Project Details
Projekt
Elucidate the evolution and function of genes driving Bifidobacterium colonisation in the infant gut
Applicant
Dr. Felix Michael Key
Subject Area
Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 564414949
From birth, the human gut microbiome begins to form, undergoing environmental and compositional changes until it stabilizes within the first few years of life. Bifidobacterium species are among the early pioneers, recognized as keystone species essential for the maturation of a healthy microbiome. Although Bifidobacteria possess a genomic toolkit that allows them to thrive during infancy, the genetic mechanisms driving successful colonization at the strain level remain unclear, despite evidence of their importance. I hypothesize that studying the evolution of Bifidobacteria within infants during the dynamic phase of microbiome formation can uncover unknown genes and genetic variability with adaptive effects crucial for persistent colonization. The major barrier in studying the adaptive, longitudinal progression of commensal microbes during infancy is the lack of longitudinal, viable sample collections. We have enrolled 43 infants and their families, who provide viable stool samples at seven timepoints from birth until the infants' first birthday. Utilizing this unique resource, we will focus on Bifidobacterium longum, a key early member of the human microbiome, collecting over 1,000 isolates and generating their complete genomes to reconstruct population diversity over time. Using whole-genome information, we will first examine the evolution of B. longum within infants during the first year of life to identify genes that promote stable colonization amidst constant environmental changes. We will leverage the family-wide sample collection to determine whether identified adaptive mutations arise de novo within the infant or are seeded from the family. Secondly, using the isolate collection, we will characterize the unknown functions of genes with signatures of natural selection in collaboration with the expert community of the SPP 2474. Specifically, we will conduct in vitro experiments targeting the specific biology of B. longum linked to its characteristic early microbiome colonization to quantify phenotypic differences between mutated and closely-related wild-type isolates. Next, we will measure the effects on interspecies interactions in a controlled experimental setup using a synthetic microbial infant community, developed and provided to us, including training, by SPP 2474 applicants (Bärbel Stecher, Jörg Overmann, and Thomas Clavel [Z01-project]). In summary, this project will significantly enhance our understanding of the genes and their functional impact during adaptation within the developing human microbiome. By focusing on B. longum – an important early colonizer and probiotic – this research holds promise for improving our ability to modulate human microbiome development and promote health.
DFG Programme
Priority Programmes
