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| Name | Class |
|---|---|
| Earlham Institute | UNKNOWN |
| Norfolk and Norwich University Hospitals NHS Foundation Trust | OTHER |
| Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK) | OTHER |
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Investigators will recruit up to 4-generations of human family cohorts, in order to characterize the microbiome and its changes across different generations.
Interest in the gut microbiome from both the scientific community and public has increased exponentially over the last decade. Yet our knowledge of the microbes in the gut microbiome, their persistence and dispersal to new human hosts is still surprisingly ill-defined.
Investigators hypothesize that some gut microbes persist over multiple generations and are adapted to varying degrees to their human hosts and families, making them potentially important members of the human gut. Bacterial strains can persist in the human host for years, with maternally-transferred strains known to persist longer in infants than environmentally acquired ones. It is conceivable that a given strain can colonize a host for several vertical generations, as already shown for Bifidobacterium using cultured isolates. Yet investigators currently lack knowledge of microbial persistence over multiple generations, and the proposed PEARL-AGE cohort is the first study investigating multi-generation persistence of gut bacteria (to our best knowledge).
The PEARL-AGE project will investigate microbial transfer and the evolution of microbes in family members from different generations. Investigators will recruit siblings, fathers/guardians, grandparents, and great-grandparents to fully capture vertical (between generations) and horizontal (same generation) microbial transmission across multiple generations, as well as tracking parallel microbial evolution in multiple family members. This will substantially increase our understanding of microbial transmission, long-term microbial persistence through generations and between cohabiting family members and siblings.
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| Measure | Description | Time Frame |
|---|---|---|
| Characterizing microbial transfers in multigenerational families and subsequent stability of microbial colonization. | High-resolution metagenomics of strains tracked over time in individuals and families, relative to collected metadata (family closeness, medical history, etc) Associating microbiome stability to human genetic loci. | 2026 |
| Measure | Description | Time Frame |
|---|---|---|
| Characterizing gut microbial evolution and adaptation in human host families. | Comparative genomics of metagenome assembled genomes (MAGs) per individual. Identifying newly introduced mutations in microbial genomes. Observing parallel evolution (e.g., loss or gain of the same genes in bacteria). Associating human genotypes to microbial adaptation. | 2026 |
| Measure | Description | Time Frame |
|---|---|---|
| Describing the prokaryotic and eukaryotic genome-level diversity within the human gut | Newly developed DNA extraction protocols for enrichment of specific microbial clades. | 2024 |
| Identify predictors of within-family gut microbe transfer rates |
Inclusion Criteria:
The following relations of the PEARL mother/baby are eligible for inclusion:
Adult participants must be able to consent for themselves and able to understand the questionnaire.
Child participants must have a parent and/or guardian to provide assent on their behalf.
Must be living in England.
Must be willing to accommodate a small cool box to store and transport the biological samples until they are collected, if not having immediate access to the PEARL study freezer.
Vulnerable participants such as participants with mild cognitive impairment may be included as long as they have full support from their family members.
Exclusion Criteria:
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Investigators are recruiting the family members of PEARL (ClinicalTrials.gov ID: NCT03916874) study participants, a longitudinal study to understand how gut microbes contribute to maintaining health during pregnancy and early life already underway at QIB (Quadram Institute Bioscience). Investigators will extend this cohort, by recruiting family members of the PEARL mother to form the PEARL-AGE cohort, extending it from two generations to four generations.
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| Name | Affiliation | Role |
|---|---|---|
| Falk Hildebrand, PhD | Quadram Institute Bioscience | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Quadram Institute Biosciences | Norwich | Norfolk | NR4 7UQ | United Kingdom |
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Faecal samples will be collected from the participants.
Correlation coefficient of collected metadata (questionnaire derived) to observed shared microbes Correlate parallel colonization's of sibling to family questionnaire metadata (e.g. distances, closeness, habits, ..) Correlate genetic factors (immune system, etc) to microbial sharing/colonization rates
| 2026 |