Comparative transcriptomics reveals key differences in the response to milk oligosaccharides of infant gut-associated bifidobacteria - PubMed (original) (raw)

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

Daniel Garrido et al. Sci Rep. 2015.

Erratum in

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.

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Conflict of interest statement

Two of the authors (JBG, DAM) are the co-founders of Evolve Biosystems, a company focused on diet-based manipulation of the gut microbiota.

Figures

Figure 1

Figure 1. Representative structure of HMO and major oligosaccharides found in breast milk.

Dashed lines represent glycosidic linkages not found in all HMO.

Figure 2

Figure 2. Principal component analysis (PCA) defined by the two principal components (PC1 and PC2) of the maximum OD600 values of B. infantis (blue) and B. bifidum (red) growth on HMO, LNT, LNnT, 2FL, 3FL, 6SL, mucin and lactose.

Negative control, B. animalis (Yellow). (A) represents variables (oligosaccharides substrates) and (B) bifidobacteria strains.

Figure 3

Figure 3. Whole transcriptome distances in substrate responses of B. infantis (A) and B. bifidum (B).

The heatmap shows the distances between the B. infantis whole transcriptomes in response to the substrate listed: SL6 = 6′siayllactose, FL3 = 3-fucosyllactose, FL2 = 2′fucosyllactose, HMOearly = HMO at early time point, HMOmid = HMO at mid time point, HMOlate = HMO at late time point, LNT = Lacto-_N-_tetraose, LNnT = Lacto-_N-_neotetraose, “(.A)” = first biological replicate, “(.B)” = second biological replicate. The distances calculated are Euclidian distances of the variance-stabilized count data. The darkness of the blue color in the heatmap indicates the degree of similarity, from white (dissimilar) to dark blue (most similar). Likewise, the dendograms also show the distances with larger branch lengths indicating greater distances.

Figure 4

Figure 4. Hierarchical clustering of features (HCF), of the whole transcriptome of B. infantis during growth on HMO and major HMO.

The heat map represents the expression of genes in Table S9.

Figure 5

Figure 5. Hierarchical clustering of features (HCF), of the whole transcriptome of B. bifidum during growth on HMO and major HMO.

The heat map represents the expression of genes in Table S10.

Figure 6

Figure 6. Map of correlations between orthologous transcriptomes in B. infantis and B. bifidum.

Each box in the heatmap represents the correlation between the transcriptomes indicated on the x-axis and y-axis: BLON = B. infantis, BBIF = B. bifidum, SL6 = 6′siayllactose, FL3 = 3′fucosyllactose, FL2 = 2′fucosyllactose, HMOearly = HMO at early time point, HMOmid = HMO at mid time point, HMOlate = HMO at late time point, LNT = Lacto-_N-_tetraose, LNnT = Lacto-_N-_neotetraose “(.A)” = first biological replicate, “(.B)” = second biological replicate. The color key indicates the correlation also indicated by the text in each box: The color key also includes a light blue line that indicates the number of observations at each level of expression.

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