Consequences of maternal breast milk antibodies on neonatal mucosal immunity and intestinal microbe composition

Abstract

Abstract Breastfeeding is associated with decreased risk of acquiring inflammatory bowel disorders later in life. As breastfeeding is not possible for all mothers and children, having a mechanistic understanding of this process can lead to the development of early-life interventions to foster beneficial host-microbiota relationships, particularly in neonates who are not breastfed. We have shown that mice lacking breast milk antibodies (bmAbs) exhibit dysregulated intestinal homeostasis. These mice harbor increased numbers of live bacteria in the mesenteric lymph nodes and exhibit perturbations in mucosal immunity, including elevated T follicular helper (Tfh) cell and germinal center (GC) B cell responses in the gut-associated lymphoid tissues. Antibodies are key regulators of host-microbiome interactions, and T-dependent (TD) GC derived B cells can persist up to the lifetime of the host. We hypothesize that the TD antibodies generated by the neonate in the absence of bmAbs target resident gut bacteria and lead to long-term alterations in the composition of the microbiota. We performed RT-PCR of the bacterial 16s rRNA gene to quantify the amount of wall-associated microbes in the small and large intestine of mice that received or did not receive bmAbs. To probe the effects of Tfh cells and TD antibodies, we treated half of the mice from each group with anti-ICOS ligand antibody, which blocks Tfh and GC cell formation. We found no significant difference in bacterial burden across all four groups in the small or large intestine. These data suggest that Tfh-cell dependent, bmAb-dependent antibodies do not alter the abundance of wall-associated microbes. Studies are ongoing to determine if bmAbs affect intestinal microbe composition later in life.