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A model for the induction of autism in the ecosystem of the human body: the anatomy of a modern pandemic?

Bilbo SD, Nevison CD, Parker W - Microb. Ecol. Health Dis. (2015)

Bottom Line: Others are convinced that the disease is not pandemic in nature, but rather that it has been with humanity for millennia, with its biological and neurological underpinnings just now being understood.Finally, the potential role of the microbial flora (the microbiome) in the pathogenesis of autism is discussed, with the view that the microbial flora is a subset of the life associated with the human body, and that the entire human biome, including both the microbial flora and the fauna, has been radically destabilized by modern culture.It is suggested that the unequivocal way to resolve the debate regarding the pandemic nature of autism is to perform an experiment: monitor the prevalence of autism after normalizing immune function in a Western population using readily available approaches that address the well-known factors underlying the immune dysfunction in that population.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology & Neuroscience, Systems & Integrative Neuroscience Group, Duke University, Durham, NC, USA.

ABSTRACT

Background: The field of autism research is currently divided based on a fundamental question regarding the nature of autism: Some are convinced that autism is a pandemic of modern culture, with environmental factors at the roots. Others are convinced that the disease is not pandemic in nature, but rather that it has been with humanity for millennia, with its biological and neurological underpinnings just now being understood.

Objective: In this review, two lines of reasoning are examined which suggest that autism is indeed a pandemic of modern culture. First, given the widely appreciated derailment of immune function by modern culture, evidence that autism is strongly associated with aberrant immune function is examined. Second, evidence is reviewed indicating that autism is associated with 'triggers' that are, for the most part, a construct of modern culture. In light of this reasoning, current epidemiological evidence regarding the incidence of autism, including the role of changing awareness and diagnostic criteria, is examined. Finally, the potential role of the microbial flora (the microbiome) in the pathogenesis of autism is discussed, with the view that the microbial flora is a subset of the life associated with the human body, and that the entire human biome, including both the microbial flora and the fauna, has been radically destabilized by modern culture.

Conclusions: It is suggested that the unequivocal way to resolve the debate regarding the pandemic nature of autism is to perform an experiment: monitor the prevalence of autism after normalizing immune function in a Western population using readily available approaches that address the well-known factors underlying the immune dysfunction in that population.

No MeSH data available.


Related in: MedlinePlus

A model for the induction of autism, with a central focus on glutathione metabolism. Induction of autism occurs along pathways that strongly resemble those seen in allergy, autoimmune disease, and cancer. Indeed, this diagram is similar to that proposed by others for the induction of autism (49), with the exception of the emphasis on the biome. Autism, in particular, apparently involves oxidative stress at an early age of development. Although the glutathione pathway is emphasized in this diagram, other pathways involved with oxidative stress, including the cP450 system (50, 51), are probably also involved in pathology under the influence of chronic inflammation. This model provides at least two means by which the microbiome might be involved in the induction of autism: (a) alteration of the microbiome could destabilize the ecosystem of the human body, leading to a much greater propensity for inflammatory reactions, and (b) aberrant interactions between the microbiome and the immune system could lead to increased inflammation and oxidative stress, with metabolic dysfunction via glutathione insufficiency or cP450 system downregulation (50, 51) exacerbating the problem. Thus, the microbiome could be involved in more distal and more proximal aspects of autism induction, respectively.
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Figure 0003: A model for the induction of autism, with a central focus on glutathione metabolism. Induction of autism occurs along pathways that strongly resemble those seen in allergy, autoimmune disease, and cancer. Indeed, this diagram is similar to that proposed by others for the induction of autism (49), with the exception of the emphasis on the biome. Autism, in particular, apparently involves oxidative stress at an early age of development. Although the glutathione pathway is emphasized in this diagram, other pathways involved with oxidative stress, including the cP450 system (50, 51), are probably also involved in pathology under the influence of chronic inflammation. This model provides at least two means by which the microbiome might be involved in the induction of autism: (a) alteration of the microbiome could destabilize the ecosystem of the human body, leading to a much greater propensity for inflammatory reactions, and (b) aberrant interactions between the microbiome and the immune system could lead to increased inflammation and oxidative stress, with metabolic dysfunction via glutathione insufficiency or cP450 system downregulation (50, 51) exacerbating the problem. Thus, the microbiome could be involved in more distal and more proximal aspects of autism induction, respectively.

Mentions: The proposed mechanism by which acetaminophen triggers autism involves depletion of glutathione, a critical factor that moderates the impact of oxidative stress. With this idea in view, the connections between immune instability, oxidative stress, and autism come into focus (Fig. 3). In this model, immune system destabilization by environmental factors interacts with oxidative stressors, causing inflammation that, under the appropriate conditions, can lead to autism (Fig. 3). In this model, a potential role of the microbial flora as a source of oxidative stress during the pathogenesis of autism becomes evident. Other information regarding the cause of autism also falls into place given the view presented in Fig. 3. For example, the gender bias associated with autism is understandable given the observations that testosterone ‘depresses resistance to oxidative stress’ in an animal model (52) and may be deleterious for brain function under conditions of high oxidative stress in humans (53). Further, the association between autism and use of the drug valproic acid (54), which causes microglia activation in cultured glial cells (55), is also consistent with the view presented in Fig. 3.


