Metabolic network analysis of pre-ASD newborns and 5-year-old children with autism spectrum disorder, 2024, Lingampelly, Naviaux et al.

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SNT Gatchaman

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Metabolic network analysis of pre-ASD newborns and 5-year-old children with autism spectrum disorder
Lingampelly, Sai Sachin; Naviaux, Jane C.; Heuer, Luke S.; Monk, Jonathan M.; Li, Kefeng; Wang, Lin; Haapanen, Lori; Kelland, Chelsea A.; Van de Water, Judy; Naviaux, Robert K.

Classical metabolomic and new metabolic network methods were used to study the developmental features of autism spectrum disorder (ASD) in newborns (n = 205) and 5-year-old children (n = 53).

Eighty percent of the metabolic impact in ASD was caused by 14 shared biochemical pathways that led to decreased anti-inflammatory and antioxidant defenses, and to increased physiologic stress molecules like lactate, glycerol, cholesterol, and ceramides. CIRCOS plots and a new metabolic _ network parameter, V net , revealed differences in both the kind and degree of network connectivity. Of 50 biochemical pathways and 450 polar and lipid metabolites examined, the developmental regulation of the purine network was most changed. Purine network hub analysis revealed a 17-fold reversal in typically developing children. This purine network reversal did not occur in ASD.

These results revealed previously unknown metabolic phenotypes, identified new developmental states of the metabolic correlation network, and underscored the role of mitochondrial functional changes, purine metabolism, and purinergic signaling in autism spectrum disorder.

Link | PDF (Nature Communications Biology) [Open Access]
 
Medical Xpress: Metabolism of autism reveals developmental origins

"At birth, the physical appearance and behavior of a child who will develop autism over the next few years are indistinguishable from that of a neurotypical child. Indeed, in most cases the fate of the child with regard to autism is not set at birth," said Robert Naviaux, M.D., Ph.D., professor in the Departments of Medicine, Pediatrics and Pathology at UC San Diego School of Medicine.
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When comparing the metabolic profiles of children in the cohort who were eventually diagnosed with autism to those who developed neurotypically, they found striking differences. Of the 50 different biochemical pathways the researchers investigated, just 14 were responsible for 80% of the metabolic impact of autism.

The pathways that were most changed are related to the cell danger response, a natural and universal cellular reaction to injury or metabolic stress. The body has biochemical safeguards in place that can shut down the cell danger response once the threat has passed, and Naviaux hypothesizes that autism occurs when these safeguards fail to develop normally. The result is heightened sensitivity to environmental stimuli, and this effect contributes to sensory sensitivities and other symptoms associated with autism.
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"Metabolism is the language that the brain, gut and immune system use to communicate, and autism occurs when the communication between these systems is changed," added Naviaux.

The cell danger response is primarily regulated by adenosine triphosphate (ATP) the body's chemical energy currency. While these ATP-signaling pathways do not develop normally in autism, they may be partially restorable with existing pharmaceutical drugs. In 2017, Naviaux and his team completed early clinical testing for suramin, the only drug approved in humans that can target ATP signaling and which is normally used to treat African sleeping sickness.
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A major result of this research was that the developmental differences observed in ASD were not the result of an increase or decrease of one causal metabolite, or an isolated change in the gut-brain axis, or neuroendocrine, autonomic, cytokine, or immunologic circuits. Instead, it was the interconnectedness and developmental state of the metabolic network that underlies all these systems that was fundamentally changed.
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The implication of this finding is that the metabolic changes found in children with ASD were not the result of cell dysfunction or damage. Instead, the measured changes were the result of normal physiologic and neurodevelopmental responses to metabolic signals that cells received in ASD that were not being sent in typically developing children.
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If I may ask and making no comment on this research itself…

Whether or not Autism and ME are in some way connected which some have proposed in highly implausible and wildly damaging ways (consumed any bleach recently anyone?). Others relatively innocuously so, look at us all on here geeking out over our special interests huh! ;)
Putting this aside for now as irrelevant to the following question.

Might this type of finding of multiple interactions making up a particular outcome explain why our perhaps rather unimaginative less cutting edge research and medical professionals have been so sure that we’re imagining so hard that we’re creating physical symptoms, because nothing as far as they can see is wrong with our physical structures and they can’t imagine cumulative effects of chemicals causing illness but not structural damage that they can easily detect?

I don’t know if these findings are correct or valid, but I assume things like this can and do occur within the chemistry of the living human body and that this affects peoples experience in life and their physical health. So could plausibly be us too no?
 
Ash said:
If I may ask and making no comment on this research itself…

Whether or not Autism and ME are in some way connected which some have proposed in highly implausible and wildly damaging ways (consumed any bleach recently anyone?). Others relatively innocuously so, look at us all on here geeking out over our special interests huh! ;)
Putting this aside for now as irrelevant to the following question.

Might this type of finding of multiple interactions making up a particular outcome explain why our perhaps rather unimaginative less cutting edge research and medical professionals have been so sure that we’re imagining so hard that we’re creating physical symptoms, because nothing as far as they can see is wrong with our physical structures and they can’t imagine cumulative effects of chemicals causing illness but not structural damage that they can easily detect?

I don’t know if these findings are correct or valid, but I assume things like this can and do occur within the chemistry of the living human body and that this affects peoples experience in life and their physical health. So could plausibly be us too no?
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This is why I find the Precision Life research interesting, it's a look at symptoms and genes on pathways and how they relate .
The interconnectedness. It's a systems approach.
As I've said on more than one occasion we need an interested climate change scientist on board .
 
Ash said:
because nothing as far as they can see is wrong with our physical structures and they can’t imagine cumulative effects of chemicals causing illness but not structural damage that they can easily detect?
Click to expand...
Dealing with this in our understanding has been my dominant thinking for years. Shifts in biochemical regulation are potentially as damaging as gross structural changes. I have been calling these biochemical lesions. Of course I have my own biases being a biochemist trained in systems theory.
 
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