Introduction.

A utism spectrum disorder (ASD) is a devastating neurodevelopmental disorder currently estimated to affect 1 in 68 individuals in the United States (1). The biological underpinnings of ASD are unclear at this time. Although research has concentrated on genetics (2), single gene defects and chromosomal abnormalities only account for a minority of ASD cases (3). An increasing number of research studies support evidence for underlying physiological disturbances, including mitochondrial dysfunction, immune dysregulation, and oxidative stress (2, 4, 5), which may be pathophysiological hallmarks of a very complex disease process that contribute, at least in part, to medical comorbidities associated with ASD as well as core and associated ASD symptoms. Furthermore, it is becoming clear that the internal environment of affected individuals as well as disturbances from the external environment (e.g. biome, diet, toxicants) play a significant role in the development of ASD, although the exact mechanisms behind these influences and how they contribute to a complex phenotypic expression of ASD is unclear at this time (2, 6). To this end, it is essential to have a broad consideration of factors that could cause and/or contribute to the development of ASD. One interesting aspect of ASD, and perhaps a clue to the putative etiological factors at play, is the medical conditions associated with ASD. One of the most prevalent reported medical conditions is gastrointestinal (GI) disorders (7). Not only are GI symptoms very prevalent, but many parents report significant improvements with change in diet. Parallel to the increasing awareness of the GI system and diet in relation to ASD, the general scientific and medical communities have been recognizing that the trillions of microbes that inhabit the human digestive tract, the so-called enteric microbiome, may influence host physiology, including the immune system and metabolism (8, 9), and may play a major role in modulating normal brain development as well as directly modulating behavior (10 12). This has resulted in studies more closely investigating the possible involvement of the enteric microbiome in ASD (13, 14). To accelerate the dissemination of knowledge, a worldwide collaboration between leaders in this field was held on Thursday, June 26, 2014 at the 1st International Symposium on the Microbiome in Health and Disease with a Special Focus on Autism (www.microbiome-autism. com). The symposium included clinicians, research scientists, and parents of children with ASD (See Table 1). Important highlights from the symposium are documented within seven manuscripts in this special issue of Microbial Ecology in Health and Disease along with this introduction and concluding remarks by Dr. Tore Midtvedt, the editor-in-chief of the journal. Two papers provide interesting perspectives on the microbiome with respect to health and disease, particularly commenting on how the microbiome may have changed because of self-imposed societal changes in environmental exposures and diet. Drs Toh and Allen-Vercoe provide a nice introduction to the microbiome and the recent realization of its importance and then comment on common changes in medicine and lifestyles which may lead to a decrease in microbial diversity, potentially leading to chronic disease such as ASD (15). Drs Bilbo, Nevison, and Parker then point out how the microbial flora as well as the fauna have changed because of modern Western culture, possibly leading to a rise in immune dysregulation and autoimmune disease, particularly commenting on the ‘Biome Depletion’ theory of immune disease (16). They nicely point out the connections with ASD through immune abnormalities associated with ASD. Three papers more directly address the relationship between the microbiome and ASD. A group of leaders in the microbiota changes association with ASD from Arizona State University provide an excellent summary of the research connecting ASD with GI disorders and changes in the enteric microbiome (13). They provide unique and original data supporting the notion that the Western diet has resulted in a shift in the microbiome composition. In another review article, leaders in the field of abnormalities in mitochondrial function and propionic acid in relation to ASD discuss the significance of mitochondrial disorders in ASD with respect to GI symptoms and how enteric bacteria may induce or