Our intestine is colonized by a myriad of symbiotic microbes that constitute the intestinal microbiota. They feed on the nutrients that we ingest but also help us extract energy from food and stimulate our immune system. While babies are delivered from a sterile womb, they are exposed to microbes after birth. The newborn microbiota is still simple and consists of species adapted to metabolize sugars from breast milk. With the introduction of solid food, the gut microbiota matures and becomes more diverse. Disturbance of the microbiota is associated to many immune-mediated diseases such as inflammatory bowel disease.
Research from the last decade had elucidated that there is a narrow time window after birth, during which the immune system is sensitive to cues from the environment, especially the microbiota. It was shown that germ-free (GF) mice that lack a microbiota entirely are more prone to allergy. Colonization of GF mice during early life can prevent later life allergy while colonization in adult age fails to do so.
Our lab had previously shown that this ‘window-of-opportunity’ does not only open at birth but already during pregnancy. Metabolites from the maternal microbiota are transported to the offspring through the placenta and breast milk and stimulate the baby’s innate immune system and gut function (Gomez de Agüero & Ganal-Vonarburg et al., Science, 2016). This study was enabled by a model of gestational colonization: Pregnant dams are intestinally exposed to the E. coli strain HA107 which cannot replicate in vivo and is thus cleared from otherwise GF mice. Consequently, the mother is exposed to microbes in her intestine during pregnancy but returns GF before delivery thereby also preventing any direct microbial exposure of the pups.
In the context of the MEMORIS project (Maternal Enteric Microbiota for Offspring Repertoire development and Illness Susceptibility), we wished to address how these gestational cues influence the offspring as they become colonized with their own microbiota as is the case under physiological conditions. More specifically, our aims were to understand the consequences of maternal microbiota cues for (1) the pups’ own microbiota development, (2) their adaptive immune system and (3) disease susceptibility.
