Programming infant gut microbiota: influence of dietary and environmental factors
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).
References (78)
- et al.
Gut microbiota: changes throughout the lifespan from infancy to elderly
Int Dairy J
(2010) - et al.
Impact of ampicillin and cefuroxime on bacterial colonisation and infection in patients on a neonatal intensive care unit
J Hosp Infect
(1993) - et al.
T-RFLP combined with principal component analysis and 16S rRNA gene sequencing: an effective strategy for comparison of fecal microbiota in infants of different ages
J Microbiol Method
(2004) - et al.
Characterisation of intestinal bacteria in infant stools using real-time PCR and northern hybridisation analyses
FEMS Microbiol Ecol
(2005) - et al.
Culture-independent analysis of fecal microbiota in infants, with special reference to Bifidobacterium species
FEMS Microbiol Lett
(2005) - et al.
Importance of microbial colonization of the gut in early life to the development of immunity
Mutat Res
(2007) - et al.
Reduced diversity in the early fecal microbiota of infants with atopic eczema
J Allergy Clin Immunol
(2008) - et al.
Mechanisms of probiosis and prebiosis: considerations for enhanced functional foods
Curr Opin Biotechnol
(2009) - et al.
Is meconium from healthy newborns actually sterile?
Res Microbiol
(2008) Postnatal development of intestinal microflora as influenced by infant nutrition
J Nutr
(2008)
Cesarean delivery may affect the early biodiversity of intestinal bacteria
J Nutr
Probiotics: role in pathophysiology and prevention in necrotizing enterocolitis
Semin Perinatol
Structural and functional aspects of prebiotics used in infant nutrition
J Nutr
An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system
Cell
Early differences in fecal microbiota composition in children may predict overweight
Am J Clin Nutr
Metabolic activity of the enteric microbiota influences the fatty acid composition of murine and porcine liver and adipose tissues
Am J Clin Nutr
Gut microbiota affects lens and retinal lipid composition
Exp Eye Res
The gut microbiota and disease — an inner repository for drug discovery
Drug Discov Today: Ther Strat
Clinical evaluation of a new starter formula for infants containing live Bifidobacterium longum BL999 and prebiotics
Nutrition
Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7
Blood
Quantitative measurement of tetrahydromenaquinone-9 in cheese fermented by propionibacteria
J Dairy Sci
Vitamin K2 suppresses malignancy of HuH7 hepatoma cells via inhibition of connexin 43
Cancer Lett
Folate and cobalamin status in relation to breastfeeding and weaning in healthy infants
Am J Clin Nutr
Specific metabolite production by gut microbiota as a basis for probiotic function
Int Dairy J
Biological effects of conjugated linoleic acids in health and disease
J Nutr Biochem
Production of yogurt with enhanced levels of gamma-aminobutyric acid and valuable nutrients using lactic acid bacteria and germinated soybean extract
Bioresour Technol
Dietary nucleotides and fecal microbiota in formula-fed infants: a randomized controlled trial
Am J Clin Nutr
Breast-feeding and its role in early development of the immune system in infants: consequences for health later in life
J Nutr
Probiotics for prevention of necrotising enterocolitis in preterm neonates with very low birthweight: a systematic review of randomised controlled trials
Lancet
Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after caesarean delivery
J Pediatr Gastroenterol Nutr
Factors controlling the bacterial colonization of the intestine in breast-fed infants
Acta Pediatr
Effect of ampicillin versus cefuroxime on the emergence of beta-lactam resistance in fecal Enterobacter cloacae isolates from neonates
J Antimicrob Chemother
Development of the human infant intestinal microbiota
PLoS Biol
Factors influencing the composition of the intestinal microbiota in early infancy
Pediatrics
Development and application of the human intestinal tract chip, a phylogenetic microarray: analysis of universally conserved phylotypes in the abundant microbiota of young and elderly adults
Environ Microbiol
New infant gut microbiota screening test provides key tool for disease development investigation
Medial News Today
An ecological and evolutionary perspective on human–microbe mutualism and disease
Nature
Pharmabiotics: Bioactives from Mining Host–Microbe–Dietary Interactions
Funct Food Rev
Role of gut microbiota in early infant development
Clin Med: Pediatr
Cited by (242)
Role of gut microbiota in depression: Understanding molecular pathways, recent research, and future direction
2023, Behavioural Brain ResearchGut dysbiosis, defective autophagy and altered immune responses in neurodegenerative diseases: Tales of a vicious cycle
2022, Pharmacology and TherapeuticsGut microbiota interacts with inflammatory responses in acute pancreatitis
2023, Therapeutic Advances in Gastroenterology