Preconception Helminth Infection Alters Offspring Microbiota and Immune Subsets in a Mouse Model

Both maternal microbiota and helminth infection may alter offspring immunity but the relationship between these is underexplored. We hypothesized that maternal helminth exposure prior to pregnancy has lasting consequences on offspring intestinal microbiota and consequent immunity. Female BALB/c adult mice were infected with 500L3 Nippostrongylus brasiliensis (N brasiliensis). Infection was cleared by ivermectin treatment, and mice were mated 3 weeks post-infection (NbM). Control mice were not infected but were exposed to ivermectin (NvM). We analysed maternal gut microbiota during pregnancy, breastmilk microbiota and offspring faecal microbiota and immunity 2 weeks after delivery. During pregnancy, NbM (Mothers previously infected with Nippostrongylus brasiliensis) displayed significantly altered stool bacterial communities (R  = .242; P = .001), with increased abundance of Enterococcaceae versus NvM (Naive mothers). Similarly, we observed a profound impact on breastmilk microbiota in NbM vs NvM. Moreover, NbM pups showed significantly altered gut microbial communities at 14 days of age versus those born to NvM with increased relative abundance of Coriobacteriaceae and Micrococcaceae. These changes were associated with alterations in pup immunity including increased frequencies and numbers of activated CD4 T cells (CD4 + CD44hi) in NbM offspring spleens. Taken together, we show that preconception helminth infections impact offspring immunity possibly through alteration of maternal and offspring microbiota.