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Defining the LEGACY of the Maternal Vaginal Microbiome in Microbial Communities of the Infant Gut

Date

2023-05-10

Journal Title

Journal ISSN

Volume Title

Publisher

ORCID

0000-0001-7793-3501

Type

Thesis

Degree Level

Doctoral

Abstract

Over the past decade, small-scale studies have suggested that human colonisation by microbes begins in utero, as evidenced by detection of bacterial DNA in placental tissues and amniotic fluid. Others have suggested that caesarean section (CS) delivery causes dysbiosis in the infant gut microbiome directly due to a lack of exposure to maternal vaginal microbes and that this may be corrected by direct transfer of maternal vaginal microbes These controversial observations in the absence of robust supporting evidence highlight the need to study the acquisition and development of human microbiomes from birth. In this thesis, I have studied the composition and development of the infant stool microbiome immediately following birth, up to three months of life, using a combination of culture-based and culture-independent methods, largely based on cpn60 amplicon sequencing. I demonstrated that the neonatal meconium microbiome is almost entirely comprised of exogenous contaminating DNA, arguing against an in utero colonisation hypothesis and highlighting the need for robust controls in all microbiome studies. I have also shown that the maternal vaginal microbiome composition at delivery does not affect the composition of the infant stool microbiome, and that the effect of birth mode on the latter is confounded by intrapartum antibiotic administration during delivery. Finally, I found that direct transmission of maternal vaginal microbes to the infant gut is generally limited, although still a possibility during vaginal delivery, and highlighted the likely role played by other maternal sources- such as breast milk and stool- in the development of the infant stool microbiome. This work adds to the growing body of evidence showing that the gestational environment is largely sterile until birth and provides much-needed insight into one of the factors long speculated to impact the composition and maturation of the infant stool microbiome. That the maternal vaginal microbiome appears to have little impact on the latter suggests that attempts to correct birth mode-related dysbiosis using vaginal microbes are likely to be of limited efficacy and emphasises the need to focus on other, more influential factors.

Description

Keywords

Vaginal microbiome, gut microbiome, infant microbiome, cpn60, meconium microbiome, microbiome transmission

Citation

Degree

Doctor of Philosophy (Ph.D.)

Department

Western College of Veterinary Medicine

Program

Veterinary Microbiology

Advisor

Citation

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DOI

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