Mucin Cross-feeding Shapes The Metabolic Environment In The Infant Gut

Mucin is released by mucous and goblet cells of the gastrointestinal tract. Production starts before birth, and a complete mucus layer has already developed shortly after birth. Human mucins are glycoproteins composed of a polypeptide backbone and glycosylated side chains. Mucin thus provides a nutrient-rich, reliably present carbon and nitrogen source for gut microbes already at an infant age. However, only a few bacterial species can efficiently degrade mucus, and mucin degraders are rare among the infant gut microbiota.

Mucus utilization might have further ecological implications as it has been suggested that the presence of mucin degrading specialists may play a pivotal role in early infant colonization providing nutrients to other gut microbes before dietary fibers are introduced during weaning. These nutrients would include mono- and disaccharides released from the mucin polymers, fermentation intermediates (for example lactate, 1,2-propanediol, a precursor for propionate), and metabolites such as short-chain fatty acids (acetate, propionate, and butyrate), which can be also used by specialized microbes.

Bifidobacteria are the major bacterial group in feces of vaginally delivered and breast milk-fed infants. Among the bifidobacteria, Bifidobacterium bifidum is the only species that can degrade and grow in the presence of mucin. Mucin monosaccharides released by B. bifidum can be used by other gut microbes. We hypothesized that mucin cross-feeding of B. bifidum and infant gut microbes that cannot use mucin might leads to short-chain fatty acid formation. This creates an environment that would support the colonization of gut microbes that demand the presence of short chain fatty acids to grow. Whereas several studies have been investigating the composition of the infant gut microbiota, much less is known about metabolic networks at this age.

We, therefore, investigated growth, mucin-degradation and metabolite formation of B. bifidum in co-culture with the non- mucin utilizing Bifidobacterium breve, Bifidobacterium longum subsp. infantis and the early colonizing butyrate, and propionate producing Eubacterium hallii. In co-culture fermentations, B. bifidum enabled growth of the other species. B. breve or B. longum subsp. infantis used mucin-derived hexoses, and fucose to form acetate, lactate, and 1,2-propanediol, respectively while E. hallii produced butyrate from lactate and acetate or glucose. In three strain-co-cultures of B. bifidum, B. longum subsp. infantis or B. breve, and E. hallii, acetate, butyrate, and propionate were produced, latter indicated Bifidobacterium/E.hallii cross-feeding on fucose, one sugar component that is mainly produced by mammalian cells.

In summary, we demonstrate that mucin degradation by B. bifidum enabled growth of the metabolic versatile E. hallii. Trophic interactions of bifidobacteria and E. hallii led to the production of acetate, butyrate, propionate, and formate. This formation potentially contributes to intestinal short chain fatty acid formation with potential benefits for the host and for infant gut microbial colonization. Bifidobacterium – E. hallii mucin cross-feeding might improve environmental conditions for (adult) butyrate producing microbes such as Faecalibacterium, Coprococcus, and Roseburia, which depend on the presence of short chain fatty acids for growth.

These findings are described in the article entitled Mucin Cross-Feeding of Infant Bifidobacteria and Eubacterium hallii, published in the journal Microbial Ecology. This work was led by Vera Bunesova, Christophe Lacroix, and Clarissa Schwab from ETH Zürich and the Czech University of Life Sciences Prague.