Autism In Mice Linked To Maternal Microbiome

Kim et al., 2017, “Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring”, Nature

Summarized from DalMUG group discussion and written by: Emily Lamoureux

Summary

It has been shown in several animal models that activation of the maternal immune system (MIA), such as by viral infection, is associated with the development of neurological disorders in offspring. Epidemiological studies in humans have also suggested that maternal viral infection is associated with an increase in autism spectrum disorder (ASD). Earlier studies in mice have demonstrated a role for interleukin-17 (IL-17) in ASD-like phenotypes and abnormal cortical development. Here, Gloria Choi, Jun Huh and colleagues provide evidence that MIA-mediated abnormal behavioural phenotypes requires both the presence of segmented filamentous bacteria (SBF) and viral immune activation during pregnancy in mice. These two factors induce the differentiation of IL-17-producing T helper 17 (TH17) cells in pregnant mothers. Their offspring display behavioural abnormalities, which are associated with the presence of cortical patches in the somatosensory cortex of the brain. Overall, we thought this was a thorough analysis of a the interactions between gut microbiota and the host immune system in an interesting ASD mouse model.

Points of Interest

  • Consistent results across experiments: presence of MIA and segmented filamentous bacteria in dams are always associated with an increase in abnormal behaviours in offspring. These abnormal behaviours were consistently reduced when dams were treated with antibiotics

  • ASD in mouse offspring requires both maternal inflammation as well as segmented filamentous bacteria during pregnancy: demonstrated by cross-fostering studies after birth where ASD phenotype is not transferred from SFB-enriched mothers to mice that were birthed by SFB-negative mothers (Nature not nurture)

  • Described pathway behind immune activation from dsRNA in dams: poly(I:C) primes CD11c+ dendritic cells, which then stimulated CD4+T cells to produce IL-17 and subsequent inflammation in mothers

Points of Confusion

  • Maternal immune activation in mice as a model for ASD: No tests for learning which is an important part of the ASD phenotype

  • Th-17 bacteria given to mice were isolated from UC patient (already primed for inflammation?)

  • Did not profile whole microbiome using 16S or metagenomic sequencing – Jackson vs Taconic mice

  • Researchers did not profile the immune markers or the microbiome in offspring

Written on November 15, 2017