MILESTONES

Microbiota succession in early life

Nature Reviews Microbiology

Search for this author in:

Credit: S. Bradbrook / Springer Nature Limited

Early life experiences have complex and long-lasting effects that can reach into adulthood — the same can be said of the acquisition and succession of our microbiota during the first years of life. The culmination of years of investigation from many laboratories has led to an in-depth characterization of postnatal microbial acquisition and maturation during the first years of life, and has led to the realisation that this represents a crucial window in our long-term development.

Early studies, dating as far back as 1900, described various aspects of bacterial succession in infants, but in 1981, three studies were reported that set out to quantitatively characterize early acquisition of gut commensals and to study how feeding shapes our initial microbiota. In one study, development of the bacterial community was investigated in infants in Sheffield, England, by culturing specimens taken from the meconium (a baby’s first faeces), faeces, mouth and umbilicus in the first six days of life. In another study, the faecal bacterial community was compared between infant cohorts in France that were either bottle-fed or breastfed; and in the third study, faecal bacterial communities from breastfed infants, weaned children and adults born in urban England and rural Nigeria, were compared. These studies provided quantitative measurements of specific bacterial taxa in early life, giving insight into the pioneer species that colonize the infant gut. This paved the way for future high-resolution studies of microbial succession in infants.

With the advent of ‘omics’ technologies in the following decades, our understanding of when the majority of our microbiota are acquired, and of what species are there, has heightened and the importance of host–microbiota–environment interactions during early life has become realised. The infant gut microbiota undergoes a period of massive change in the first years of life. The initial microbiota adapts over time and is shaped by the availability of different nutrients. As the infant consumes increasingly more complex dietary substrates, there are shifts in composition and an enrichment of bacterial functions related to carbohydrate metabolism and the biosynthesis of amino acids and vitamins. By 2–3 years of age, a stable microbiota develops that resembles that of the adults in the infant’s community (see Milestone 7).

When colonization first occurs is an open question; however, most scientists think that the foetus develops in a sterile environment and that we acquire the bulk of our initial microbiota during and immediately after birth. Recently, a few studies have found traces of bacterial DNA in the placenta, in the amniotic fluid that surrounds the foetus and in the meconium — suggesting prenatal colonization. However, many scientists think these findings could be the result of contamination and the debate is ongoing. Regardless of possible exposure to microorganisms in utero, the foetus is exposed to microbial molecules that cross the placenta from the mother.

The first major exposure to microorganisms happens during delivery, and is highly dependent on the mode of delivery. The microbiota of neonates that are born vaginally are enriched in bacteria that resemble the maternal vaginal microbiota (for example, Lactobacillus species), whereas neonates delivered by caesarean (C-) section lack these species and are instead enriched in skin commensals such as Staphylococcus, Streptococcus and Propionibacterium species. Over time, these differences gradually reduce between vaginally and C-section-born infants; however, in one study, bacteria associated with C-section remained associated with C-section-delivered infants up to two years of age, showing that birth mode could have long-term impacts on the microbiota.

Postnatal factors further configure the microbiota in early life. Breastmilk contains a complex community of bacteria that may help seed the infant gut microbiota, and in breastfed infants the gut microbiota is dominated by species that metabolise human milk oligosaccharides. Overall, diet has been found to be a major determinant of the infant gut microbiota. Studies of malnourished infants have shown that maturation of the gut microbiota does not occur in a similar manner to healthy infants, even after dietary intervention, and it has been proposed that an ‘undernourished’ microbiome in infancy can perpetuate growth impairments later in life.

The environment and people that surround an infant are also a source of microorganisms that can colonize various body sites. Genetically unrelated parents and even pets share a high proportion of their microbiota with infants. Genetics also has a role in determining our microbiota make-up, as evidenced by associations between the heritability of specific taxa and host genes.

The use of antimicrobials, which is essential for preserving life when infants acquire a serious bacterial infection, can impact the ecological succession of the infant microbiota. Antibiotics can impair the diversity and stability of the developing microbiota in infants, with abundances of specific taxa remaining reduced for years after treatment. The impact of antibiotics on the infant microbiota could have long-lasting health implications and their use in early life has been linked to an increased risk of several diseases, including asthma, inflammatory bowel disease and allergies (see Milestone 9). More research is required to uncover the underlying mechanisms; however, what is clear is that the microbiota has a vital role in immune, endocrine, metabolic and a variety of other developmental pathways in infants, and without it we would not be here today.

