Talare: Hermie J.M. Harmsen, University Medical Center Groningen
Värd: Chinmay Dwibedi, Department of Clinical Microbiologi, MIMS
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The human gut microbiome is increasingly being recognized to play an important role in maintaining health. The bacterial families Lachnospiraceae and Oscillospiraceae in particular, are often reduced in disease states but are relatively poorly represented in culture collections. Cultured representatives are required to investigate the physiology and host interactions of gut microbes.
After establishing a culturomics platform combining a single basal culture medium with MALDI-TOF MS, we built-up a strain bank of more than a thousand gut isolates from healthy and inflammatory bowel disease cohorts. This strain library was used to validate various bioinformatic studies, such as a meta-analysis of associations between human genetic variation and gut microbial structural variation in different population cohorts.
First, strikingly, the presence rate of a structural variation segment in Faecalibacterium strains that harbours an N-acetylgalactosamine (GalNAc) utilization gene cluster is higher in individuals who secrete the type A oligosaccharide antigen terminating in GalNAc, a feature that is jointly determined by human ABO and FUT2 genotypes. In vitro experiments with Faecalibacterium strains demonstrated that GalNAc can be used as the sole carbohydrate source for F. prausnitzii strains that carry the GalNAc-metabolizing pathway. The GalNAc utilization genes are also associated with the host's cardiometabolic health, particularly in individuals with mucosal A-antigen.
Furthermore, structural variation in Anaerostipes hadrus genomes were detected that are linked to the BMI of the individuals. Further validation with strains showed it was related to variation a inositol degradation pathway and propionate production. Additional research on fiber utilization from chicory root showed an enrichment of beneficial bacteria such as the butyrate producing A. hadrus. This shows the potential of such food interventions to improve gut health.
Structural variations in bacterial genomes indicate adaptations of bacteria to both host genetics as well as to the diet of the host and give input to personalized intervention and biotherapeutics for human health.