ABSTRACT
The importance of alterations in bidirectional communication between gut and brain has become obvious in neuropsychiatric disorders. Gastrointestinal (GI) disturbances are very common in autism spectrum disorders (ASD), and the GI microbiota profiles in children with ASD are significantly different from those in the general population. Fragile X syndrome (FXS) is an inheritable developmental disability in humans, and patients with FXS exhibit autistic behaviors such as mental retardation and impaired social communication or interaction. We hypothesized that an increase in specific gut microbiota by fecal microbiota transplantation (FMT) would mitigate autistic-like behaviors. To test this hypothesis, we measured the effects of FMT from normal mice to Fmr1 KO mice on autistic-like behaviors using several behavioral tests. Because the amounts of A. muciniphila in Fmr1 KO mice was very low, we assessed A. muciniphila population, tested the expression of MUC2, and analyzed goblet cells in the gut after the FMT. We found that FMT ameliorated autistic-like behaviors, especially memory deficits and social withdrawal, and we observed that the levels of A. muciniphila were normalized to wild-type levels. In addition, FMT attenuated the increased levels of TNFα and Iba1 in the brains of Fmr1 KO mice. These results suggest that FMT could be a useful tool for the treatments of cognitive deficits and social withdrawal symptoms observed in FXS or ASD because it increases the population of A. muciniphila and decreases TNFα and Iba1 levels.
Subject(s)
Autistic Disorder/therapy , Fecal Microbiota Transplantation/methods , Fragile X Mental Retardation Protein/genetics , Fragile X Syndrome/therapy , Gastrointestinal Microbiome , Animals , Autistic Disorder/microbiology , Behavior, Animal/physiology , Brain/metabolism , Cognitive Dysfunction/etiology , Cognitive Dysfunction/microbiology , Cognitive Dysfunction/therapy , Disease Models, Animal , Female , Fragile X Syndrome/microbiology , Fragile X Syndrome/psychology , Male , Mice , Mice, Inbred C57BL , Mice, KnockoutABSTRACT
We present data on fragile X expression in lymphocytes obtained from the following patients: a university student, an infertile couple, 6 of 22 prostatic cancer patients, a meningioma patient, and members of families with meningioma and familial gliomas. All patients were of normal intelligence. In addition, we report 3 cases of central nervous system (CNS) tumors in more typical fragile X families. We suggest that the fragile X expression as well as the clinical findings may be caused by a viral (or similar) infection. The virus may require a receptor protein coded by one allele of a gene on the X chromosome.