A model for the induction of autism in the ecosystem of the human body: the anatomy of a modern pandemic?

Bilbo SD, Nevison CD, Parker W - Microb. Ecol. Health Dis. (2015)

A model for the induction of autism, with a central focus on glutathione metabolism. Induction of autism occurs along pathways that strongly resemble those seen in allergy, autoimmune disease, and cancer. Indeed, this diagram is similar to that proposed by others for the induction of autism (49), with the exception of the emphasis on the biome. Autism, in particular, apparently involves oxidative stress at an early age of development. Although the glutathione pathway is emphasized in this diagram, other pathways involved with oxidative stress, including the cP450 system (50, 51), are probably also involved in pathology under the influence of chronic inflammation. This model provides at least two means by which the microbiome might be involved in the induction of autism: (a) alteration of the microbiome could destabilize the ecosystem of the human body, leading to a much greater propensity for inflammatory reactions, and (b) aberrant interactions between the microbiome and the immune system could lead to increased inflammation and oxidative stress, with metabolic dysfunction via glutathione insufficiency or cP450 system downregulation (50, 51) exacerbating the problem. Thus, the microbiome could be involved in more distal and more proximal aspects of autism induction, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4310853&req=5

Figure 0003: A model for the induction of autism, with a central focus on glutathione metabolism. Induction of autism occurs along pathways that strongly resemble those seen in allergy, autoimmune disease, and cancer. Indeed, this diagram is similar to that proposed by others for the induction of autism (49), with the exception of the emphasis on the biome. Autism, in particular, apparently involves oxidative stress at an early age of development. Although the glutathione pathway is emphasized in this diagram, other pathways involved with oxidative stress, including the cP450 system (50, 51), are probably also involved in pathology under the influence of chronic inflammation. This model provides at least two means by which the microbiome might be involved in the induction of autism: (a) alteration of the microbiome could destabilize the ecosystem of the human body, leading to a much greater propensity for inflammatory reactions, and (b) aberrant interactions between the microbiome and the immune system could lead to increased inflammation and oxidative stress, with metabolic dysfunction via glutathione insufficiency or cP450 system downregulation (50, 51) exacerbating the problem. Thus, the microbiome could be involved in more distal and more proximal aspects of autism induction, respectively.
Mentions: The proposed mechanism by which acetaminophen triggers autism involves depletion of glutathione, a critical factor that moderates the impact of oxidative stress. With this idea in view, the connections between immune instability, oxidative stress, and autism come into focus (Fig. 3). In this model, immune system destabilization by environmental factors interacts with oxidative stressors, causing inflammation that, under the appropriate conditions, can lead to autism (Fig. 3). In this model, a potential role of the microbial flora as a source of oxidative stress during the pathogenesis of autism becomes evident. Other information regarding the cause of autism also falls into place given the view presented in Fig. 3. For example, the gender bias associated with autism is understandable given the observations that testosterone ‘depresses resistance to oxidative stress’ in an animal model (52) and may be deleterious for brain function under conditions of high oxidative stress in humans (53). Further, the association between autism and use of the drug valproic acid (54), which causes microglia activation in cultured glial cells (55), is also consistent with the view presented in Fig. 3.

Bottom Line: Others are convinced that the disease is not pandemic in nature, but rather that it has been with humanity for millennia, with its biological and neurological underpinnings just now being understood.Finally, the potential role of the microbial flora (the microbiome) in the pathogenesis of autism is discussed, with the view that the microbial flora is a subset of the life associated with the human body, and that the entire human biome, including both the microbial flora and the fauna, has been radically destabilized by modern culture.It is suggested that the unequivocal way to resolve the debate regarding the pandemic nature of autism is to perform an experiment: monitor the prevalence of autism after normalizing immune function in a Western population using readily available approaches that address the well-known factors underlying the immune dysfunction in that population.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology & Neuroscience, Systems & Integrative Neuroscience Group, Duke University, Durham, NC, USA.

ABSTRACT

Background: The field of autism research is currently divided based on a fundamental question regarding the nature of autism: Some are convinced that autism is a pandemic of modern culture, with environmental factors at the roots. Others are convinced that the disease is not pandemic in nature, but rather that it has been with humanity for millennia, with its biological and neurological underpinnings just now being understood.

Objective: In this review, two lines of reasoning are examined which suggest that autism is indeed a pandemic of modern culture. First, given the widely appreciated derailment of immune function by modern culture, evidence that autism is strongly associated with aberrant immune function is examined. Second, evidence is reviewed indicating that autism is associated with 'triggers' that are, for the most part, a construct of modern culture. In light of this reasoning, current epidemiological evidence regarding the incidence of autism, including the role of changing awareness and diagnostic criteria, is examined. Finally, the potential role of the microbial flora (the microbiome) in the pathogenesis of autism is discussed, with the view that the microbial flora is a subset of the life associated with the human body, and that the entire human biome, including both the microbial flora and the fauna, has been radically destabilized by modern culture.

Conclusions: It is suggested that the unequivocal way to resolve the debate regarding the pandemic nature of autism is to perform an experiment: monitor the prevalence of autism after normalizing immune function in a Western population using readily available approaches that address the well-known factors underlying the immune dysfunction in that population.

No MeSH data available.


Related in: MedlinePlus