The microbiota shapes the development of the mouse hypothalamic paraventricular nucleus

Microbes massively colonize the mammalian newborn at birth. We previously reported that the microbiota influences key neurodevelopmental events, e.g., when compared to their conventionally colonized (CC) counterparts, sterile newborn mice (“germ-free” or GF) show higher cell death in the hypothalamic paraventricular nucleus (PVN). Here, we tested the hypothesis that the microbiota, perhaps via cell death mechanisms, shapes PVN development. To this aim, we used a cross-fostering approach that also allowed us to test whether any potential effects are influenced by microbial colonization at birth or programmed prenatally via the maternal microbiota. Specifically, we cross-fostered GF pups to CC dams (GF → CC) immediately after birth and compared them to control groups cross-fostered within microbial status (CC → CC, GF → GF). At postnatal day 7, GF → GF and GF → CC newborns had fewer PVN cells than did CC → CC newborns, without affecting PVN volume. In a follow-up experiment, we confirmed a reduction in PVN cell number with no change in PVN volume in adult GF mice. Thus, the greater cell death previously observed in the PVN of newborn GF mice is associated with a permanent reduction in cell number. Because the deficit is not altered by introducing a microbiota at birth, our findings also suggest that the maternal microbiota shapes development of the PVN starting in utero.