The Korean news media has been busy reporting two papers published in Nature last month by Harvard Medical School professor Huh Jun-ryeol and MIT professor Gloria Choi. The coverage has attracted massive attention from the general public, researchers, clinicians, and the parents of children with autism.
Because of the way the media is framing the research, much of Korea has come to believe that maternal infection during pregnancy is a major cause of autism. Many mothers with autistic children now blame themselves for their children’s conditions. And most people assume that a cure or prevention for autism are now around the corner.
But the Korean reporting contains many misunderstandings. Indeed, the international Autism Science Foundation went as far as calling out one English language article for its misleading title (“Korean-American Professor Couple Identify Major Cause of Autism”) and overstated findings. I’d like to briefly address some of the misconceptions.
It has long been thought that infection during pregnancy and subsequent maternal immune activation (MIA) may contribute to the pathogenesis of autism.
Indeed, Huh and Choi have made previous contributions to our understanding of this pathway. In a 2016 paper published in Science, they showed that a kind of immune (T helper 17, Th17) cell and an immune protein (interleukin-17a) in mothers play a significant role in producing brain abnormalities in mouse fetuses and behavioral abnormalities in mouse offspring.
On September 13, 2017, in their two Nature papers, Huh and Choi simply went further. The first paper showed that maternal gut bacteria promote Th17 cell differentiation, induce MIA, and increase the risk of neurodevelopmental disorders in offspring in mice. The second showed that MIA-related brain abnormalities tend to localize to a particular region of the primary somatosensory cortex in mice. In that region, the activity of certain neurons was associated with social deficits, while the activity of some other neurons was associated with a repetitive behavior. (Social deficits and repetitive behavior are both common in autism.)
So Huh and Choi’s research sheds light on how maternal infection during pregnancy can contribute to developmental disorders in children. It also provides some insight on the role of the brain-gut axis in the pathogenesis of autism. However, there are several points to bear in mind when reading their papers.
First, there have been previous reports of maternal infection during pregnancy being related to neurodevelopmental disorders in offspring. However, the degree of association with autism reported in large population studies was not very high (odds ratios of 1.3–2), especially compared to those of known genetic variants (odds ratios of 10–30). So we should view maternal infection during pregnancy as one of many causes of autism, not a major cause.
Second, it is almost impossible to not experience any viral or bacterial infection during the nine months of pregnancy, and not all kids whose mothers have infections during pregnancy develop neurodevelopmental disorders like autism. We therefore need to consider other maternal or fetal factors that modulate the link between maternal infection and immune activation and later neurodevelopmental disorders in offspring. The importance of Huh and Choi’s studies lies in the understanding they bring to the possible role of gut bacteria in all this. But there could be other causes at play. Genetic factors, for instance.
Third, we can never directly extrapolate from findings with mice. Moreover, the mouse brain areas found in this study are quite different from those reported in human studies. The mouse brain does not have a higher association cortex, which is implicated in autism. And while the behavioral assays used in their studies—ultrasonic vocalizations, the three-chamber social approach, the marble burying test, and the open field test—are the most widely-used tests in autism mouse studies, they are still different from the behavioral symptoms of autism.
Fourth, these new studies imply that treatment with T-cell differentiating gut bacteria before pregnancy could be helpful in preventing autism. But these studies are the very first to indicate a possible role of gut bacteria and related maternal immune activation in the development of autism. We need more evidence and many human trials to be able to recommend gut bacteria treatment before pregnacy. Furthermore, this study has no bearing on the treatment of autism itself.
Despite these caveats, I believe Huh and Choi have made an immense contribution to our understanding of the link between the immune system and gut bacteria, and the possible pathogenesis of autism.
However, the Korean media companies that are overstating the results and confusing the public need to rethink their reporting. Journalistic exaggeration could hurt the parents and families of children with autism and hinder communication between scientists and the public.
Choi GB, Yim YS, Wong H, Kim S, Kim H, Kim SV, Hoeffer CA, Littman DR, Huh JR. The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring. Science. 2016;351:933-9.
Kim S, Kim H, Yim YS, Ha S, Atarashi K, Tan TG, Longman RS, Honda K, Littman DR, Choi GB, Huh JR. Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring. Nature. 2017;549:528-532.
Shin Yim Y, Park A, Berrios J, Lafourcade M, Pascual LM, Soares N, Yeon Kim J, Kim S, Kim H, Waisman A, Littman DR, Wickersham IR, Harnett MT, Huh JR, Choi GB. Reversing behavioural abnormalities in mice exposed to maternal inflammation. Nature. 2017;549:482-487.
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