ASSOCIATION OF GUT-BRAIN AXIS BIOMARKERS WITH BEHAVIORAL SYMPTOMS IN AUTISM SPECTRUM DISORDER

Abstract

In individuals with autism spectrum disorder (ASD), gastrointestinal issues are the most common comorbidities with a very high incidence rate. This phenomenon precisely confirms the strength of the functional connection of the gut-brain axis—the two-way interaction between the gut and the brain can be intuitively reflected in the population characteristics of this group of patients. In addition to the observable gastrointestinal discomfort, there are two other physiological changes that can be detected through medical examinations, which are also directly related to these common gastrointestinal problems. One is increased intestinal permeability, which simply means that harmful substances that the gut should originally block can more easily pass through the intestinal wall and enter the body; the other is the occurrence of inflammatory reactions in the body. These two physiological indicators are not only linked to the high prevalence of gastrointestinal problems in ASD patients mentioned earlier, but can also be used to reflect the severity of patients' autistic behavioral symptoms.

Research objective: To explore the association between gut-brain axis-related physiological biomarkers (serum zonulin, lipopolysaccharide-binding protein, high sensitivity c-reactive protein) and ASD outcomes.

Research Methods: This study is a cross-sectional study, which included a total of 85 children aged 4 to 12 years with autism spectrum disorder (ASD). All participating children had visited the pediatric neurology clinic in Peshawar, Khyber Pakhtunkhwa. Researchers first collected blood samples from these children, separated the serum, which is the liquid component of blood, and then used enzyme-linked immunosorbent assay to detect the levels of three gut-brain axis-related biomarkers in the children's serum. The first is serum zonulin, which can reflect intestinal permeability, where intestinal permeability refers to whether the intestinal barrier allows substances that should not pass through to seep into the body easily; the second is lipopolysaccharide-binding protein, which can reflect microbial translocation, that is, it can detect whether microorganisms in the intestine have spread to other parts of the body; the third is high-sensitivity C-reactive protein, which can reflect the body's inflammatory state. In addition to collecting blood to test these physiological indicators, researchers also conducted a specialized assessment of the children's behavioral characteristics, using two well-established tools: the Childhood Autism Rating Scale (CARS) and the Aberrant Behavior Checklist (ABC). Finally, to clarify the association between these gut-brain axis biomarkers and the measured behavioral scores, the researchers used two professional statistical methods, namely correlation analysis and multiple regression models, to test the relationship between the two sets of data.

Results: A positive statistically significant correlation was observed between serum level of Gut permeability biomarker serum zonulin (r=0.58), Microbial translocation biomarker lipopolysaccharide binding protein (r=0.49), and inflammation biomarker high sensitivity c-reactive protein (r=0.38) with the total CARS scores.

Conclusion: Significant correlation was also observed with the irritability sub-score of ABC. In the multiple regression analysis, the best independent predictor was serum zonulin ( =0.41) which explains 42.4% of the total variance in autism severity scores. Conclusion: Elevated levels of biomarkers of increased intestinal permeability, bacterial translocation and inflammation (serum zonulin, lipopolysaccharide binding protein and high sensitive c-reactive protein) are associated with severity of symptoms in paediatric ASD.