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Applied and Environmental Microbiology, August 2008, p. 4686-4694, Vol. 74, No. 15
0099-2240/08/$08.00+0     doi:10.1128/AEM.00122-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Differential Transcriptional Response of Bifidobacterium longum to Human Milk, Formula Milk, and Galactooligosaccharide{triangledown} ,{dagger}

Rina González,1,2,{ddagger} Eline S. Klaassens,1,{ddagger}* Erja Malinen,3 Willem M. de Vos,1,3 and Elaine E. Vaughan1,4

Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, The Netherlands,1 Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, Apartado Postal 23-181, México 16000, México,2 Department of Basic Veterinary Sciences, Helsinki University, FI-00014 Helsinki, Finland,3 Unilever Food and Health Research Institute, Unilever Research and Development, Olivier van Noortlaan 120, 3133 AT Vlaardingen, The Netherlands4

Received 15 January 2008/ Accepted 15 May 2008

In order to gain insight into the effects of human breast milk on the development of the intestinal bifidobacteria and associated health effects, the transcriptome of Bifidobacterium longum LMG 13197 grown in breast milk and formula milk containing galactooligosaccharides (GOS) and long-chain fructooligosaccharides was compared to that obtained in a semisynthetic medium with glucose. Total RNA was isolated from exponentially growing cells and hybridized to a clone library-based microarray. Inserts of clones with significant hybridization signals were sequenced and identified. The B. longum transcriptomes obtained during growth on human and formula milk were more similar to each other than to that obtained from growth in semisynthetic medium with glucose. Remarkably, there were only a few genes implicated in carbohydrate metabolism that were similarly upregulated during growth in both human and formula milk although oligosaccharides were added to the formula. Common highly upregulated genes notably included putative genes for cell surface type 2 glycoprotein-binding fimbriae that are implicated in attachment and colonization in the intestine. Genes involved in carbohydrate metabolism formed the dominant group specifically upregulated in breast milk and included putative genes for N-acetylglucosamine degradation and for metabolism of mucin and human milk oligosaccharides via the galactose/lacto-N-biose gene cluster. This supports the notion that the bifidogenic effect of human milk is to a great extent based on its oligosaccharides. The transcriptional effect of semisynthetic medium containing GOS, which, like human milk, contains a large amount of lactose and galactose, on the B. longum transcriptome was also studied and revealed substantial similarity with carbohydrate-utilization genes upregulated during growth in human milk. This knowledge provides leads to optimizing formula milk to better simulate the observed bifidogenic effects of human breast milk.

* Corresponding author. Mailing address: Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, The Netherlands. Phone: 31 317 482105. Fax: 31 317 483829. E-mail: eline.klaassens{at}live.com

{triangledown} Published ahead of print on 6 June 2008.

{dagger} Supplemental material for this article may be found at http://aem.asm.org/.

{ddagger} R.G. and E.S.K. contributed equally to this work.

Applied and Environmental Microbiology, August 2008, p. 4686-4694, Vol. 74, No. 15
0099-2240/08/$08.00+0     doi:10.1128/AEM.00122-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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