Abstract
Prenatal and early postnatal life represent key periods of immune system development. In addition to genetics and host biology, environment has a large and irreversible role in the immune maturation and health of an infant. One key player in this process is the gut microbiota, a diverse community of microorganisms that colonizes the human intestine. The diet, environment and medical interventions experienced by an infant determine the establishment and progression of the intestinal microbiota, which interacts with and trains the developing immune system. Several chronic immune-mediated diseases have been linked to an altered gut microbiota during early infancy. The recent rise in allergic disease incidence has been explained by the ‘hygiene hypothesis’, which states that societal changes in developed countries have led to reduced early-life microbial exposures, negatively impacting immunity. Although human cohort studies across the globe have established a correlation between early-life microbiota composition and atopy, mechanistic links and specific host–microorganism interactions are still being uncovered. Here, we detail the progression of immune system and microbiota maturation in early life, highlight the mechanistic links between microbes and the immune system, and summarize the role of early-life host–microorganism interactions in allergic disease development.
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Acknowledgements
B.B.F’s lab is supported by a Canadian Institutes for Health Research (CIHR) Foundation Grant. B.B.F. is also a Canadian Institute for Advanced Research (CIFAR) Senior Fellow. K.D. is supported by the Four Year Fellowship Tuition Award, President’s Academic Excellence Initiative PhD Award and International Tuition Award at the University of British Columbia.
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Glossary
- Germ-free mice
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(GF mice). Mice that are kept in sterile conditions and are devoid of microbes, often used to study what happens in the absence of a microbiota.
- Hygiene hypothesis
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Hypothesis stating that reduced contact with environmental microbes has contributed to the recent rise in immune-mediated diseases.
- Isolated lymphoid follicles
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Organized centres of lymphoid tissue lining the intestine.
- Paneth cells
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Cells that line the intestine and modulate the gut microbiota; important producers of antimicrobial peptides.
- Polymeric Ig receptor
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(PIgR). Receptor responsible for carrying antibodies including IgA across mucosal surfaces for secretion into the lumen; donates a peptide to secreted antibodies and contributes to antibody stability.
- Window of opportunity
-
Period of early life when the immune system is still developing and is susceptible to the influence of microbes and environmental factors, affecting lifelong immunity; often thought to be represented by the first 3 months after birth.
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Donald, K., Finlay, B.B. Early-life interactions between the microbiota and immune system: impact on immune system development and atopic disease. Nat Rev Immunol 23, 735–748 (2023). https://doi.org/10.1038/s41577-023-00874-w
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DOI: https://doi.org/10.1038/s41577-023-00874-w