Programming infant gut microbiota: influence of dietary and environmental factors

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The neonatal period is crucial for intestinal colonisation, and the composition of this ecosystem in early life is influenced by such factors as mode of birth, environment, diet and antibiotics. The intestinal microbiota contributes to protection against pathogens, maturation of the immune system and metabolic welfare of the host, but under some circumstances can contribute to the pathogenesis of certain diseases. Because colonisation with non-pathogenic microbiota is important for infant health and may affect health in later life, it is important to understand how the composition of this microbial organ is established and by which dietary means (e.g. supplementation with prebiotics/probiotics/food ingredients) it can be programmed in order to achieve an ecosystem that is valuable for the host.

Introduction

Microbial colonisation of the sterile infant intestine is an intricate process which is influenced by many factors [1] including mode of delivery [2], type of feeding [3] and antibiotic therapy [4, 5]. Within the first year of life, the enteric microflora is highly dynamic but microbial diversity is low, and after the initial year, the microbial population stabilises and resembles that of the adult [6]. Whilst traditional culture-based techniques have been used in the past to determine the microbial load of the infant intestine, less biased DNA-based techniques including the use of the 16s ribosomal RNA gene have recently confirmed the dominance of species of Bifidobacterium, Clostridium and Bacteroides in the early microbiota [7, 8, 9, 10]. However, using sequencing techniques Wang et al. [7] found that 10% of species from faecal samples of infants after the first two months of life were unidentifiable, whereas 30% unidentified species were observed after the first year of life, highlighting the complexity of the microbiota and the importance of the development of new and more powerful fingerprinting techniques. In a more recent study by Rajilić-Stojanović et al. [11], a phylogenetic microarray (referred to as the human intestinal tract chip or ‘HITChip’) was developed and applied for comparing the effect of ageing on the intestinal microbiota of young and elderly adults. Because of the good reproducibility and the possibility for relative quantification of microbial groups, this technique might be a suitable tool for determining the microbial diversity of the infant gastrointestinal tract in future studies. Another high-throughput alternative test is the recently launched GA-map™ microarray that will enable screening of the infant gut microbiota based on sets of unique probes that are highly specific to their target group of bacteria. It is envisaged that by providing an ‘overall map’ of the enteric microbiota, this test will give valuable information to assist in disease intervention [12].

The mutualistic interactions between the enteric microbiota and the human host are essential for health [13]. Indeed, the enteric microbiota can secrete molecules (so-called ‘pharmabiotics’ [14]) that inhibit host pathogens, metabolise compounds that harm the host to less toxic substances [13, 15] and produce a range of bioactive compounds such as conjugated linoleic acid (CLA), short chain fatty acids (SCFA) and gamma-aminobutyric acid (GABA) that may play a role in the protection from lifestyle illnesses such as cancer, obesity and cardiovascular diseases [15]. Moreover, the microbiota contribute to biochemical pathways that humans cannot process because of the lack of proper genes [16], such as fermentation of indigestible dietary polysaccharides, metabolism of complex proteins and synthesis of vitamins [15, 17]. The infant gut microbiota can also significantly influence the maturation of the immune system in early days of life [14, 18, 19]. Remarkably, colonisation of the newborn intestine plays a key role in the development and fine-tuning of the intestinal immune responses. Disruption to this process, due for example to antibiotic therapy, may have long-term health consequences, giving rise to immune-related disorders such as eczema, allergic rhinitis and inflammatory bowel disease (IBD) [18, 20]. For example, in a study conducted by Wang et al., the intestinal microbial diversity of 18-month-old infants suffering from atopic eczema was reduced in comparison to healthy infants of the same age [21].

As the infant enteric microbiota is more variable in its composition and less stable over time compared to the adult [6], the use of nutritional strategies in order to shape/programme its composition to favour a more beneficial bacterial population may be a good opportunity to avoid future health problems. Probiotics and prebiotics are widely used as supplements in infant formulae and many studies have confirmed their efficacy in changing the microbiota composition by stimulating the growth of bifidobacteria [22] and therefore helping in the treatment and prevention of certain illnesses [23, 24].

This review will discuss the current knowledge of the microbial diversity in infants and the metabolic capabilities that the enteric microbiota possess. Furthermore, the impact of diet and dietary supplementation (with probiotics and prebiotics) on the evolution of the microbial diversity in the developing infant will be reviewed.

Section snippets

Development of the infant gut microbiota

At birth, the newborn infant gastrointestinal tract is almost sterile [25, 26, 27], but is rapidly colonised in the first days of life, reaching a stable population similar to that of an adult when the infant is around two years old and there is the introduction of solid foods [6, 13, 15, 28]. Immediately after birth, the newborn gut environment is colonised by facultative anaerobic bacteria such as Enterobacteriaceae, streptococci and staphylococci [10, 29, 30]. These first colonisers belong

Implications of microbiota for host health

The enteric microbiota play an important role in host health, being involved in nutritional, immunological and physiological functions. Along the epithelium, enteric bacteria complement the natural defence barrier against exogenous microbes, thereby preventing invasion by pathogens. In addition, the enteric microbiota have an important role in influencing the normal structural and functional development of the mucosal immune system [37]. The molecular interactions between enteric bacteria and

Metabolite production by gut bacteria

The human enteric microbiota can exert beneficial health effects through the production of bacterial metabolites or ‘pharmabiotics’, most often small molecules which interact with ‘intelligent communication’ systems in the body including those which are immune, endocrine and neuronal-based [14]. Commensal bacteria have been shown to synthesise vitamins that are essential for human survival such as vitamins K2 and B12 [17], polyunsaturated fatty acids (PUFA) such as conjugated α-linolenic acid

Diet and the enteric microbiota

Diet can influence the composition of the intestinal microbiota, especially in the first days of life when the bacterial population is not yet established [23]. The infant microbiota is naturally shaped during breast-feeding but the colonisation pattern can also be manipulated towards a more beneficial community using dietary supplementation with probiotics and/or prebiotics.

Human breast milk is considered the best nutritional option for growth and health development of newborn infants, since

Probiotics and prebiotics

Probiotics are defined as ‘live microorganisms’ which, when administered in adequate amounts confer a health benefit on the host’ [75]. The most common groups of bacteria used as probiotics are bifidobacteria and lactobacilli [23]. Multiple mechanisms of probiotic action have been suggested, however mechanisms are strain-dependent [22]. Probiotics may prevent the penetration of pathogens in the human gut by increasing the production of mucin, reducing the gut permeability, releasing

Conclusions

Early colonisation of the infant gut is undoubtedly an important factor for the overall health of the infant and may also have effects on the health status in later life. Indeed, the commensal microbiota have been implicated in many diseases that occur within the gastrointestinal tract and more recently have also been shown to be involved in disorders outside the gut such as obesity, diabetes and atopic allergies. Several factors have been shown to promote a greater microbial diversity in

Acknowledgements

This work was supported in part, by Science Foundation Ireland, The European Union (Project KBBE-211911), the Irish Ministry for Food and Agriculture, Enterprise Ireland, the Higher Education Authority and the Health Research Board of Ireland and the Irish Government under the National Development Plan 2000–2006. TMM is a student funded by the Alimentary Pharmabiotic Centre (APC).

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