Gut microbiota and its role in human health

Gut microbiota account for the microbial community consisting of at least 1014 micro-organisms including predominantly bacteria, but also viruses, archaeans and protozoa. Not surprisingly, microbiota have a significant role in maintaining human health over a lifetime.1
In general, adult gut microbiota are primarily dominated (80%) by three phyla - Bacteroidetes, Firmicutes and Actinobacteria.2 Nevertheless, it must be mentioned that microbiota composition can change over a lifetime and can be influenced by other factors, such as genetics, diet, use of dietary supplements (eg. probiotics, prebiotics) and medications (eg. antibiotics, anti-inflammatory drugs), infections and stressful situations. For example, initial composition of microbiota at birth undergo rapid changes as a result of early exposure to a set of bacteria including staphylococci, enterobacteria and enterococci that immediately colonise the gastrointestinal tract. However, over time, the proportion of those micro-organisms changes rapidly and around the age of one to five months, mainly consists of Bifidobacteriales, Lactobacillales and Clostridiales. Finally, at one year of age, they are similar to the adult microbiota.1

Factors influencing gut microbiota composition in early life

Gut microbiota are established in early pregnancy and vary depending on maternal nutritional habits, infections and gestational age. Furthermore, the delivery mode as well as breastfeeding or formula feeding strongly influences the abundance and diversity of infant microbiota, which modulates the immune system response.3
Type of delivery: The gut of infants born vaginally is colonised prevalently with Bifidobacterium and Streptococcus. In contrast, Caesarean delivery is associated with a decrease of Bifidobacteria, while Clostridium and Bacteroides prevail, as well as lower diversity.3
Use of antibiotics: Antibiotic treatment during pregnancy as part of intrapartum antimicrobial prophylaxis to prevent bacterial infection may further alter the acquisition of neonatal flora promoting preterm delivery,4 as well increase abundance of Enterobacteriaceae in infants.5
Gestational age: Premature infants delivered before 28 gestational weeks, when compared to full-term infants, seem to have a lower bacterial diversity than to babies born at 28 to 32 or 32 to 37 gestational weeks. In preterm infants, the proportion of Bifidobacterium, Bacteroides and Streptococcus decrease, while abundance of Enterobacteriaceae,6 Klebsiella7 or Escherichia coli8 increase, which has been associated with a higher risk of necrotising enterocolitis6 compared to term births.
Breastfeeding: Breastfed infants have been shown to have a lower risk of infections, diarrhoea, type 1 diabetes and necrotising enterocolitis after birth. Breastfeeding is also associated with a reduced risk of chronic conditions, including type 2 diabetes, inflammatory bowel disease and obesity.9

Probiotic supplementation in pregnancy and infancy for early life care - what the research says

Probiotic supplementation during pregnancy may help to reduce infection risk and prevent pre-term delivery. Alteration in the composition of vaginal microbiota during pregnancy, characterised by colonisation of group B Streptococcal (GBS), has been shown to increase risk of preterm delivery and could contribute to neonatal infections, sepsis and necrotising enterocolitis.10 The use of probiotics seems to modulate the composition of vaginal microflora.
A pilot prospective study demonstrated that dietary supplementation with a mixture containing L paracasei DSM 24733, L plantarum DSM 24730, L acidophilus DSM 24735 and L delbrueckii subsp. bulgaricus DSM 24734, three strains of bifidobacteria (B longum DSM 24736, B breve DSM 24732 and B infantis DSM 24737) and one strain of Streptococcus thermophilus DSM 24731, by increasing bifidobacteria and reducing Atopobium vaginae, can effectively prevent bacterial vaginosis.11 Similarly, an oral administration of Lactobacillus reuteri RC-14 and Lactobacillus rhamnosus GR-1 in pregnant women with vaginal and rectal GBS colonisation significantly reduced these colonisation rates in women who received probiotics compared to the placebo group.12
Interestingly, a prospective cohort study has shown that the administration of milk supplemented with probiotics during pregnancy reduced pre-eclampsia and preterm delivery risk.13 An early supplementation of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 in women during gestation also reduced premature delivery risk.14 Although results obtained from these trials suggest that probiotics may prevent preterm births, a 2018 meta-analysis failed to show evidence that administration of probiotics in pregnancy can reduce the risk of preterm delivery.15

Probiotic supplementation potential to prevent food allergies

Food allergies have become a common problem, affecting approximately 6% of infants under two and 9% of children aged from three to five.16 Eggs, milk and peanuts are the most common food allergens and skin problems (eg. eczema) are closely associated with food allergies.17
To date, available evidence has demonstrated that sensitisation against the most common food allergens, such as egg whites, cow’s milk, wheat, peanuts, soybeans and buckwheat appeared to be lower in individuals who received probiotics (38.7%) than in the placebo group (51.7%).18 Also, use of a single strain probiotic containing Lactobacillus reuteri ATCC 55730 in the prenatal and postnatal period significantly decreased levels of circulating IgE to egg white at two years of age in infants at high risk of allergy. However, no effects were observed on other food allergens, such as cow’s milk, cod, wheat, peanuts, and soybeans. Interestingly, the positive effect of the treatment was more pronounced in infants whose mothers, but not fathers, have allergic disease.19

Probiotic supplementation and infantile colic

Probiotics can play an important role in maintaining gut health and may have potential to reduce symptoms of infantile colic, which affects around 20% of babies before four months of age.20 Although infantile colic has a multifactorial aetiology, certain food allergies, as well as gut dysbiosis, have been suggested as risk factors.21 Supplementation of a probiotic mixture containing L paracasei DSM 24733, L plantarum DSM 24730, L acidophilus DSM 24735 and L delbrueckii subsp bulgaricus DSM 24734; three strains of bifidobacteria (B longum DSM 24736, B breve DSM 24732, and B infantis DSM 24737), and one strain of Streptococcus thermophilus DSM 24731, reduced inconsolable crying in exclusively breastfed infants with infantile colic.22
Furthermore, supplementation of Lactobacillus reuteri DSM 17938 with a dose of 108 colony forming units a day from 21 to 28 days was not only effective in reducing the duration of crying episodes during the day,23 but decreased probability of colic and other functional gastrointestinal disorders such as gastro-oesophageal reflux and constipation among breastfed infants.24
Probiotic supplementation before two years of age is effective in preventing eczema and atopic sensitisation
Allergic diseases such as asthma, atopic dermatitis (AD) and allergic rhinoconjunctivitis (ARC) are the main health problems in children, with a prevalence ranging from 9.5% in asthma up to 10-20% in allergic dermatitis.25 Probiotic supplementation during the first six months of life, while not exceeding two years of age, have been shown to significantly decrease the risk of eczema. However, administering a mixture of probiotics, in particular containing both Lactobacilli and Bifidobacteria, has no significant effect in terms of preventing asthma or rhinoconjunctivitis.26
Interestingly, an early childhood supplementation with Lactobacillus rhamnosus HN001 from 35-week gestation to six months’ postpartum in mothers while breastfeeding, as well as from birth to age two years in infants, significantly protected against eczema development at two, four, six years and 11 years. For lifetime prevalence, HN001 was associated with a significant reduction in atopic sensitisation, eczema and wheeze.27

Future directions: use of paraprobiotics in neonatal care 

Preterm babies are often affected by delayed bacterial colonisation, especially by Bifidobacterium and Lactobacillus, which could increase the risk of gut microbiota dysbiosis and settlement of pathogenic bacteria. In addition, delayed introduction of human milk and breastfeeding, similar to early antibiotic intervention,28 could further contribute to disturbances of gut microbiota composition, leading to delayed development of immune function and uncontrolled inflammatory reactions. This can significantly compromise immune responses against pathogens.
Consequently, early introduction of probiotic supplementation appears to be a promising strategy that may support immune defences. Enhancing mucosal immunoglobulin (IgA) and cytokine production29 could help to reduce susceptibility to infections.
To date, several studies have supported the relationship between probiotic use and decreased risk of mortality and NEC, which have been attributed to increased number of Lactobacillus and Bifidobacterium in the gut of preterm neonates.30 This has been supported by the results of recently conducted meta-analysis, which demonstrated a significant reduction in the incidence of NEC and death in infants given a Lactobacillus containing probiotic.31
Interestingly, a network meta-analysis assessing the best prevention strategy for necrotising enterocolitis in preterm infants concluded that a probiotic mixture and Bifidobacterium led to a greater reduction in incidence than Lactobacilli, Bacillus or Saccharomyces.32 This was explained by the ability of Bifidobacterium to create resistance to opportunistic pathogens and improvement of the mucosal and systemic immune system responses.33
Although the above studies did not find any adverse effects related to probiotic supplementation, it has been reported that probiotics may have the potential to cause probiotic-related sepsis. In order to minimise risks and enhance benefits, the use of non-viable microbial cells (intact or broken) or crude cell extracts, known as paraprobiotics, should be considered as a potential alternative. However, more clinical trials on this topic are necessary.34

References

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