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Microb Ecol Health Dis. 2015 May 7;26:26878. doi: 10.3402/mehd.v26.26878. eCollection 2015.

Approaches to studying and manipulating the enteric microbiome to improve autism symptoms.

Author information

1
Division of Neurology, Arkansas Children's Hospital Research Institute, Little Rock, AR, USA.
2
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA; REFrye@uams.edu.
3
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
4
Department of Psychology and Psychiatry, Western University, London, ON, Canada.
5
Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada.
6
Department of Surgery, Duke University, Durham, NC USA.
7
N of One: Autism Research Foundation, Dallas, TX, USA.
8
School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, AZ, USA.
9
Swette Center for Environmental Biotechnology, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
10
Private Practice, Benton, AR, USA.
11
Department of Developmental Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
12
National Center for Toxicological Research, Jefferson, AR, USA.
13
MTC, Karolinska Institutet, Stockholm, Sweden.

Abstract

There is a growing body of scientific evidence that the health of the microbiome (the trillions of microbes that inhabit the human host) plays an important role in maintaining the health of the host and that disruptions in the microbiome may play a role in certain disease processes. An increasing number of research studies have provided evidence that the composition of the gut (enteric) microbiome (GM) in at least a subset of individuals with autism spectrum disorder (ASD) deviates from what is usually observed in typically developing individuals. There are several lines of research that suggest that specific changes in the GM could be causative or highly associated with driving core and associated ASD symptoms, pathology, and comorbidities which include gastrointestinal symptoms, although it is also a possibility that these changes, in whole or in part, could be a consequence of underlying pathophysiological features associated with ASD. However, if the GM truly plays a causative role in ASD, then the manipulation of the GM could potentially be leveraged as a therapeutic approach to improve ASD symptoms and/or comorbidities, including gastrointestinal symptoms. One approach to investigating this possibility in greater detail includes a highly controlled clinical trial in which the GM is systematically manipulated to determine its significance in individuals with ASD. To outline the important issues that would be required to design such a study, a group of clinicians, research scientists, and parents of children with ASD participated in an interdisciplinary daylong workshop as an extension of the 1st International Symposium on the Microbiome in Health and Disease with a Special Focus on Autism (www.microbiome-autism.com). The group considered several aspects of designing clinical studies, including clinical trial design, treatments that could potentially be used in a clinical trial, appropriate ASD participants for the clinical trial, behavioral and cognitive assessments, important biomarkers, safety concerns, and ethical considerations. Overall, the group not only felt that this was a promising area of research for the ASD population and a promising avenue for potential treatment but also felt that further basic and translational research was needed to clarify the clinical utility of such treatments and to elucidate possible mechanisms responsible for a clinical response, so that new treatments and approaches may be discovered and/or fostered in the future.

KEYWORDS:

Clostridia; autism spectrum disorder; clinical trials; fecal microbiota transplantation (FMT); gastrointestinal; microbiome; mitochondria; probiotic; short chain fatty acids; vancomycin

PMID:
25956237
PMCID:
PMC4425814

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