MIRACLE - Microbiota and children laboratory

The microbiota is a rich and diverse community of microorganisms that live on and in humans. The use of next generation sequencing technology, in particular shotgun sequencing, has expanded our understanding of the complexity of the human microbiota as it enables not only the identification of bacterial species, but also of antibiotic resistance genes, archaea, eukaryotes (fungi, helminths, and protozoans) and viruses. Growing evidence shows that the composition of the microbiota is associated with the development of many immune- and non-immune-mediated diseases, including allergic diseases, eczema, asthma, chronic inflammatory bowel disease, obesity and diabetes mellitus.

Growing evidence shows that the composition of the intestinal microbiota in infants plays an important role in the development and regulation of the immune system, especially in the early-life ‘critical window’ during which the microbiota and the immune response develop concurrently. The development of intestinal microbiota is easily disrupted by external factors and perturbation during this vulnerable period may have a large influence on immune development.

• Antibiotic use and the composition of the intestinal microbiota

  A number of factors influence the development of the infant intestinal microbiota, including gestational age, delivery mode, feeding, and maternal and infant antibiotic exposure. While the effect of delivery mode and feeding methods on the establishment of microbial communities has been well studied, much less is known about the effects of intrapartum and early-life antibiotic exposure on the establishment of microbial communities in the intestinal microbiota. Antibiotics are among to the most commonly used drugs, especially in infants and children. Even before birth, more than 40% of infants are already exposed to antibiotics. Additionally, it is estimated that more than two-thirds of children receive antibiotics before reaching the age of two years. The magnitude of the effect of intrapartum and early-life antibiotics on the intestinal microbiota, and whether effects are only short-term or persist long-term remain uncertain.

  In a prospective study, the ABERRANT study, we are investigating the effect of (i) intrapartum antibiotics on the composition of the infant intestinal microbiota and (ii) antibiotic exposure in the first two years of life on the composition of the intestinal microbiota.

  

• The breast milk microbiota

  Breastfeeding has been shown to be beneficial in preventing many communicable and non-communicable diseases. Despite intensive research into the positive health effects of breastfeeding, the underlying mechanisms are still not understood. A large part of the beneficial effects of breast milk is likely mediated through the microbiota and its associated immunomodulatory, anti-inflammatory and antimicrobial components. The breast milk microbiota also plays a large part in shaping the infant’s intestinal microbiota.

  In the ABERRANT study, we are investigating the effect of different factors (e.g. delivery mode, or intrapartum antibiotics) on the composition of the breast milk microbiota. Furthermore, we will also determine the association between the maternal intestinal microbiota, the breast milk microbiota, the infant oral and intestinal microbiota.

  We study the polarization of macrophage induced by a therapeutic cardiac bandage and its effect on cardiac repair and regeneration.

  

  Breast milk microbiota: A review of the factors that influence composition.
  Zimmermann P, Curtis N.
  Journal of Infection. 2020

• The prevalence of immune-mediated diseases and their link to the intestinal microbiota

  Over the last few decades, there has been a dramatic rise in the prevalence of immune-mediated diseases worldwide, including allergic diseases and diabetes mellitus. This has a major impact on the quality of life of many children and adults, as well as representing a substantial burden and cost to the health care system. The hygiene hypothesis proposes that decreased early-life microbial exposure explains the rise in immune-mediated diseases.

  We investigate the association between disruption (e.g. trough antibiotics) of the microbiota and adverse clinical health outcomes (e.g. number of infections or the development eczema and allergies). Furthermore, we are also investigating the effect of the composition of the intestinal microbiome on infant vaccine responses to routine immunisation.

  

  Study protocol for the ABERRANT study: antibiotic-induced disruption of the maternal and infant microbiome and adverse health outcomes – a prospective cohort study among children born at term.
  Volery M, Scherz V, Jakob W, Bandeira D, Deggim-Messmer V, Lauber-Biason A, Wildhaber J, Falquet L, Curtis N, Zimmermann P.
  BMJ Open. 2020