PhD Graduate

Michael Jakob Pichler's PhD Defence

Michael Jakob Pichler defends his PhD thesis Exploring the Molecular Basis of Glycan Utilization be Health Relevant Members of the Human Gut Microbiota.

Supervisor
Professor MSO Maher Abour Hachem, DTU Bioengineering

Examiners

  • Professor Peter Westh, DTU Bioengineering 
  • Professor Karsten Kristiansen, University of Copenhagen
  • Professor Bernd Nidetzky, Graz University of Technology, Austria

Chair at the defence
Professor Birte Svensson, DTU Bioengineering

Abstract
The microbial community that colonizes the human gut, known as the human gut microbiota (HGM), has a profound impact on human health. Perturbations of the assembly of the HGM during infancy are associated with the later onset of serious inflammatory and metabolic disorders including type 1 diabetes, asthma, inflammatory bowel disease or obesity, underscoring the critical role of the early HGM for human health. Strikingly, our understanding of factors driving the early HGM development towards health-associated signatures remains limited. A conspicuous gap of our knowledge involves the mechanisms that define the transition of the gut microbiota from a mothers milk based diet to solid food during weaning. The weaning phase involves dramatic shifts in the microbiota composition, and the factors underpinning these transitions, as well as the emergence of specific taxonomic groups associated with a healthy adult microbiota remain unclear. An example of this is the establishment of the Roseburia-Eubacterium Firmicutes group, which are associated with the protection from colorectal cancer, immune- and metabolic disorders. Members of this group are early colonizers of the developing infant gut and they are abundant and prevalent members of the adult gut microbiota, but their life style during early life has not been investigated.

In this thesis, we reveal catabolic pathways that confers the growth of Roseburia-Eubacterium group members on specific human milk oligosaccharides (HMOs). We have performed growth, genomic, proteomic, structural, biochemical and biophysical analyses to elucidate and characterize the molecular basis of growth on HMOs.

We also show that the HMOs pathways and additional glycan utilization loci confer co-growth with the primary mucin degrader Akkermansia muciniphilia via direct access and cross-feeding on mucin O-glycans. Our findings highlight the HMOs utilization capabilities of Roseburia-Eubacterium, which provides a possible mechanism for their early establishment and resilience in the human gut. Moreover, the ability to access mucin derived O-glycans via cross-feeding using the HMOs catabolic apparatus, may confer resilience to this taxonomic group during periods of dietary glycan restriction. These findings offer the first insight into a new role of HMOs in modulating health relevant butyrate producing members of the Roseburia-Eubacterium group. This knowledge provides the foundation for the design of future milk formula and glycan based interventions targeting butyrate producing Clostridiales form the healthy human gut.

All are welcome. Registration is not necessary.

Copy of the PhD thesis is available at the department reception.

Time

Mon 24 Feb 20
12:15 - 17:00

Organizer

DTU Bioengineering

Where

Building 101, Room S10