Colonisation of the infant microbiome
During the first year of an infant's life, the relatively simple infant microbiome matures and develops into a more complex microbiome, with a composition more representative of an adult gastrointestinal tract enriched in Bacteroides and Firmicutes (Backhed et al, 2015). The gut microbiota is a complex and dynamic environment containing 10–100 trillion microorganisms represented by 1000 species involved in numerous biological processes (Ley et al, 2006). They assist in the breakdown of fibre into metabolically and functionally important metabolites, such as short-chain fatty acids (SCFAs) and vitamin K (Lin et al, 2012). They also play a role in immune development and several other areas crucial for our future health (Yoo et al, 2020).
Genetics, mode of birth delivery, infant feeding patterns, antibiotic usage, sanitary living conditions and long-term dietary habits contribute to shaping the composition of the gut microbiome. Emerging evidence suggests that the colonization of microbes in the human body during early life plays a critical role in the establishment and maturation of developmental pathways and that disruption of this optimal microbial succession may contribute to lifelong and intergenerational deficits in growth and development (Charbonneau et al, 2016).
Prebiotics in Human milk
The diet-related factors influencing the development of the infant gut microbiome include whether the child is breast or formula-fed and how and when solid foods are introduced (Voreades et al, 2014). Human milk is the gold standard for the nourishment of early infants because it contains several bioactive components, such as human milk oligosaccharides (HMOs). The high concentration and structural diversity of HMOs are unique to humans. Bifidobacterial species are the main utilisers of HMOs in the gastrointestinal tract and represent the dominant microbiota of breast-fed infants, and they may play an important role in maintaining the general health of newborn children (Musilova et al, 2013). HMOs are thought to play a central role in the development of the neonatal immune system by promoting healthy microbial diversity, preventing pathogen attachment, stimulating the maturation of intestinal epithelial surface and modulation of immune cells (Walsh et al, 2020).
Childhood growth constitutes a prominent and important sign of bodily development, and thus this sensitive health marker is assured by growth control programs worldwide. Human growth comprises four overlapping phases including foetal, infancy, childhood, and pubertal growth. Each growth phase is driven by certain endocrine processes, as well as being influenced by genetic, nutritional, and environmental factors (Murray et al, 2013). Recent investigations suggest that the gut microbiota could be a possible growth regulator too. The first 1000 days – the period from conception to 2 years of age – represent a critical window of early childhood growth and development. Microbes–host interactions may potentially be associated with postnatal growth, although studies showing the causality are limited. The microbiome may play a significant role in limiting human growth, but little is known about changes in the microbiome during periods of undernutrition (Hoffman et al, 2017).
Fibre in children's diets
Fibre is an essential component of the human diet that is crucial for human health. Fibre provides an energy source for the gut microbiome, of which a byproduct is the production of short-chain fatty acids (SCFAs) which stimulate gut motility and have multiple benefits within and beyond the gut including maintaining the effective barrier function of the gut wall and anti-inflammatory properties. SCFAs are known to increase colonic mineral absorption (eg, calcium and magnesium), stimulate the growth of beneficial bacteria (eg, bifidobacteria) in the gut (through cross-feeding) and increase bacterial biomass which can benefit bowel movement (Hojsak et al, 2022).
Impact of antibiotics on microbiomes
Since the discovery of penicillin by Alexander Flemming in 1928 the use of antibiotic agents has transformed medicine and the fight against common life-threatening bacterial infections (Van Boeckel et al., 2014; Tan et al, 2015). Antimicrobial therapy is common practice in paediatric medicine (Blinova et al, 2013). Sadly, sepsis remains the leading cause of mortality in children (Vincent et al, 2009). Widespread antibiotic exposure is associated with the emergence of resistant strains and drug-specific adverse effects, most notably antibiotic-associated diarrhoea (AAD) (Patangia et al, 2022).
Antibiotics disrupt the normal maturation of the microbiome altering basic physiological equilibria and causing dysbiosis (Bhalodi et al, 2019). With 70–80% of immune cells being present in the gut, there is an intricate interplay between the intestinal microbiota, the intestinal epithelial layer, and the local and systemic immune system (Wiertsema et al, 2021). Paradoxically, antibiotic management of sepsis can increase susceptibility to opportunistic and nosocomial infections by affecting the resistance of the intestinal microbiota to colonization (Shah et al, 2021).
A systematic review by McDonnell et al (2020), reports that antibiotic exposure was associated with reduced microbiome diversity and richness, and with changes in bacterial abundance. The potential for dysbiosis in the microbiome should be considered when prescribing antibiotics for children. Of note, antibiotic stewardship programs were developed to limit the inappropriate use of antimicrobial treatment in a bid to reduce the resistance phenomenon and dysbiosis (Klingensmith et al, 2016).
Antibiotic-associated diarrhoea (AAD) is a common complication that occurs in up to one-third of all patients treated with antibiotics. Although almost all oral and intravenous antibiotics can cause AAD, the risk is higher with the use of aminopenicillins (with or without clavulanate), cephalosporins, and clindamycin (Hojsak et al, 2024).
Probiotics in the management of antibiotic-associated diarrhoea
Probiotics are live microorganisms that confer health benefits to the host when administered in adequate amounts. Although recommendations for probiotic use should be strain-specific, many systematic reviews, including recommendations from different societies, recommend probiotic use in general, providing no relevant information for healthcare professionals regarding which probiotic to recommend for which clinical indication, at what dose, and for how long (Hojsak et al, 2024).
Current evidence shows that probiotics effectively prevent and treat AAD in children, and the effect of probiotics on paediatric AAD may be a potential dose-response effect (Yang et al, 2023). A Cochrane review suggests a moderate protective effect of probiotics for preventing AAD. High doses (≥5 billion CFU per day) of S. boulardii or L. rhamnosus GG may be recommended in the management of AAD (Szajewska et al, 2023). However, the benefit of high-dose probiotics needs to be confirmed by a large well-designed multi-centred randomized trial (Guo et al, 2019).
Probiotic Survival
Probiotic microorganisms must survive the hostile acidity of the stomach, bile in the duodenum, and enzymes in the small intestine and colonize the large bowel in sufficient numbers. Furthermore, concerning the number, viability, and functional capacity, which all have to be retained during the entire product shelf-life, beneficial bacteria must survive manufacturing procedures such as repetitive fermentation, cell harvesting, spray, freeze-drying, mixing with an appropriate matrix, storage conditions such as temperature, pH, oxygen exposure and humidity, and type of packaging, to mention just a few examples of the manufacturing determinants that can affect the biological activity of the final product (Grumet et al, 2020). The quality of commercial probiotic products can be unsatisfactory, and more stringent regulatory controls are required, particularly for vulnerable groups such as neonates and children, and when prescribed for defined clinical conditions (Kolaček et al, 2017)
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