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Page 2 of 20 Horwell et al. Microbiome Res Rep 2025;4:1 https://dx.doi.org/10.20517/mrr.2024.32

INTRODUCTION
The term “microbiome” was first coined by Professor John Whipps in 1988 to describe the microorganisms
[1]
living in soil . Colloquially, as well as in the scientific and medical lexicon, the term has
anthropomorphically shifted, with the assumption of reference being to the human microbial ecosystem
rather than the rhizosphere. The human microbiome is defined as the totality of microbial species found
living in and on a human - that is, all the species of bacteria, archaea, fungi, algae, small protists,
[2,3]
bacteriophages, and viruses, as well as extracellular DNA . It also encompasses their “theatre of activity” -
the secondary metabolites produced by these communities [e.g., toxins, lipopeptides, polysaccharides,
signalling molecules, and other (in)organic matter] that often have important metabolic and
immunogenic effects. The human microbiome is diverse, with populations differing greatly depending on
anatomical location. As an example, the species found in the alar crease are significantly different from
those in the inguinal crease, despite both being on the skin surface .
[4]
[13]
The human-microbiome symbiosis should be viewed as one of co-evolution, with the microbiome aiding in
the metabolism of food into short-chain fatty acids (SCFAs) (e.g., fermentation of the otherwise poorly
digested plant polysaccharides and unhydrolyzed starches), the production of vitamins (e.g., thiamine,
folate, riboflavin, pantothenic acid, biotin and vitamin K), and the control and competitive exclusion of
pathogenic bacteria . In response, the host provides a stable and rich environment with sophisticated
[5]
[6]
immunological mechanisms to sense and control specific species . Archaeological evidence from coprolites,
dental plaque and tissue stored in permafrost have provided insight into how our microbiome has shifted
away from that of the great apes to one of lower alpha diversity, with particularly decreased
Methanobrevibacter and Fibrobacter, and significantly more Bacteroides species . The recent (in
[7]
evolutionary timescales) agricultural revolution, adoption of using heat to cook food, and Westernised diet
(one of high meat and ultra-processed food consumption) have induced a rapid change in the makeup of
our microbiome, which appears to have introduced mal-adaptions that are involved in diseases of
[8,9]
modernity .
The contemporary literature reports some ~3.8 × 10 bacteria dwelling in the 70 kg “reference” male;
13
however, it is the colon that is the true microbial powerhouse, making up 92% of the total microbiome ,
[10]
and unless otherwise stated, hereon microbiome will be in reference to the human colonic microbiome. To
regulate this, the gastrointestinal tract (GIT) maintains a fine balance of immune regulation and,
accordingly, is the largest immune organ in the body . This complex system involves the sensing of
[11]
symbiotic species without stimulating the immune system, while detecting and mounting immune
[12]
responses to specific pathogens . If the interplay between this masterly inactivity and overactive defence
mechanisms goes astray, there are numerous negative health-related consequences, ranging from
inflammatory bowel disease (IBD), diabetes, cancer, obesity, cardiovascular disease, hypertension,
depression, and anxiety (to name but a few) . The “priming”, or education, of what the GIT immune
system should consider a pathogen is, therefore, vital for future health . The evidence suggests that this
[12]
process is largely determined during the first five years of life; thus, it is of the utmost importance to fully
understand and characterise the colonisation of a healthy microbiome during infancy.

Accordingly, this paper will review the latest literature on colonisation dynamics during the early years of
life and what variables are at play. Specifically, we will seek out the mechanistic evidence for how bacterial
species are transferred from one environment to the colonic microbiome of an individual, and discuss how
this can be potentially utilised for public health. We will discuss any gaps and limitations of the scientific