Page 76 - Read Online

Page 2 of 19 van Beek et al. Microbiome Res Rep 2025;4:13 https://dx.doi.org/10.20517/mrr.2024.45

Conclusion: There is an age-associated development in the correlation pattern between bacterial population
growth and the biomarker concentrations, suggesting that host-microbe interactions change during early
development. Albumin appeared as a potential marker of gut permeability, while LCN2 seemed to correlate with
gut transit time. Mucin degradation appeared to decrease with age. Mucin2 and IAP emerged as potentially
important regulators of the bacterial populations in the infant gut. The study demonstrates the utility of biomarker
and bacteria profiling from daily stool samples for analysing in vivo associations between the immune system and
the gut microbiota and provides evidence of host regulation of the microbiota in infants.

Keywords: Infant gut microbiome, immune biomarkers, IAP, mucin, lipocalin 2, albumin

INTRODUCTION
The human body is a bustling metropolis of microorganisms collectively known as the microbiota. The
To regulate the infant microbiome for health purposes, understanding the determinants of microbiota
microbiota includes fungi, bacteria, archaea, and bacteriophages, with bacteria forming the most abundant
taxonomic group. In the human gut, the main bacterial species are members of the phyla Firmicutes,
[1]
Bacteroidetes, Proteobacteria, Actinobacteria, and Verrucomicrobia .

The microbiota of an individual begins to form at birth, with significant colonisation happening at the
moment of birth. During vaginal birth, the infant receives microbes from the mother, which lays the
groundwork for microbiota development . After the initial seeding, the composition of the gut microbiome
[2]
is influenced by everything the infant is exposed to, mainly what they consume, including solid foods .
[3,4]
The gut microbiome is involved in many vital facets of life, such as digestion and regulation of metabolism
and the immune system . Dysregulation of the microbiota is associated with a wide range of diseases, both
[5]
during infancy and later in life, including metabolic diseases, allergic and chronic inflammatory diseases .
[5,6]
Infants are born with an immature immune system , making them vulnerable to infectious diseases within
[7]
the first months of life. The infant gut microbiota can prevent pathogen colonisation and help train the
immune system. Importantly, the infant gut microbiota impacts the later health of the host by affecting the
development of the host’s physiology. Aberrations in the infant gut microbiota development are linked to
the later onset of immune disorders such as atopic dermatitis (eczema), inflammatory bowel disease (IBD),
[5,8]
and asthma, as well as obesity . Because factors influencing the infant’s gut microbiome also impact the
infant’s future health, ensuring a healthy infant microbiome, regardless of external factors such as birth
method and feeding style, can be a cost-effective and promising approach to preventing later health issues.

composition is essential. Most of the interindividual variation in gut microbiota composition in infants is
still unexplained - studies have shown that approximately 20%-30% of the variation can be explained by
external factors, such as birth mode, diet, and antibiotic exposure [9,10] . It is assumed that host-specific factors
are important in regulating the gut microbiota, but these are poorly understood. The host influences the
microbiome through dietary exposures and genetic factors. Quantitative trait loci (QTLs) that affect the
microbiome are immune- or metabolism-related. Notably, the ABO (A, B antigens) and LCT locus (lactase)
explain a small percentage of microbiota variance consistently across multiple GWAS . How the gut
[11]
microbiota interacts with the infant’s immature immune system and how the immune system, in turn,
affects the abundance and composition of the microbiota have not been extensively studied.