Abstract
Background: The early life period represents the first step in establishing a beneficial microbial ecosystem, which in turn affects both short and longer-term health. Changes during pregnancy influence the neonatal microbiome; through transmission of maternal microbes during childbirth, and beyond, through nutritional programming. However, in-depth exploration of longitudinal maternal-infant cohorts, with sampling of multiple body sites, complemented by clinical and nutritional metadata, and use of cutting-edge experimental systems are limited. The PEARL study will increase our knowledge of; how microbes (including viruses/phages, bacteria, fungi and archaea) change in composition and functional capacity during pregnancy; transmission pathways from mother to infant; the impact of various factors on microbial communities across pregnancy and early life (e.g. diet), and how these microbes interact with other microbes and modulate host processes, including links to disease onset.
Methods: PEARL is a longitudinal observational prospective study of 250 pregnant women and their newborns, with stool and blood samples, questionnaires and routine clinical data collected during pregnancy, labour, birth and up to 24 months post birth. Metagenomic sequencing of samples will be used to define microbiome profiles, and allow for genus, species and strain-level taxonomic identification and corresponding functional analysis. A subset of samples will be analysed for host (immune/metabolite) molecules to identify factors that alter the host gut environment. Culturing will be used to identify new strains of health-promoting bacteria, and potential pathogens. Various in vitro and in vivo experiments will probe underlying mechanisms governing microbe-microbe and microbe-host interactions.
Discussion: Longitudinal studies, like PEARL, are critical if we are to define biomarkers, determine mechanisms underlying microbiome profiles in health and disease, and develop new diet- and microbe-based therapies to be tested in future studies and clinical trials.
Trial registration: This study is registered in the ClinicalTrials.gov Database with ID: NCT03916874.
| Original language | English |
|---|---|
| Article number | 357 |
| Number of pages | 11 |
| Journal | BMC Pediatrics |
| Volume | 21 |
| Issue number | 1 |
| Early online date | 24 Aug 2021 |
| DOIs | |
| Publication status | Published - Dec 2021 |
Bibliographical note
Funding Information:The authors would like to acknowledge the site-specific clinic staff members as well as the mothers and infants for participating in the PEARL study. We would like to thank the NRP Biorepository providing long term storage of samples from the PEARL study and for providing access to the Achiever Medical Laboratory Information Management System for the PEARL study team. We would also like to thank the NNUH Patient Research Ambassadors Ron Brewer, Tony Jackson and Rosalinde Bailey for their involvement in the PEARL study Trial Management Oversight Group and their invaluable contributions and advice regarding participant involvement in this clinical research.
The study has been funded by BBSRC through an Institute Strategic Programme (ISP) award to the QIB Gut Health and Food Safety Programme (BB/R012490/1), and its constituent projects BBS/E/F/000PR10353 and BBS/E/F/000PR10356. The study is into the NIHR CRN Central Portfolio Management System (CPMS, add study number and speciality) portfolio which provides additional support in terms of hospital infrastructure and staff support. George Savva is funded through the BBSRC Core Capability Grant BB/CCG1860/1 at the Quadram Institute Bioscience. The Achiever Medical Laboratory Information Management System was procured using the BBSRC Capital Grant Award for the enhancement of the NRP Biorepository.
Publisher Copyright:
© 2021, The Author(s).
Keywords
- Early-life
- Gut health
- Health
- Microbiome
- Pregnancy
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health