The PEARL-AGE Study. Multigenerational Gut Bacteria Transmission and Its Stability in Families.

Study Overview
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Brief Summary
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We will recruit up to 4-generations of human family cohorts, in order to characterize the microbiome and its changes across different generations.

Detailed Description
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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. We 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 we 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. We 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 co-habiting family members and siblings.

Official Title
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Multigenerational Gut Bacteria Transmission and Its Stability in Families

Conditions
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Microbial Transfers in the Gut of Multigenerational Families and Stability and Adaptation of These Microbes After Colonization

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The following relations of the PEARL mother/baby are eligible for inclusion: Husband/partner of a PEARL mother, their biological parents and grandparents. PEARL mother's biological parents and grandparents (great-grandparents to the PEARL baby). Co-habiting non-biological fathers of the baby such as stepfathers and partners of the PEARL mother, their parents and grandparents. A biological sibling of the PEARL baby or a step-sibling who is currently co-habiting with the PEARL baby. 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: Not related/affiliated to a mother currently participating in the PEARL study, or the cohabiting partner, or father of the PEARL infant. If a PEARL participant has withdrawn from the PEARL study or is no longer participating, we will not approach the PEARL participant for recruitment of their family members. Step-fathers or long-term partners that have been co-habiting with the PEARL mother for less than three months. Those currently in prison. Those who are unable to provide written informed consent. Living with or related to a member of the Research Study team.
Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gut microbiome, microbial adaptation, microbial evolution