Comparative transcriptomics reveals key differences in the response to milk oligosaccharides of infant gut-associated bifidobacteria.

Daniel Garrido,Santiago Ruiz-Moyano,J Bruce German,David A Mills,David A Sela,Danielle G Lemay

doi:10.1038/srep13517

Abstract

Breast milk enhances the predominance of Bifidobacterium species in the infant gut, probably due to its large concentration of human milk oligosaccharides (HMO). Here we screened infant-gut isolates of Bifidobacterium longum subsp. infantis and Bifidobacterium bifidum using individual HMO, and compared the global transcriptomes of representative isolates on major HMO by RNA-seq. While B. infantis displayed homogeneous HMO-utilization patterns, B. bifidum were more diverse and some strains did not use fucosyllactose (FL) or sialyllactose (SL). Transcriptomes of B. bifidum SC555 and B. infantis ATCC 15697 showed that utilization of pooled HMO is similar to neutral HMO, while transcriptomes for growth on FL were more similar to lactose than HMO in B. bifidum. Genes linked to HMO-utilization were upregulated by neutral HMO and SL, but not by FL in both species. In contrast, FL induced the expression of alternative gene clusters in B. infantis. Results also suggest that B. bifidum SC555 does not utilize fucose or sialic acid from HMO. Surprisingly, expression of orthologous genes differed between both bifidobacteria even when grown on identical substrates. This study highlights two major strategies found in Bifidobacterium species to process HMO, and presents detailed information on the close relationship between HMO and infant-gut bifidobacteria.

Highlights

Than 50 HMO species are normally abundant in an individual mother’s milk[5]
There are only a few bifidobacterial species that are consistently isolated from infant feces, including Bifidobacterium longum subsp. longum (B. longum), Bifidobacterium longum subsp. infantis (B. infantis), Bifidobacterium breve, and Bifidobacterium bifidum, among other lesser taxa[11,15,16,17]
It has been previously shown that certain infant-associated bifidobacteria can utilize HMO purified from breast milk as the sole carbon source[18]

Summary

Introduction

Than 50 HMO species are normally abundant in an individual mother’s milk[5]. Major HMO secreted in milk include lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT) and lacto-N-hexaose, which are neutral HMO, in addition to fucosylated molecules such as 2- fucosyllactose (2 FL), 3-fucosyllactose (3FL), and lacto-N-fucopentaoses I, II and III5. Studies have consistently shown that the composition of the intestinal microbiome among breast-fed and formula-fed infants is different[9,10,11] This is consistent with HMO enriching for the populations capable of efficiently utilizing these substrates. It has been previously shown that certain infant-associated bifidobacteria can utilize HMO purified from breast milk as the sole carbon source[18] This first suggested potential co-evolution between bifidobacteria and their mammalian hosts mediated by milk oligosaccharides. This consumption phenotype was observed for some B. infantis and B. bifidum strains[19,20], and recently it has been shown that several B. breve can target these molecules, including fucosylated HMO21

Methods

Results

Discussion

Conclusion