Text

theses

Caesarean section (CS) is an increasingly common procedure by which the baby is born sterile into the air of the operating room, bypassing the normal exposure to maternal microbiota along with antibiotic exposure leading to altered gut microbiota composition based on birth mode. CS born do not acquire the normal microbiota inoculum at birth, and their microbiota has been shown to be abnormal. We hypothesize that the differences in the human neonatal microbiota lead to different engraftment in germ free mice. To test this hypothesis we aimed to determine microbiota engraftment in sterile mice inoculated with human baby feces discordant to birth mode and the effect of high fat diet (HFD) on the growth and microbiome development. To accomplish these aims we transferred feces from 2 days old human neonates born vaginally (VD) or by CS into 32 germ free (GF)female mice (n=16 in each group)4-6 weeks of age. After 4 weeks post gavage, half of the mice of each group (n=8) were given high fat diet for 5 weeks. Body weight and fecal microbiota structure of the mice were examined at 3-, 5-, 7-, and 9-weeks post gavage. Microbiota richness, beta diversity and discordant taxa were determined using QIIME2 and LEfSe.

The results showed that ~300 ASVswere present in the human feces from human neonates, with higher richness in babies born by CS (181 ASVs) than in VD infants(100 ASVs). Bacteroides dominated the feces of babies born by VD while Citrobacter dominated the feces from babies born by CS.

The neonatal human inocula showed poor engraftment in mice: only 7-17 of the ~300 ASVs in the human fecesengrafted in mice. Contrary to what was expected with the higher richness in the feces of CS born babies, mice transferred the feces from CS born showed lower engraftment (7 ASVs) than mice receiving feces from VD infants (17 ASVs).LEfSe analysis showed that microbiota in mice receiving the VD inoculum was overrepresented by Escherichia-Shigella, Pantoea, Enterococcus, and Bifidobacterium, while Citrobacter koseri was dominant in mice receiving CS inoculum. HFD did not appear to affect the microbiota, though it did result in phenotypic differences with mice consuming HFD gaining more weight. The results suggest that the microbiota of human neonates engrafts poorly into GF mice, and that there are marked differences in engraftment of the feces of neonates by birth mode.

ETD_11348

M.S.

Includes bibliographical references

External ETD graduate

doi:10.7282/t3-st47-9035

The author owns the copyright to this work.