Bifidobacterial utilization of human milk oligosaccharides

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Abstract

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.

Research Highlights

► Manipulating beneficial bifidobacteria is a promising strategy to improve health. ► In nature bifidobacteria consume human milk oligosaccharides(HMO). ► These sugars can be used to enhance bifidobacterial populations. ► The future of bifidobacteria and HMO research is discussed as well.

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 processes, 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.

Section snippets

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

Human milk oligosaccharides and the bifidobacteria

HMOs are a heterogeneous mix of soluble glycans that vary by individual and decline over the lactation cycle, but are typically present at ≥ 4 g/L in milk with higher levels observed in colostrum (Asakuma et al., 2008). Structural complexity arises from terminal fucosylation and/or sialylation that impede degradation of HMO core structures (Gyorgy et al., 1974). Despite an immense combinatorial potential, only ~ 200 distinct compositions have been characterized suggesting structure-specific

Current research directions

Pangenomes are the summation of all genes in a designated taxonomic entity and may more accurately describe the distribution of genes in the genus Bifidobacterium, or lower order taxonomies (e.g. Bifidobacterium longum) than single isolated genomes. A pangenome consists of a core set of genes common to a given species or genus as well as variable or dispensable genes that demark those used in niche-adaptation such as those used in HMO processing (Tettelin et al., 2008). Recently, a pangenome

Future research directions

There are three broad themes that arise from research into bifidobacterial consumption of HMO, comprising interdependent approaches including mechanistic studies, microbial ecological interactions and clinical implications (Fig. 3).

Studies of isolated microbes

These lines of inquiry involve physiological studies of culturable bacteria in axenic laboratory cultures or in gnotobiotic models. This represents the natural extension of the research reviewed herein, and employs mechanistic studies of isolated microbes. To accomplish this, there is a tremendous need for a reproducible, and facile, reverse-genetic system to incisively link genomic structure with cellular operations. Previous attempts to develop such a genetic system have failed to yield a

Studies of microbial communities

Microorganisms assemble into multispecies communities in nature prompting the pressing, if not broad, question: how does HMO consuming bifidobacteria interact with host cells/tissue and with other members of the infant microbial consortium? Science is rapidly identifying the profound microbial influence on host matter and energy cycling; therefore it is likely that bifidobacterial HMO consumption is integrated into the community metabolic networks and to that of their host.

To begin answering

Clinical studies at the host-microbial interface

The last future research theme is the most applied, as it concerns microbial interactions with their human host, be it infant or adult. For example, there is much to be learned regarding the consequences to neonatal neural development from bacterial metabolism of milk sialyloligosaccharides as dietary sialic acids are postulated to be integrated in nervous tissue [reviewed in (Wang and Brand-Miller, 2003)].

In order to assess milk's influence, specifically as modulated by microbes, milk's

Concluding remarks

Recent significant advances have been made regarding the molecular mechanisms by which bifidobacteria subsist on HMOs that are unique to their ecological niche within the infant. In hindsight, infant-indigestible milk oligosaccharides are an obvious candidate microbial nutrient as these calorie-dense molecules are delivered to an environment with a high microbial concentration, and reasonably deficient for other carbon sources. Microbial biochemical networks either ensnare HMO or otherwise it

Acknowledgement

D. Mills is thanked for his critical review of the manuscript.

References (68)

  • R. Suzuki et al.

    Structural and thermodynamic analyses of solute-binding protein from Bifidobacterium longum specific for core 1 disaccharide and lacto-N-biose I

    Journal of Biological Chemistry

    (2008)
  • H. Tettelin et al.

    Comparative genomics: the bacterial pan-genome

    Current Opinion in Microbiology

    (2008)
  • H. Thormar et al.

    The role of microbicidal lipids in host defense against pathogens and their potential as therapeutic agents

    Chemistry and Physics of Lipids

    (2007)
  • I. Adlerberth et al.

    Establishment of the gut microbiota in Western infants

    Acta Paediatrica

    (2009)
  • K. Arunachalam et al.

    Enhancement of natural immune function by dietary consumption of Bifidobacterium lactis (HN019)

    European Journal of Clinical Nutrition

    (2000)
  • S. Asakuma et al.

    Variation of major neutral oligosaccharides levels in human colostrum

    European Journal of Clinical Nutrition

    (2008)
  • H. Ashida et al.

    Two distinct alpha-L-fucosidases from Bifidobacterium bifidum are essential for the utilization of fucosylated milk oligosaccharides and glycoconjugates

    Glycobiology

    (2009)
  • R. Barrangou et al.

    Comparison of the complete genome sequences of Bifidobacterium animalis subsp. lactis DSM 10140 and Bl-04

    Journal of Bacteriology

    (2009)
  • W. Beckman et al.

    Response of Pseudomonas cepacia to beta-Lactam antibiotics: utilization of penicillin G as the carbon source

    Journal of Bacteriology

    (1979)
  • B.R. Bochner et al.

    Positive selection for loss of tetracycline resistance

    Journal of Bacteriology

    (1980)
  • F. Bottacini et al.

    Comparative genomics of the genus Bifidobacterium

    Microbiology

    (2010)
  • S.K. Clinton et al.

    Effects of ammonium acetate and sodium cholate on N-Methyl-N′-nitro-N-nitrosoguanidine-induced colon carcinogenesis of rats

    Cancer Research

    (1988)
  • L. Dethlefsen et al.

    The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing

    PLoS Biology

    (2008)
  • M.G. Dominguez-Bello et al.

    Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns

    Proceedings of the National Academy of Sciences

    (2010)
  • H.L. DuPont et al.

    Inoculum size in shigellosis and implications for expected mode of transmission

    The Journal of Infectious Diseases

    (1989)
  • M. Fallani et al.

    Intestinal microbiota of 6-week-old infants across Europe: geographic influence beyond delivery mode, breast-feeding, and antibiotics

    Journal of Pediatric Gastroenterology and Nutrition

    (2010)
  • G. Falony et al.

    Cross-feeding between Bifidobacterium longum BB536 and acetate-converting, butyrate-producing colon bacteria during growth on oligofructose

    Applied and Environmental Microbiology

    (2006)
  • C.F. Favier et al.

    Molecular monitoring of succession of bacterial communities in human neonates

    Applied and Environmental Microbiology

    (2002)
  • M. Gueimonde et al.

    Breast milk: a source of bifidobacteria for infant gut development and maturation?

    Neonatology

    (2007)
  • P. Gyorgy et al.

    Undialyzable growth factors for Lactobacillus bifidus var. pennsylanicus

    European Journal of Biochemistry

    (1974)
  • H.J.M. Harmsen et al.

    Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods

    Journal of Pediatric Gastroenterology and Nutrition

    (2000)
  • J.B. Healy et al.

    Catechol and phenol degradation by a methanogenic population of bacteria

    Applied and Environmental Microbiology

    (1978)
  • T. Katayama et al.

    Molecular cloning and characterization of Bifidobacterium bifidum 1, 2-alpha-L-fucosidase (AfcA), a novel inverting glycosidase (glycoside hydrolase family 95)

    Journal of Bacteriology

    (2004)
  • J.E. Koenig et al.

    Microbes and Health Sackler Colloquium: succession of microbial consortia in the developing infant gut microbiome

    Proceedings of the National Academy of Sciences

    (2010)
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