Screening competition and cross-feeding interactions during utilization of human milk oligosaccharides by gut microbes

Abstract

Background: The infant gut microbiome is a complex community that influences short- and long-term health. Its assembly and composition are governed by variables such as the feeding type. Breast milk provides infants an important supply of human milk oligosaccharides (HMO), a broad family of carbohydrates comprising neutral, fucosylated, and sialylated molecules. There is a positive association between HMOs and the overrepresentation of Bifidobacterium species in the infant gut, which is sustained by multiple molecular determinants present in the genomes of these species. Infant-gut-associated Bifidobacterium species usually share a similar niche and display similar HMO inclinations, suggesting they compete for these resources. There is also strong evidence of cross-feeding interactions between HMO-derived molecules and bifidobacteria. Methods: In this study, we screened for unidirectional and bidirectional interactions between Bifidobacterium and other species using individual HMO. Bifidobacterium bifidum and Bacteroides thetaiotaomicron increased the growth of several other species when their supernatants were used, probably mediated by the partial degradation of HMO. In contrast, Bifidobacterium longum subsp. infantis. supernatants did not exhibit positive growth. Results: Bifidobacterium species compete for lacto-N-tetraose, which is associated with reduced bidirectional growth. The outcome of these interactions was HMO-dependent, in which the two species could compete for one substrate but cross-feed on another. 2'-fucosyllactose and lacto-N-neotetraose are associated with several positive interactions that generally originate from the partial degradation of these HMOs. Conclusion: This study presents evidence for complex interactions during HMO utilization, which can be cooperative or competitive, depending on the nature of the HMO. This information could be useful for understanding how breast milk supports the growth of some Bifidobacterium species, shaping the ecology of this important microbial community.

Keywords: Bifidobacterium; HMO; cross-feeding interactions; infant gut microbiome.