Bifidobacterial utilization of human milk oligosaccharides David A. Sela ⁎ Robert Mondavi Institute for Wine and Food Science and Foods for Health Institute, University of California, Davis, CA, USA abstract article info Article history: Received 29 September 2010 Received in revised form 14 January 2011 Accepted 17 January 2011 Available online 26 January 2011 Keywords: Bifidobacterium Milk Oligosaccharides Infant A promising strategy to improve health is the rational manipulation of one's beneficial microbiota via dietary interventions. This is observed in nature where specific bifidobacteria utilize human milk oligosaccharides (HMOs) that are encountered within the breast-fed infant colon. Bifidobacterium longum subsp. infantis is regarded as the archetypical HMO consumer associated with the developing neonate. This review summarizes the known molecular mechanisms underlying HMO utilization, as determined for bifidobacterial commensals. In addition, future directions of HMO research are discussed with an emphasis on physiological, ecological and clinical approaches to understand bifidobacterial utilization of this intriguing substrate. © 2011 Elsevier B.V. All rights reserved. 1. Introduction In the decades following Pasteur, food microbiologists have sought to optimize fermentation and preservation strategies to enhance organoleptic properties and lessen the incidence of spoilage and illness stemming from contaminant microorganisms. Currently, there is resurgent interest in direct ingestion of beneficial microbes and the rational manipulation of one's indigenous microbiota to promote desirable health outcomes, reflecting principles first articulated by Metchnikoff (Metchnikoff, 2004). Believed to mimic natural process- es, a promising approach exploits dietary substrates that are impervious to host metabolism, though they enrich a subset of microorganisms capable of utilizing them, that in turn, benefit their host (Gibson and Roberfroid, 1995). The breast-fed infant gut is an intriguing system to examine the establishment, succession and function of microbiota while limiting the variation of dietary influences to milk's constituents delivered during lactation. From an evolutionary perspective, and often encouraged in modern practice, the neonate receives food from this single source, thus early microbial colonizers of the gastrointestinal tract (GIT) necessarily encounter milk or derived components. Milk incorporates several antimicrobial molecules such as enzymes, peptides and lipids that guide community structure by negatively selecting against certain populations, a property that may permit other bacterial groups to thrive (Phadke et al., 2005; Thormar and Hilmarsson, 2007) [reviewed in (Lawrence and Pane, 2007)]. Whereas pathogen suppression is clearly beneficial to the infant, milk may also encourage beneficial microbes that participate in host metabolism, immune development or other critical physiological processes (Sela and Mills, 2010). Accordingly, there is mounting evidence that milk directly furnishes bacterial cells and/or metabolic products to potentially inoculate or otherwise influence host operations (Martin et al., 2007; Perez et al., 2007). Human milk oligosaccharides (HMOs) do not directly nourish infants, but are thought to enrich for commensal microorganisms capable of utilizing these diverse substrates with most research currently focused on the bifidobacteria (Engfer et al., 2000; Gnoth et al., 2000). In addition to promoting bifidobacterial growth, HMO motifs reflect similar glycan structures found in mucins and epithelial glycoconjugates (Newburg, 2009). Thus HMOs are poised to outcompete preferred host epitopes for ligation by pathogen adhesins within the infant GIT. 2. Early bifidobacterial colonization of the infant Bifidobacteria are anaerobic, saccharolytic, high-GC Gram-positive bacteria that lack motility and do not sporulate or produce gas through typical fermentative metabolism (Sela et al., 2010). This contrasts with heterofermentative lactic acid bacteria that have been historically linked with bifidobacteria due to lactate and acetate production and use in similar industrial applications, despite a disparate phylogenetic origin. A common attribute of bifidobacteria is that they are typically found associated with hosts, primarily as commensals of mammals, although bifidobacterial species are known to colonize certain insect and bird GITs (Turroni et al., 2008). Bifidobacteria have often been reported as overrepresented in breast-fed infants relative to their distribution in adults. This was initially observed in culture-based research, and verified by molecular approaches including a large prospective study as reported by Penders and colleagues (Fallani et al., 2010; Favier et al., 2002; Harmsen et al., 2000; Mariat et al., 2009; Penders et al., 2006; Yoshioka et al., 1983). Yet other studies have characterized infant microbiota with limited International Journal of Food Microbiology 149 (2011) 58–64 ⁎ Tel.: +1 530 754 7962. E-mail address: dasela@ucdavis.edu. 0168-1605/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.ijfoodmicro.2011.01.025 Contents lists available at ScienceDirect International Journal of Food Microbiology journal homepage: www.elsevier.com/locate/ijfoodmicro