Further reading

Tamburini, S., Shen, N., Wu, H. C. & Clemente, J. C. The microbiome in early life: implications for health outcomes. Nat. Med. 22, 713–722 (2016).

Robertson, R. C., Manges, A. R., Finlay, B. B. & Prendergast, A. J. The Human microbiome and child growth: first 1,000 days and beyond. Trends Microbiol. 27, 131–147 (2019).

Cooperstock, M. S. & Zedd, A. J. in Human Intestinal Microflora in Health and Disease (ed. Hentges, D. J.) Ch. 4 (Elsevier, 1983).

Tissier, H. Recherches sur la flore intestinale des nourrissons (état normal et pathologique) (Carre, G. & C. Naud, C., Paris, 1900).

Long, S. S. & Swenson, R. M. Development of anaerobic faecal flora in healthy newborn infants. J. Pediatr. 91, 298–301 (1977).

Simhon, A., Douglas, J. R., Drasar, B.S. & Soothill, J. F. Effect of feeding on infants’ faecal flora. Arch. Dis. Child 57, 54–58 (1982).

Stark, P. L. & Lee, A. The microbial ecology of the large bowel of breast-fed and formula-fed infants during the first year of life. J. Med. Microbiol. 15, 189–203 (1982).

Satokari, R., Vaughan, E. E., Favier, C., Edwards, C. & de Vos, W. M. Diversity of Bifidobacteria and Lactobacillus spp. in breast-fed and formula fed infants as assessed by 16S rDNA sequence differences. Microb. Ecol. Health Dis. 14, 97–105 (2002).

Palmer, C., Bik, E. M., DiGiulio, D. B., Relman, D. A. & Brown, P. O. Development of the human infant intestinal microbiota. PLoS Biol. 5, e177 (2007).

Bennet, R. & Nord, C. E. Development of the fecal anaerobic microflora after cesarean section and treatment with antibiotics in newborn infants. Infection 15, 332–336 (1987).

Dominguez-Bello, M.G. et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc. Natl Acad. Sci. USA 107, 11971–11975 (2010).

Bäckhed, F. et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 17, 690–703 (2015).

Dominguez-Bello, M. G. et al. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat. Med. 22, 250–253 (2016).

Jakobsson, H.E. et al. Decreased gut microbiota diversity, delayed Bacteroidetes colonization and reduced TH1 responses in infants delivered by cesarean section. Gut 63, 559–566 (2014).

Koenig, J. E. et al. Succession of microbial consortia in the developing infant gut microbiome. Proc. Natl Acad. Sci. USA 108, 4578–4585 (2011).

Lim, E. S. et al. Early-life dynamics of the human gut virome and bacterial microbiome in infants. Nat. Med. 21, 1228–1234 (2015).

Yatsunenko, T. et al. Human gut microbiome viewed across age and geography. Nature 486, 222–227 (2012).

Bokulich, N. A. et al. Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci. Transl Med. 8, 343ra82 (2016).

Chu, D. M. et al. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nat. Med. 23, 314–326 (2017).

Wampach, L. et al. Colonization and succession within the human gut microbiome by archaea, bacteria and microeukaryotes during the first year of life. Front. Microbiol. 8, 738 (2017).

Stewart, C. J. et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature 562, 583–588 (2018).

Vatanen, T. et al. Genomic variation and strain-specific functional adaptation in the human gut microbiome during early life. Nat. Microbiol. 4, 470–479 (2018).

Yassour, M. et al. Strain-level analysis of mother-to-child bacterial transmission during the first few months of life. Cell Host Microbe 24, 146–154 (2018).

Ferretti, P. et al. Mother-to-infant microbial transmission from different body sites shapes the developing infant gut microbiome. Cell Host Microbe 24, 133–145 (2018).

Wampach, L. et al. Birth mode is associated with earliest strain-conferred gut microbiome functions and immunostimulatory potential. Nat. Commun. 9, 5091 (2018).

Aagaard, K. et al. The placenta harbors a unique microbiome. Sci. Transl. Med. 6, 237ra265 (2014).

Kliman, H.J. Comment on “The placenta harbors a unique microbiome”. Sci. Transl. Med. 6, 254le4 (2014).

Subramanian, S. Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature 510, 417–421 (2014).

Nature Briefing

An essential round-up of science news, opinion and analysis, delivered to your inbox every weekday.