Research presented at Neuroscience 2019, the flagship conference of the Society for Neuroscience, has highlighted research at the intersection of three fascinating areas: neurodevelopment, the immune system and the gut microbiota.
The research, presented by Harvard University Medical Center Associate Professor Jun Huh, reviewed a study published in Nature that suggested specific bacteria present in the gut microbiome of pregnant mother mice could increase the likelihood of behavioral alterations modeling autism spectrum disorder (ASD). Huh went on to illustrate that this link was mediate by immune cells in the mother’s gut.
Th17 cells at the center
Huh’s research began with the observation that mothers who experience inflammation during pregnancy are more likely to have children with ASD. Huh’s research studied a mouse model of maternal inflammation called maternal immune activation (MIA). In MIA, pregnant mother mice are exposed to a virus-mimicking synthetic RNA to produce inflammation. Previous research had highlighted the central role of T helper 17 (Th17) cells, a type of pro-inflammatory immune cell that mobilizes other immune cells against pathogens through the production of cytokines like IL-17, in MIA. In certain autoimmune diseases, such as multiple sclerosis, Th17 cells are thought to play a role in disease pathology. But why MIA specifically activated Th17 cells was still a mystery.
By exposing mother mice to the antibiotic vancomycin to deplete their gut bacteria, Huh’s team was able to stop the behavioral phenotypes of MIA, which include repetitive behaviors, increased anxiety and social deficits, all features shared with ASD in humans.
Huh’s team showed that small filamentous bacteria (SFB) in the gut microbiota were responsible for the promotion of MIA behaviors, and that human gut bacteria known to induce Th17 cells also produced the MIA behaviors.
In their paper’s conclusion, Huh and his colleagues highlight that the findings could have relevance for pregnant women, stating “Women with gut microbial communities that promote excessive TH17 cell differentiation may therefore be more likely to bear children with autistic spectrum disorder in the event of pathological inflammation during pregnancy.”
Session chair Professor Jane Foster, who was not involved with Huh’s research, highlighted the elegance of the study, and its importance to the wider field: “It’s mapping some of that early interaction to mechanisms of “Which T-cells, where?””. Whilst Foster highlighted that methods targeting IL-17 are unlikely to be the next big treatment for a disorder, disentangling IL-17’s contribution is likely to have impact across a lot of other research in the field indirectly.