Childhood Development and the Microbiome-The Intestinal Microbiota in Maintenance of Health and Development of Disease During Childhood Development

Abstract

The composition of the intestinal microbiome affects health from the prenatal period throughout childhood, and many diseases have been associated with dysbiosis. The gut microbiome is constantly changing, from birth throughout adulthood, and several variables affect its development and content. Features of the intestinal microbiota can affect development of the brain, immune system, and lungs, as well as body growth. We review the development of the gut microbiome, proponents of dysbiosis, and interactions of the microbiota with other organs. The gut microbiome should be thought of as an organ system that has important effects on childhood development. Dysbiosis has been associated with diseases in children and adults, including autism, attention deficit hyperactivity disorder, asthma, and allergies.

Keywords: Childhood Development; Childhood Diseases; Gut Microbiome; Infancy; Microbiota.

Figure 1.. Factors influencing Microbiome development throughout childhood

For simplicity, this figure represents the most commonly proposed dominant taxa of a healthy full-term breast fed infant along with the events of childhood or exposures which likely contribute to alterations in taxa predominance (112, 113). A comparison of Adult gut microbiome and that of the developing microbiome throughout childhood shows there is a temporal progression. The microbiome in infancy is less diverse and less stable than that of an adult. The microbiome of an infant is dependent on many factors- mode of delivery, milk consumption, medication exposure, environment. Weaning signals a significant change in diet, after which Proteobacteria become far less abundant. During childhood years the diversity increases as does the stability. By adolescence the gut microbiome does not yet resemble that of an adult but does show a shift toward an overall decrease in numbers of aerobes and facultative anaerobes, as well as concurrent increases in anaerobic species (113, 114). While the exact population and shifts may not yet be known, it is clear that environmental and physiologic triggers induce changes.

Figure 2. Parallel neurodevelopment and microbiome development during childhood

Astrogliogenesis begins in utero and continues until approximately 2 years. Astrocytes function to shape neural circuits in the developing brain by coordinating synapse formation and function, neuronal survival, and axon guidance. Oligodendrogenesis continues from the prenatal period through 4 years and is responsible for myelin sheath production. Myelination occurs from birth through 8 years, with 80% of adult myelination being achieved between ages 2–3 years. Synaptogenesis begins prenatally and continues through 4 years, with synaptic pruning occurring from 3 years through 10 years. Here we can see the microbiotal changes that are occurring concurrently with neurodevelopment. The periods of highest growth and plasticity represent crucial windows in which the gut-brain axis can be impacted (115, 116, 117, 118).

Figure 3. Proposed mechanisms of bi- and uni-directional communication from gut microbiome to various organ systems impacting child health and disease

While the exact mechanisms of communication are yet to be understood, these are the most commonly hypothesized pathways. Communication can occur along nerve fibers, hormonal axes and via mediation of many different cytokines, bioactive amines, microbe-associated molecular patterns (MAMP) and short chain fatty acids.