Vast numbers of bacteria, viruses, and fungi (collectively known as the microbiome) live in and on the human body and play an important role in maintaining our health and wellbeing1,2,3,4,5,6. Microbes outnumber our human cells and therefore the genes that are transmitted from parents to infants are predominantly microbial. It has been estimated that only 1 percent of genetic transfer is human5, with the genes of microbes – the ‘second human genome’6 – making up the rest. Thus, rather than being a single stand-alone species, humans are more properly understood to be superorganisms made up of thousands of biologically diverse species4. The microbiome contributes significantly to individual differences between us: while humans are relatively homogeneous in their genetic makeup, we vary greatly in the composition of microbiomes, with only a third of the microbiome’s constituent genes found in a majority of healthy individuals7,8. 

The diverse ecology of microbes that make up the microbiome has coevolved with our species over millennia1,9.  These microbes provide us with essential services in exchange for being housed and fed. In particular, it is the bacteria in our gut that play a critical role in our physical and even our mental health2,1,5. The beneficial functions they perform include helping digest food components that our guts cannot process (including essential elements in breastmilk), regulating our bodies’ metabolisms, producing hormones, detoxifying dangerous chemicals we ingest with our food, training and regulating the immune system, and preventing the invasion and growth of dangerous pathogens5.

By virtue of its ability to confer an extensive set of protective and functional benefits to its human host, the gut microbiome can be considered a microbial or metabolic ‘organ’, and maintaining the proper health and functionality of this ‘organ’ is of significant importance10. In short, it is the microbiome that helps keep us healthy2. The brain, the gut, and the microbiome are in constant close communication, and function as parts of a single integrated system – the brain-gut-microbiome axis5. The first 1000 days are particularly crucial in shaping the architecture of this axis: both the brain and the microbiome are still developing, and changes during this period tend to persist for life. The consequences may not emerge until later in life, when the diversity and resilience of the gut microbiome decreases, making us vulnerable to degenerative diseases such as Alzheimer’s or Parkinson’s disease5. 

Any change in the abundance, or composition or diversity of these micro-organisms can have significant health consequences. For instance, it may lead to failures to regulate and restore appropriate immune and inflammatory responses1,10,11, which can contribute to chronic inflammatory conditions such as inflammatory bowel disease and asthma, and may even play a role in the development of conditions such as autism spectrum disorder, psychiatric disorders such as depression, and neurodegenerative conditions such as Parkinson’s disease12,1,10,5,13,14. Since the traffic on the brain-gut-microbiome axis is two-way, our mental states can shape the composition of our gut bacteria. For instance, one study found that the infants of mothers who experience cumulative stress during pregnancy show marked disturbances in the composition of their gut bacteria, and subsequently have more health problems, such as infant gastrointestinal symptoms and allergic reactions15. 

Disturbances of the composition of the microbiome – known as dysbiosis – can take several forms: a loss of beneficial microbes, an expansion of harmful microbes, or a loss of overall microbial diversity16,9,17. Logan16 suggests that the conditions promoting dysbiosis are unequally distributed across society, with those living in socioeconomically deprived conditions where grey space (as opposed to green space) is the dominant environmental feature being more likely to be experiencing dysbiosis.

The two sources of microbial exposure that are important for human health and development – environmental and human microbiota – have both become less diverse as a result of modern lifestyle changes. In addition, environmental changes such as urbanisation, higher exposure to chemicals and less exposure to green spaces, have reduced our exposure to a diverse range of plant, animal and microbial life. This has been linked with a range of mismatch diseases, including allergies, and Type 1 diabetes1 and asthma18,19. Our developmental health is also at risk because parts of our ancestral microbiome are disappearing20. This is due to a range or factors, including overuse of antibiotics (in treating humans and in promoting the growth of the animals we eat)21,22, overuse of caesarean section births when not strictly necessary, the widespread use of sanitisers and antiseptics, and the shift to a Westernized high-fat high-carbohydrate high-fructose diet23,10,24. As Mayer5 notes, it is easier to reduce gut microbial diversity in adults than it is to increase it above the level established in the first 1000 days. 

Although the womb was thought to provide a sterile environment for the foetus, we now know that some bacteria are able to cross the placenta25, although we know very little about the nature and impact of microbes that do so. What we do know is that, from birth onwards, infants are rapidly colonised by a remarkably wide diversity of bacteria. In the case of the colonisation of the gut, the composition of gut microbiota in infants is markedly different from those in adults, but becomes progressively more adult-like as the infant acquires more microbes from the people around them, and reaches an adult-like form by the age of three26. Thus, the transition from no microbiota to an adult-like microbiome is all accomplished during the first 1000 days or so of life2,9. 

Just as the human epigenome is developmentally programmed by the early environment, so too is the human microbiome9. In the postnatal period, microbial colonisation is influenced by factors such as gestational age, antibiotic exposure, delivery mode (caesarean section delays and laters the establishment of the gut microbiome), breastfeeding, formula milks, timing and types of solid foods, and genetic factors9,25. The importance of acquiring a full complement of microbiota in the early years is captured in the self-completion hypothesis – which maintains that the single, most pivotal sign in distinguishing a life course of health versus that filled with disease is a successful and timely ‘seeding’ with an optimal complement of microbiota27,28,4. There appears to be a narrow developmental window for effective seeding surrounding birth, and the completion of the full microbiome over the next two and a half to three years shapes their gut microbiome for a lifetime5,29. The immune dysregulation created by missing gut microbes during key periods of immune maturation can remain into adulthood27 and act as a biomarker of specific health risks27. 

The microbiome evidence is another form of mismatch. The developing immune system appears to be particularly susceptible to modern environmental change, with the most common and earliest developing non-communicable diseases being immune-related conditions such as allergies30 and obesity31.