
Early-life microbiome composition is very important for the long-term development of the host immune system. In our COPSAC cohorts, we have found that children born by cesarean section have a significantly higher risk of developing asthma in childhood. We have also seen that cesarean section leaves a characteristic microbial “fingerprint” on the gut microbiome. Most cesarean section-delivered children normalize their microbiome during the first year of life; however, the continued presence of this fingerprint one year after birth is a powerful predictor of future childhood asthma. We believe that this fingerprint can be erased by early intervention and that doing so can reduce the risk of asthma.
The main microbial difference between children born vaginally and by cesarean section is exposure to an assortment of bacteria from the mother during birth. Previous experiments with seeding vaginal bacteria from the mother have been performed; however, the bacteria most responsible for colonizing the child’s intestine are not from the vagina but rather fecal bacteria from the mother’s intestine making vaginal seeding less effective.
What is the Goal?
The aim of the study is to investigate whether we can normalize the gut microbiome and eliminate the increased risk of asthma associated with birth by cesarean section.
How is it done?
In RestoreGut, we want to mimic the microbial exposures of a vaginal birth by transferring a tiny amount of maternal fecal matter (FMT) to children born by cesarean section. We then compare the microbiome development against a control group of cesarean section-born children receiving a placebo treatment as well as a group of children born vaginally. We will also investigate the ability of bacteria-specific viruses (bacteriophages or phages) to shape the bacterial composition through our FVT intervention. Our collaborators have demonstrated a great potential for FVT, which benefits from the fact that phages do not infect human cells like certain bacteria can, perhaps eliminating the extensive safety screening required for FMT donors. In RestoreGut, we will test the efficacy of this promising alternative to bacterial transfer for a more widely available therapeutic tool. All maternal donor samples will undergo extensive safety screening.
Who is involved?
RestoreGut is an innovative collaboration among several expert institutions: COPSAC, the University of Copenhagen, Rigshospitalet, and Hvidovre Hospital. This project is under the expert guidance of principal investigator, associate professor, and senior researcher Jakob Stokholm. He oversees the trial’s operations alongside Ph.D. student Kaare Tranæs. They work in close partnership with Nina Olsén Nathan, a midwife and Ph.D. student from Rigshospitalet.
Leading the Clinical Microbiology unit at Hvidovre Hospital are Senior Resident Morten Helms and Researcher Hengameh Chloe Lauridsen. They contribute their significant expertise to the project, perform safety screening of the donor material, and prepare the intervention transplants.
The project is funded through a European Research Council (ERC) consolidator grant.
Do you want more information?
Contact:
Kaare Tranæs – PhD Student
Jakob Stokholm – Senior researcher, MD, PhD
