Microbial colonization in our gut starts from birth and followed by the dynamic succession of different microbial groups early in life. This happens concurrent with the development of immune, metabolic and neurological system that may impact lifelong health. Microbes colonising the infant gut mucosa are particularly critical to prime mucosal immune response and tolerance. At this period, infant nutrition plays a crucial role in steering the establishment of the gut microbiota.
Human host-secreted glycans such as HMOS and mucins are important drivers for the composition and functionality of the gut microbiota. Due to the complex chemical nature of milk and mucin glycans, only some gut bacteria with refined capability are able to utilise it as growth substrates. These glycan-degrading bacteria subsequently drive the microbial network via cross-feeding. In essence, the glycan-degrading bacteria produce metabolic products or nutrients to sustain the growth and metabolism of the bacterial community in the vicinity. The resulting glycan-enriched subpopulation could influence the physiological development of infants and confer colonisation resistance throughout life.
This thesis unravels the interaction of gut symbionts in the presence of HMOS or host-derived mucins. More specifically, Loo Wee investigated the interaction between two groups of bacteria that are predicted to cross-feed i.e. glycan-degraders (including bifidobacteria and Akkermansia muciniphila) and butyrate-producing Clostridia, which have been implicated to be important in priming the development of immune system.
The ability of the glycan-degraders to support the growth and activity of butyrate-producing Clostridia is clearly demonstrated in this thesis. Cross-feeding between these two bacterial groups leads to the production of butyrate from the breakdown of glycan structures. Butyrate is shown to be important for gut integrity and gut health. Gut maturation early in life is an important driver of overall healthy development. The initial HMOS-degrading bacteria provide substrates and create the environment for other important species that will colonise the infant gut after weaning. The gradual increase of the butyrate and the emergence of butyrogenic community in the gut is important for gut maturation, and delayed production could potentially be associated with colicky symptoms and atopic diseases in infants.
This thesis provides insights for the design of novel nutritional approaches to modulate the gut microbiota. These include novel probiotic strains that are not used traditionally. Furthermore, the potential of supplementing infant nutrition with novel microbial substrates is highlighted to further close the compositional gap between human milk and infant formula.
Loo Wee’s promotor is Prof. Dr Jan Knol, Special Professor intestinal microbiology of early Life, Wageningen University & Research and Research Director Gut Biology & Microbiology, Danone Nutricia Research, The Netherlands. Co-promotor is Dr Clara Belzer, Assistant professor, Laboratory of Microbiology, Wageningen University & Research. This research project works in close collaboration with the Human Milk Research team, Danone Nutricia Research lead by Dr Bernd Stahl.