Clinical trial NCT05346016: The PEARL-AGE Study. Multigenerational Gut Bacteria Transmission and Its Stability in Families.
Official title: Multigenerational Gut Bacteria Transmission and Its Stability in Families
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Family Research
Keywords: gut microbiome
microbial adaptation
microbial evolution
Lead sponsor: Quadram Institute Bioscience
Sponsor class: OTHER
Collaborators: name: Earlham Institute
name: Norfolk and Norwich University Hospitals NHS Foundation Trust
name: Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK)
First posted: 2022-04-26
Enrollment: 600
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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.

Brief summary: Investigators will recruit up to 4-generations of human family cohorts, in order to characterize the microbiome and its changes across different generations.

Detailed description: 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.

Eligibility criteria: 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, investigators will not approach the PEARL participant for recruitment of their family members.
* Step-fathers or long-term partners that have been cohabiting 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.

Primary outcomes:
measure: Characterizing microbial transfers in multigenerational families and subsequent stability of microbial colonization.
timeFrame: 2026
Secondary outcomes:
measure: Characterizing gut microbial evolution and adaptation in human host families.
timeFrame: 2026
Other outcomes:
measure: Describing the prokaryotic and eukaryotic genome-level diversity within the human gut
timeFrame: 2024
measure: Identify predictors of within-family gut microbe transfer rates
timeFrame: 2026
Locations:
city: Norwich
country: United Kingdom
facility: Quadram Institute Biosciences
state: Norfolk
Study officials:
affiliation: Quadram Institute Bioscience
name: Falk Hildebrand, PhD
role: PRINCIPAL_INVESTIGATOR
References: