Prebiotics & Probiotics and the Gut Microbiota

Prebiotics are defined as selectively fermented compounds that result in positive changes in the composition and/or activity of the gut microbiota, and by doing so, provide health benefits(1). Prebiotics are essentially indigestible oligosaccharides that escape digestion in the small intestine, and selectively feed the indigenous microbiota (probiotics) in the large intestine(2).

Probiotics are defined as living microorganisms that, when administered in adequate amounts, provide some health benefit to the person receiving them(1). Essentially, they are living, beneficial and healthy bacteria that help to create a healthy gut bacteria profile.

Humans have a remarkably large microbial ecosystem, comprising bacteria, viruses and fungi(3), which is influenced by environmental factors, including the use of antibiotics and food intake(3, 4). A healthy gut microbiota is characterised by a diverse mix of gut bacteria and a suitable balance between ‘beneficial’ and ‘harmful’ gut microbes.

Clinical researchers are starting to appreciate the many roles these organisms play in human health and development, at least partly driven by recent molecular technologies that enable rapid identification and enumeration of colonic bacteria(2). There is widespread agreement that a healthy gut microbiota, which is seeded during the first 1000 days of life, has important health implications across the lifespan, with beneficial nutrition, immunological and developmental effects reported.

Gut Microbiota in Adults

The human intestinal microbiota is dynamic and changes throughout life. In healthy adults, most of the intestinal bacteria reside in the large bowel microbiota, where the population is diverse (with hundreds of bacterial species) and numerous, with the number of bacterial cells exceeding those of the host(3, 5).

The adult microbiota is predominately composed of obligate anaerobes (i.e. they do not survive in the presence of oxygen)(6). It engages in complex functions and produces various biologically important by-products or compounds, including short chain fatty acids like butyrate (mediator of colonic health) and enzymes important in the metabolism of several vitamins(4, 7, 8). In adults, the dominant bacteria phyla are Bacteroidetes and Firmicutes(9).

What about during pregnancy and in babies?

Pregnancy: It is widely reported that an infant’s gut is sterile (i.e. germ free) when he or she is born, at which time an infant is exposed to their mother’s microbiota during birth(10). However, evidence suggests a prenatal effect on an infant’s microbial composition(5, 10)   and that the maternal microbiota is emerging as potential risk or protective factor for allergic disease in the offspring.

During pregnancy, there are noticeable changes in the microbiota at different body sites, changes which shape the development of the microbiota and immune system in the offspring(5). Changes in the gut microbiota composition are characterised by an increased abundance in members of the Actinobacteria and Proteobacteria phyla, as well as a reduction in individual richness.

The vaginal microbiota also undergoes substantial change during pregnancy, with a reduction in the overall diversity and richness, together with the relative dominance of the Lactobacillus species taking root(11, 12). These bacteria are facultative anaerobes, known generally as lactic acid bacteria. Some lactobacillus species have bactericidal activities against other species, which ensures their dominance and which may help protect against infection during pregnancy(5, 13).

The Early Life Coalition highlights that dietary Prebiotics and Probiotics are key dietary nutrients during pregnancy, because of their influence on maternal gut microbiota.

Infancy: The most important factors that shape an infant’s gut microbiota include the mode of delivery and the method of feeding (i.e. breastfeeding compared with formula feeding and then solid foods), with gestational age also playing a role(3, 19).

The newborn intestine at birth is an aerobic environment, where only facultative anaerobes such as members of the Enterobacteriaceae family can grow(14). In a matter of days, the intestinal lumen turns anaerobic, which allows for strict anaerobes like Bifidobacterium to flourish (Figure 1)(14). The infant gut becomes progressively more dominated by Bifidobacterium and Lactobacillus bacteria (i.e.  lactic acid producing bacteria) during the early months of life (Figure 1)(3, 14-16). While there are differences between formula and breast fed infants in these early months, the transition to solid food plays a significant role in shaping the gut bacteria composition in all infants and around this time, the infant’s gut microbiota becomes seeded with species prevalent in adults.

intestinal microbial colonisation

Figure 1: The intestinal microbiota of the newborn is initially colonised by Enterobacteria. Within days and during during the first month, Bacteroidaceae and Lactobacilleace (Bifidobacteria and Lactobacillus species) colonise and dominate, with expansion of Lachnospiracea, Clostridiaceae and Ruminococcaceae at around 6 months, as solid food is introduced. Members of the Ruminococcaceae family continue to proliferate in the following months. By 2-3 years of age, the microbiota composition consists mainly of Bacteroidaceae, Lachnospiraceae and Ruminococcaceae, which then remains stable into adulthood. Image adapted from reference(14).

In Caesarian Section born infants, the gut microbiota shows resemblance to the maternal skin and oral microbiota(17, 18). Infants born by Caesarian Section also exhibit delayed colonisation of bacteria from the Bacteroidetes phylum. However, these differences in species diversity almost disappear by 12 months of age(5, 17), around which time there is a shift towards adult-like gut bacteria profiles to include members of the Bacteroidetes and Firmicutes phyla(3, 19).

While the temporal shifts of these developments varies between babies, with differences observed both within and between breastfed and formula fed babies(3, 15), the differences exist within these broad common patterns observed in infants as a whole(3).

Prebiotics & Probiotics

Prebiotics: Human breast milk contains many complex prebiotics, called human milk oligosaccharides (HMO), which make up around one third of the composition of breast milk(20). These HMOs have been shown to have important health effects on the developing baby, including benefits to the infant’s immune system and gut bacteria(20). The Bifidobacterium and Lactobacillus bacteria that dominate the infant’s gut microbiota during the first year, grow robustly on human milk oligosaccharides(20). Prebiotics also help maintain softer stools, helping to keep babies regular(21). This may be because galactooligosaccharides increase levels of the beneficial bifidobacterium(22).

Research on the composition of human breast milk oligosaccharides and their relevance to the infant gut microbiota highlight the value of prebiotic oligosaccharides during early life nutrition(21).

Probiotics: Like breast milk and prebiotics, breast milk also contains its own probiotics(23). Lactating mothers pass these probiotics onto their feeding infants.

In babies, supplementation with the probiotic called Bifidobacterium lactis Bb12 has been shown to significantly reduce the number of episodes of gastrointestinal infections relative to not having the probiotics(24). 

However, according to two recent large randomised controlled trials, Lactobacillus rhamnosus probiotics given to children with acute gastroenteritis do not hasten recovery .

References

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  2. Rastall RA. Bacteria in the gut: friends and foes and how to alter the balance. Journal Nutrition. 2004;134(8 Suppl):2022S-6S. Access link.
  3. Palmer C, Bik EM, DiGiulio DB, et al. Development of the human infant intestinal microbiota. PLoS Biology. 2007;5(7):e177. Access link.
  4. Gorbach SL. Microbiology of the Gastrointestinal Tract. In: Baron S, Editors. Medical Microbiology. Galveston (TX), 1996. Access link.
  5. Nuriel-Ohayon M, Neuman H, Koren O. Microbial Changes during Pregnancy, Birth, and Infancy. Frontiers in Microbiology. 2016;7:1031. Access link.
  6. Maier E, Anderson RC, Roy NC. Understanding how commensal obligate anaerobic bacteria regulate immune functions in the large intestine. Nutrients. 2014;7(1):45-73. Access link.
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  8. Topping D, Conlon MA. Feeding a hungry microbiome: large bowel fermentation and human health. Med J Aust. 2014;201(8):438. Access link.
  9. Rajilic-Stojanovic M, Heilig HG, Molenaar D, et al. 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. Environmental Microbiology. 2009;11(7):1736-51. Access link.
  10. Willyard C. Could baby’s first bacteria take root before birth? Nature. 2018;553(7688):264-6. Access link.
  11. Aagaard K, Riehle K, Ma J, et al. A metagenomic approach to characterization of the vaginal microbiome signature in pregnancy. PloS one. 2012;7(6):e36466. Access link.
  12. Favier CF, de Vos WM, Akkermans AD. Development of bacterial and bifidobacterial communities in feces of newborn babies. Anaerobe. 2003;9(5):219-29. Access Link.
  13. Spurbeck RR, Arvidson CG. Lactobacillus jensenii surface-associated proteins inhibit Neisseria gonorrhoeae adherence to epithelial cells. Infection and Immunity. 2010;78(7):3103-11. Access Link.
  14. Arrieta MC, Stiemsma LT, Amenyogbe N, et al. The intestinal microbiome in early life: health and disease. Frontiers in Immunology. 2014;5:427. Access Link.
  15. Obermajer T, Grabnar I, Benedik E, et al. Microbes in Infant Gut Development: Placing Abundance Within Environmental, Clinical and Growth Parameters. Scientific Reports. 2017;7(1):11230. Access Link.
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  18. MacIntyre DA, Chandiramani M, Lee YS, et al. The vaginal microbiome during pregnancy and the postpartum period in a European population. Scientific Reports. 2015;5:8988. Access Link.
  19. Stark PL, Lee A. The microbial ecology of the large bowel of breast-fed and formula-fed infants during the first year of life. J Medical Microbiology. 1982;15(2):189-203. Access Link.
  20. LoCascio RG, Desai P, Sela DA, et al. Broad conservation of milk utilization genes in Bifidobacterium longum subsp. infantis as revealed by comparative genomic hybridization. Applied & Environmental Microbiology. 2010;76(22):7373-81. Access Link.
  21. Skorka A, Piescik-Lech M, Kolodziej M, Szajewska H. Infant formulae supplemented with prebiotics: Are they better than unsupplemented formulae? An updated systematic review. The British J Nutrition. 2018;119(7):810-25. Access Link.
  22. Davis LM, Martinez I, Walter J, et al. Barcoded pyrosequencing reveals that consumption of galactooligosaccharides results in a highly specific bifidogenic response in humans. PloS one. 2011;6(9):e25200. Access Link.
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