title: Towards large-cohort comparative studies to define the factors influencing the gut microbial community structure of ASD patients.
abstract: Differences in the gut microbiota have been reported between individuals with autism spectrum disorders (ASD) and neurotypical controls, although direct evidence that changes in the microbiome contribute to causing ASD has been scarce to date. Here we summarize some considerations of experimental design that can help untangle causality in this complex system. In particular, large cross-sectional studies that can factor out important variables such as diet, prospective longitudinal studies that remove some of the influence of interpersonal variation in the microbiome (which is generally high, especially in children), and studies transferring microbial communities into germ-free mice may be especially useful. Controlling for the effects of technical variables, which have complicated efforts to combine existing studies, is critical when biological effect sizes are small. Large citizen-science studies with thousands of participants such as the American Gut Project have been effective at uncovering subtle microbiome effects in self-collected samples and with self-reported diet and behavior data, and may provide a useful complement to other types of traditionally funded and conducted studies in the case of ASD, especially in the hypothesis generation phase.
authors.affiliation: BioFrontiers Institute, University of Colorado, Boulder, CO, USA.|Department of Computer Science, University of Colorado, Boulder, CO, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: McDonald
authors.affiliation: Center for Infection and Immunity, Columbia University Mailman School of Public Health, New York, NY, USA.|Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA.
authors.forename: Mady
authors.initials: M
authors.lastname: Hornig
authors.affiliation: Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lozupone
authors.affiliation: Department of Computer Science, University of Colorado, Boulder, CO, USA.|Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, CO, USA.
authors.forename: Justine
authors.initials: J
authors.lastname: Debelius
authors.affiliation: Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne, IL, USA.|Department of Ecology and Evolution, University of Chicago, Chicago, IL, USA.|Marine Biological Laboratory, Woods Hole, MA, USA.|College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, China; gilbertjack@anl.gov.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Gilbert
authors.affiliation: Department of Computer Science, University of Colorado, Boulder, CO, USA.|Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, CO, USA.|Howard Hughes Medical Institute, Boulder, CO, USA.
authors.forename: Rob
authors.initials: R
authors.lastname: Knight
keywords: autism; microbiology; microbiome; neurological