(Continuing highlights from recent MAPS pediatric functional medicine conference. Refer back for prior articles from this enlightening conference and stay tuned for future articles on recent autism research findings like this one.)
With the rising prevalence of autistic spectrum disorder pressing itself upon not only the children and their parents, but upon society as a whole, more researchers are digging into both the primary mechanisms and the secondary repercussions of this enigmatic condition. In this paper, researchers attempted to move from the generally accepted fact that children with autism develop more gastrointestinal symptoms to understanding if this symptom difference could be measured with clinical biomarkers. With autism clearly arising from multiple different triggers, they were considering potential leads for understanding secondary effects as well as potential leads for the causes in some children. Their study was relatively small but did demonstrate statistical significance for both a higher rate of GI symptoms in these children and a higher level of fecal calprotectin in their stool.
Fecal calprotectin serves like C-reactive protein in the blood. When levels of either marker are high, we can know that some degree of inflammation is nearby. The chemical itself, comes from the breakdown of neutrophils, a type of immune cell involved in fighting infection, as they fight whatever is triggering a response in the GI tract. Studies have shown that higher levels of calprotectin correlation with microscopic findings on intestinal biopsies, so we know that it can serve as a reliable marker for gut inflammation in various diseases (1,2).
Clinical observations by those caring for children with ASD have long reported a seemingly higher incidence and severity of GI symptoms in these children than healthy comparisons. In the world of research, many studies supported these clinical reports (3,4,5,6) while some did not find significant differences (7,8,9,10). This current study compared reported symptoms between 40 children with ASD between the ages of 3 and 12 years old with 40 age and gender matched controls who did not have ASD. Children with known or suspected genetic syndromes and with diagnosed GI disease like celiac disease were excluded from the trial.
In the study, several noteworthy results deserve review. While some prior studies showed a wide range in the prevalence of GI symptoms in children with ASD, this study used the 6-GI Severity Index (6-GSI) score to find that 33 of the 40 children reported GI symptoms. This scale looked at constipation, diarrhea, loos stool consistency, offensive stool smell, flatulence, and abdominal pain. They did not report what percent of the 40 healthy controls reported symptoms by this scale. Beyond the symptoms, they measured fecal calprotectin in both groups as a marker of inflammation. A higher percentage of children with ASD demonstrated high levels of this marker and the average across the 40 children with ASD was higher than the 40 healthy control’s average. Finally, they compared the severity of the ASD ratings for the children with both the symptom based 6-GSI score and the levels of fecal calprotectin. While they found a statistically significant correlation between the 6-GSI and the severity of ASD, they did not find one between the level of fecal calprotectin and the severity of ASD.
With all of this in mind, the parents of a child with ASD will read this report and ask what they are to do with this information. A functional medicine provider like myself is left to guide our patient’s parents in applying research like this which is not perfectly clear. We can agree with the general consensus that children with ASD suffer more GI symptoms than children without this neurodevelopmental syndrome. We can consider whether these children need a measurement of fecal calprotectin and do often measure this stool marker along with other GI functional markers for dysbiosis, clostridial or yeast overgrowth, leaky gut, or allergic responses. When we find objective evidence of gastrointestinal dysfunction on such testing or suspect it by history, we apply the therapies which we have seen benefit other similar children. While each child we see with ASD is unique in a sense, there are patterns of disease which respond to patterns of children.
As we work to uncover the root causes of our patient’s ASD, we also work in secondary areas like the GI tract to minimize the impact of such contributors to our patient’s health journey. Helping children with ASD achieve their healthier more abundant life takes time and diligence to address a myriad of such contributing factors, but the work is worth it when those children begin to thrive and overcome this label of ASD.
Primary Article:
Galal Azouz, H., El-din Zakaria, N., Fouad Khalil, A., Mohammad Naguib, S., & Khalil, M. (2021). Gastrointestinal manifestations and their relation to faecal calprotectin in children with autism. Gastroenterology Review/Przegląd Gastroenterologiczny, 16(4), 352-357. https://doi.org/10.5114/pg.2021.111420
Secondary Articles:
- Sidler MA, Leach ST, Day AS. Fecal S100A12 and fecal calprotectin as noninvasive markers for inflammatory bowel disease in children. Inflamm Bowel Dis 2008; 14: 359-66.
- Herrera OR, Christensen ML, Helms RA. Calprotectin: clinical applications in pediatrics. J Pediatr Pharmacol Ther 2016; 21: 308-21.
- Karkelis S, Papadaki O, Lykogeorgou M, et al. Fecal calprotectin in autistic children. Paediatr Child Health 2010; 15: 66A.
- de Magistris L, Familiari V, Pascotto A, et al. Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives. J Pediatr Gastroenterol Nutr 2010; 51: 418-24.
- Babinská K, Tomova A, Celusaková H, et al. Fecal calprotectin levels correlate with main domains of the autism diagnostic interview-revised (ADI-R) in a sample of individuals with autism spectrum disorders from Slovakia. Physiol Res 2017; 66 (Suppl 4): S517-22.
- Eduardo UK, Andrea CM, Zulbey RD, et al. Nonspecific gastrointestinal inflammation not associated with enteropathogens in children with Autism Spectrum Disorder. Curr Top in Biochem Res 2017; 18: 103-15.
- Fernell E, Fagerberg UL, Hellstrom PM. No evidence for a clear link between active intestinal inflammation and autism based on analyses of faecal calprotectin and rectal nitric oxide. Acta Paediatr 2007; 96: 1076-9.
- Wos H, Komraus M, Kazek B, et al. Faecal calprotectin in children with autistic spectrum disorders. Arch Dis Child 2008; 93: 215.
- Strati F, Cavalieri D, Albanese D, et al. New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome 2017; 5: 24.
Sanctuary Functional Medicine, under the direction of Dr Eric Potter, IFMCP MD, provides functional medicine services to Nashville, Middle Tennessee and beyond. We frequently treat patients from Kentucky, Alabama, Mississippi, Georgia, Ohio, Indiana, and more... offering the hope of healthier more abundant lives to those with chronic illness.
