Cross-generational bacterial strain transfer to an infant after fecal microbiota transplantation to a pregnant patient: a case report

Abstract

Background: Fecal microbiota transplantation (FMT) effectively prevents the recurrence of Clostridioides difficile infection (CDI). Long-term engraftment of donor-specific microbial consortia may occur in the recipient, but potential further transfer to other sites, including the vertical transmission of donor-specific strains to future generations, has not been investigated. Here, we report, for the first time, the cross-generational transmission of specific bacterial strains from an FMT donor to a pregnant patient with CDI and further to her child, born at term, 26 weeks after the FMT treatment.

Methods: A pregnant woman (gestation week 12 + 5) with CDI was treated with FMT via colonoscopy. She gave vaginal birth at term to a healthy baby. Fecal samples were collected from the feces donor, the mother (before FMT, and 1, 8, 15, 22, 26, and 50 weeks after FMT), and the infant (meconium at birth and 3 and 6 months after birth). Fecal samples were profiled by deep metagenomic sequencing for strain-level analysis. The microbial transfer was monitored using single nucleotide variants in metagenomes and further compared to a collection of metagenomic samples from 651 healthy infants and 58 healthy adults.

Results: The single FMT procedure led to an uneventful and sustained clinical resolution in the patient, who experienced no further CDI-related symptoms up to 50 weeks after treatment. The gut microbiota of the patient with CDI differed considerably from the healthy donor and was characterized as low in alpha diversity and enriched for several potential pathogens. The FMT successfully normalized the patient's gut microbiota, likely by donor microbiota transfer and engraftment. Importantly, our analysis revealed that some specific strains were transferred from the donor to the patient and then further to the infant, thus demonstrating cross-generational microbial transfer.

Conclusions: The evidence for cross-generational strain transfer following FMT provides novel insights into the dynamics and engraftment of bacterial strains from healthy donors. The data suggests FMT treatment of pregnant women as a potential strategy to introduce beneficial strains or even bacterial consortia to infants, i.e., neonatal seeding. Video Abstract.

Keywords: Clostridioides difficile infection; Engraftment; Fecal microbiota transplantation; Gut microbiota; Infant; Neonatal seeding; Pregnancy; Strain transfer.

Fig. 1

Timeline indicating vancomycin treatment, FMT, sampling time points for the mother and infant. Sampling time was relative to FMT (for the patient) or time of birth (for the infant). Colors indicate samples from donor (red), patient (blue, with samples taken before FMT (P-pre-FMT) and at 1, 8, 15, 22, 26, and 50 weeks after FMT), infant (green, with samples taken at birth (I0m) and at 3 and 6 months after birth), and an independent donor not used for the specific FMT (yellow). The patient vaginally delivered a healthy child at term, i.e., 26 weeks after the FMT

Fig. 2

Gut microbiota compositional differences between the donor, patient, and infant. A Alpha diversity (observed richness and Shannon diversity) for all subjects. B Beta diversity of all subjects based on the Bray-Curtis distance and visualized with principal coordinates analysis (PCoA). C The taxonomic composition for the top 20 families. Less abundant families were merged as “Others.” Fecal samples were collected from the donor and an independent (not-used) donor as well as from the patient during active CDI before the fecal microbiota transplantation (P-pre-FMT) and at 1 week (P1w), 8 weeks (P8w), 15 weeks (P15w), 22 weeks (P22w), 26 weeks (P26w, at term), and 50 weeks (P50w, 6 months after giving birth) after the FMT. Fecal samples were collected from the infant at birth (I0m, meconium), 3 months old (I3m), and 6 months old (I6m)

Fig. 3

Transfer of donor microbes to the patient, estimated at the species level. A The Bray-Curtis distance between the patient and the donor or the independent (not-used) donor over time. B The proportion of species common to the patient and the donor or independent donor over time. C Contributions to the patient post-FMT gut microbiota. Possible sources were divided into four categories, namely donor-specific (species from the donor and not shared with the patient pre-FMT), shared (species common to donor and the patient pre-FMT), recipient-specific (species from the patient pre-FMT and not shared with the donor), and newly detected (species not included in the above categories, possibly from the environment or below the detection limit). Line types indicate the measurement was performed with the donor (solid) or the independent donor (dashed). Fecal samples were collected from the donor and an independent (not-used) donor as well as from the patient during active CDI before the fecal microbiota transplantation (P-pre-FMT) and at 1 week (P1w), 8 weeks (P8w), 15 weeks (P15w), 22 weeks (P22w), 26 weeks (P26w, at term), and 50 weeks (P50w, 6 months after giving birth) after the FMT

Fig. 4

Transmission of donor strains to the patient and maternal transmission to the infant. A The proportion of donor and pre-FMT patient strains from four different species detected in the infant at birth and 3 and 6 months after birth, based on discriminative positions. B The phylogenetic tree for HG4D.0018—Eubacterium rectale containing 246 strains identified from publicly available adult and infant samples from healthy Danes. Donor and patient samples are highlighted in blue and red, respectively. The phylogenetic tree highlighted in the box is the zoom of the bigger tree. C Detection of donor strain in patient and infant samples across 120 different species based on the percentage of identical alleles between strains identified in the donor and in the patient or infant samples. Fecal samples were collected from the FMT donor and an independent (not-used) feces donor as well as from the patient during active CDI before the FMT (P-pre-FMT) and at 1 week (P1w), 8 weeks (P8w), 15 weeks (P15w), 22 weeks (P22w), 26 weeks (P26w, at term), and 50 weeks (P50w, 6 months after giving birth) after the FMT. Fecal samples were collected from the infant at birth (I0m, meconium), 3 months old (I3m), and 6 months old (I6m)