Autism GI Pain: New Research Shows Significance

By Teresa Conrick

A newer study caught my eye very recently, Distinct Microbiome-Neuroimmune Signatures Correlate With Functional Abdominal Pain in Children With Autism Spectrum Disorder . It´s a very interesting and important paper as the authors describe – The ability to pinpoint key differences in the mucosal microbiome of these children was in part owing to improvements in technology. Improved sequencing technology and deeper sequencing, particularly in a low-biomass sample such as tissue, enabled the data to be better classified. That is NEW.

Why that´s important is huge as we are able to see that there are specific TYPES of bacteria causing havoc and PAIN for too many children. If we know the enemy, the hope is to stop that pain and improve functioning for that person. Here is their summary (FGID stands for functional gastrointestinal disorders):

In summary, GI phenotypes in ASD are highly variable, and heterogeneity of the autism population can mask significant signals related to GI symptomology. Here, we present distinct microbiome and cytokine measures in the rectal mucosa of children with ASD and confirmed FGIDs compared with neurotypical children both with and without FGIDs. From rectal biopsy specimens obtained during endoscopy, deep molecular analysis of the mucosal microbiome in ASD-FGID showed distinct microbial communities at the predicted species level. Correlations of Clostridiales, including multiple Clostridium species previously associated with ASD, with tryptophan, serotonin, and inflammatory cytokine levels yielded a unique multi-omic profile specific to ASD-FGID and ASD-FGID with abdominal pain. Cytokines indicative of inflammation correlated strongly with several bacteria associated with ASD-FGID, as was the case with tryptophan levels, and these potential associations will be confirmed in future work. These data suggest the presence of a specific microbiome profile in ASD with the identification of organisms previously strongly associated within similar cohorts, albeit in stool-based studies. We advance this concept by showing that these ASD-related organisms interact with the intestinal mucosa and are associated with altered neuroimmune signaling. Although these initial findings are correlative, these data form the framework for future studies targeting tryptophan–serotonin metabolism and inflammatory pathways in FGID in ASD.

Some other highlights:

– A significant increase in several mucosa-associated Clostridiales was observed in ASD-FGID.

– Clostridiales are emerging as major microbial regulators of gut-derived T-cell immune and serotonergic signals that may be associated with ASD

– our identification of clostridial species aligns with those previous autism studies that have identified microbiome alterations. Finegold et al48 originally described increased Clostridium in ASD in 2002

– … multiple organisms in ASD-FGID that correlated significantly with cytokines (interleukin [IL]6, IL1, IL17A, and interferon-γ

– FGIDs encompass a broad range of disorders including functional constipation, nonretentive fecal incontinence, functional abdominal pain, abdominal migraines, and irritable bowel syndrome.

– A common cause of FGIDs is thought to emanate from disturbances to normal communications between the brain and gut…

– Altered microbiome–gut–brain signals also have been reported in ASD, and may contribute independently toward clinical symptoms by changing microbiome composition, tryptophan–serotonin imbalance, and immunologic pathways.

– Bacteria associated with pain in ASD-FGID were identified.

– Correlation of Organisms With Increased Abundance in the ASD Group With Tryptophan or Serotonin

– Cytokine Correlations With Bacteria Significantly Associated With the ASD-FGID Group

– Cytokines Significantly Associated With Abdominal Pain Within the ASD-FGID Group Compared With Groups With No Abdominal Pain

– increased cytokines have been reported in association with a regressive autism phenotype with significant communication challenges and aberrant behaviors. IL6 was highest in the ASD-FGID group, a trend that was exaggerated further in the subset of the ASD-FGID reporting abdominal pain. IL6 also was correlated significantly with 2 Clostridium species (C disporicum and C tertium) that were associated with ASD and abdominal pain.

– IL6 and IL17A are both implicated in the maternal immune activation models that result in autism-like and schizophrenia-like phenotypes in rodents

The take away messages here:

There are SIGNIFICANT bad guy organisms in the gut of those who have an AUTISM diagnosis and the ramifications of this are many. That is NOT new information but it is another BIG nail in the ¨GENES CAUSE¨ coffin. Again, I have said it before and will say it again, that the ¨spectrum of autism¨ may be more of a barometer of the MICROBIOME. A closing thought also is much of the research trying to correlate a mother´s immune activation of these cytokines, especially IL6, may be far off the real trail.

Teresa Conrick is Science Editor for Age of Autism.