How nutrition and the maternal microbiota shape the neonatal immune system

Key Points

  • The maternal microbiota itself affects the development of the fetus and the neonate.

  • Metabolic exposure of the fetus in utero depends on maternal nutrition and xenobiotic exposure, both of which are modulated by microbial metabolism.

  • Molecules that originate from the intestinal microorganisms of a mother reach her offspring via the placenta during fetal development, and through maternal milk during the postnatal period.

  • Maternal antibodies amplify microbial molecular transfer, both in utero and during lactation.

  • Signalling from maternal microbial molecules shapes the development and function of the immune system in early life.


The mucosal surfaces of mammals are densely colonized with microorganisms that are commonly referred to as the commensal microbiota. It is believed that the fetus in utero is sterile and that colonization with microorganisms starts only after birth. Nevertheless, the unborn fetus is exposed to a multitude of metabolites that originate from the commensal microbiota of the mother that reach systemic sites of the maternal body. The intestinal microbiota is strongly personalized and influenced by environmental factors, including nutrition. Members of the maternal microbiota can metabolize dietary components, pharmaceuticals and toxins, which can subsequently be passed to the developing fetus or the breast-feeding neonate. In this Review, we discuss the complex interplay between nutrition, the maternal microbiota and ingested chemicals, and summarize their effects on immunity in the offspring.

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Figure 1: Maternal stress weakens maternal and offspring immunity.
Figure 2: Placental development and fetal haematopoiesis.
Figure 3: A schematic of the effects of the maternal microbiota and maternal nutrition on immune development in the offspring.
Figure 4: Epigenetic reprogramming during mammalian development.


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The authors thank colleagues in their laboratory and U. Sauer, W. Hardt and C. Mueller for helpful discussions on the topic. The work of A.J.M. is funded by grants from the Swiss National Science Foundation (SNSF 310030B_160262 and SNSF Sinergia CRSII3_154414) and the Swiss SystemsX programme (GutX)); M.G.A. holds an Ambizione Grant of the Swiss National Science Foundation (PZ00P3_168012); and S.C.G.-V. is supported by a European Molecular Biology Organization Long-Term Fellowship (ALTF 841–2013).

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Correspondence to Andrew J. Macpherson or Stephanie C. Ganal-Vonarburg.

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A drug that was prescribed primarily as a sedative or hypnotic. It was used to treat nausea and to cure morning sickness in pregnant women until it was discovered that it caused an absence of limbs in the offspring at birth.

Hypothalamic–pituitary–adrenal axis

(HPA axis). One of the major neuroendocrine systems that controls, among other things, reactions to stress, the immune system, digestion and emotions. It consists of a complex set of feedforward and feedback mechanisms between the hypothalamus, the pituitary gland and the adrenal cortex. Neuroendocrine neurons in the hypothalamus produce corticotropin-releasing factor, which acts on the anterior pituitary gland to induce the production of adrenocorticotropic hormone (ACTH). ACTH induces the adrenal gland to release glucocorticoids, such as cortisol.


The eating of faeces, which is a normal behaviour in many animals.

Haemochorial placenta

A type of placenta present in humans and some rodents, in which maternal blood is in direct contact with the chorion.


A bag-like structure that forms part of the developing conceptus and that has a role in nutrition and excretion.

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Macpherson, A., de Agüero, M. & Ganal-Vonarburg, S. How nutrition and the maternal microbiota shape the neonatal immune system. Nat Rev Immunol 17, 508–517 (2017).

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