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Preconception helminth infection alters offspring microbiota and immune subsets in a mouse model.

AIMS
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.


METHODS
Female BALB/c adult mice were infected with 500L3 Nippostrongylus brasiliensis (N.b). Infection was cleared by Ivermectin treatment and mice mated three weeks post infection (NbM). Control mice were not infected but were exposed to Ivermectin (NvM). We analyzed maternal gut microbiota during pregnancy, breastmilk microbiota as well as offspring fecal microbiota and immunity two weeks after delivery.


RESULTS
During pregnancy, NbM displayed significantly altered stool bacterial communities (R2=0.242; p=0.001), with increased abundance of Enterococcaceae versus NvM. 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.


CONCLUSIONS
Taken together, we show that preconception helminth infections impact offspring immunity possibly through alteration of maternal and offspring microbiota.