Early Life Microbiome trajectory and its influencers

Author(s):
Shaillay Kumar Dogra

Key messages:

• The gut microbiome in infants evolves progressively towards an adult-like microbiome.
• Early Life Microbiome (ELM) maturation can be described by different methods that simplify the description of the entire microbiome; here, we focus on the trajectory approach.
• The ELM trajectory is influenced by many factors. Nutrition is a critical modulator of the microbiome.

Early life microbiome development

The infant gut microbiome is a dynamic ecosystem that undergoes changes from birth until two to three years of age, followed by a gradual evolution towards an adult microbiome in later childhood.1

As per increasing scientific evidence, it is believed that the early life microbiome (ELM) establishment has lasting consequences on lifelong health.2 To simplify the depiction and interpretation of the rapidly evolving infant gut microbiome, one approach links the development of the early life microbiome with infant age, and follows a similar statistical framework as the WHO growth curves to inform individual infant microbiome development as compared to the reference trajectory.3

First, a set of infants is chosen as “reference” based on certain criteria such as delivery mode, at term birth, exclusive breastfeeding duration, infant growth characteristics, and health/ disease status. Then, a machine learning model is applied to predict age
using the microbiome data. The microbiome-based predicted age from an infant’s fecal sample is compared to the reference for the same age allowing for natural variation. Microbiome development of this infant is considered normal if it falls within the reference trajectory.

Factors that influence the early life microbiome

Factors such as mode of birth, antibiotic usage and type of feeding impact the ELM profile compared to the reference.4, 5 Other factors such as geography, rural or urban living, number of siblings and weaning diet may also influence infant microbiome development4, 6 (Figure 1b).

Some of these factors such as mode of birth or antibiotic usage have been directly associated with later health outcomes7, 8 and it is possible that some mechanisms are mediated through alterations in the microbiome.9

Importantly, it is possible to nutritionally intervene in order to modulate the
microbiome closer to the reference trajectory.3, 10 For example, certain species of Bifidobacterium, which are important components of the infant gut microbiome in the first few months of life, benefit from Human Milk Oligosaccharides (HMOs).11

Faecalibacterium prausnitzii, a bacterium that establishes in the infant gut from about nine months onwards to become a predominant member of the gut microbiome, utilizes fibers to generate butyrate that is an important health associated metabolite.12

In summary, the infant gut microbiome evolves rapidly and is influenced by various factors, some of which are linked to allergy development or poor metabolic health outcomes later in life. The microbiome trajectory description can differentiate several factors influencing the ELM such as mode of birth, breastfeeding practice and nutrition. Importantly, nutritional interventions can modulate the microbiome maturation towards the reference trajectory.3, 10

Acknowledgements:
Sincere thanks are due to Dr. Norbert Sprenger and Dr. Olga Sakwinska for providing valuable suggestions and critical remarks that much enhanced this article.


 
References
1. Cher A, Yassour M. Chapter 8 - The compositional development of the microbiome in early life. The Human Microbiome in Early Life: Implications to Health and Disease, 2020 (ISBN 978-0-12-818097-6).
2. Dogra S, et al. Rate of establishing the gut microbiota in infancy has consequences for future health. Gut Microbes. 2015;6(5):321-5.
3. Subramanian S, et al. Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature. 2014 Jun 19;510(7505):417-21.
4. Stewart CJ, et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature. 2018 Oct;562(7728):583-588.
5. Ho NT, et al. Meta-analysis of effects of exclusive breastfeeding on infant gut
microbiota across populations. Nat Commun. 2018 Oct 9;9(1):4169.
6. Kemppainen KM, et al. TEDDY Study Group. Early childhood gut microbiomes show strong geographic differences among subjects at high risk for type 1 diabetes. Diabetes Care. 2015 Feb;38(2):329-32.
7. Sandall J, et al. Short-term and long-term effects of caesarean section on the health of women and children. Lancet. 2018 Oct 13;392(10155):1349-1357.
8. Aversa Z, et al. Association of Infant Antibiotic Exposure With Childhood Health Outcomes. Mayo Clin Proc. 2021 Jan;96(1):66-77.
9. Stiemsma LT, Michels KB. The Role of the Microbiome in the Developmental Origins of Health and Disease. Pediatrics. 2018 Apr;141(4):e20172437.
10. Gehrig JL, et al. Effects of microbiota-directed foods in gnotobiotic animals and
undernourished children. Science. 2019 Jul 12;365(6449):eaau4732.
11. Berger B, et al. Linking Human Milk Oligosaccharides, Infant Fecal Community Types, and Later Risk To Require Antibiotics. mBio. 2020 Mar 17;11(2):e03196-19.
12. Louis P, Flint HJ. Formation of propionate and butyrate by the human colonic microbiota. Environ Microbiol. 2017 Jan;19(1):29-41.