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The uncharted sweet side of our microbiota

23.01.2025 12:30 pm 2:00 pm Joint Microbiological Colloquium Rob van Dalen

Spreaker: Rob van Dalen (Amsterdam University Medical Center

Host: Andreas Peschel (CMFI)

Date & Time: 23.01.2025 | 12:30 – 2 p.m.

Venue:  Lecture hall 3M07, GUZ

Public event. No registration needed.

 

Abstract:

The microbiota greatly impacts human health and disease. The host must therefore carefully maintain homeostasis of its microbiota, while defending against pathogens with minimal damage to beneficial commensal species. This raises the question of which microbial properties allow the immune system to make this discrimination and select for a health-promoting microbiota. The bacterial microbiota produces a large variety of glycans, which can be recognized by glycan-recognizing molecules of both the innate and adaptive arms of the immune system. For innate recognition, C-type lectin receptors on antigen-presenting cells are critical as they can sample glycan-bearing bacteria, even across epithelial barriers. In addition, glycan-reactive antibodies of the adaptive immune system have the potential to protect against pathogens as well as promote symbiosis with commensals. Thereby, the total repertoire of bacterial glycans (the ‘glycome’) bears important biological information for the host. Unfortunately, the bacterial glycome still represents a significant blind spot in our understanding of host-microbiota interactions, since we currently lack the tools to study glycans of complex microbial communities in a comprehensive, high-throughput manner.

We have developed glycan-SEQ – a novel method to identify microbiota species with immune-reactive glycan signatures. Glycan-SEQ is based on bacterial cell sorting and subsequent metagenomic sequencing of bacterial microbiota using nature’s own glyco-probes, namely C-type lectin receptors and defined glycan-reactive antibodies. Ongoing work focuses on the application of glycan-SEQ on fecal microbiota samples from healthy donors to characterize how glycan-based immune recognition drives immune selection of microbiota species. Understanding of the molecular mechanisms that drive these immune responses can aid the rational design of strategies that prevent infection while preserving microbiota integrity, for example through microbiota engineering or probiotic vaccination.

 

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