Gastrointestinal pathology in childhood disorders of learning, behavior and development

Can gastrointestinal pathology be a contributing factor in neurodevelopmental disorders? Consider this study published in the American Journal of Gastroenterology in which the authors begin:

"Intestinal pathology, i.e., ileocolonic lymphoid nodular hyperplasia (LNH) and mucosal inflammation, has been described in children with developmental disorders. This study describes some of the endoscopic and pathological characteristics in a group of children with developmental disorders (affected children) that are associated with behavioral regression and bowel symptoms, and compares them with pediatric controls."

They performed ileocolonoscopies and biopsies on 60 children whose diagnoses included Developmental diagnoses were autism (50 patients), Asperger's syndrome (five), disintegrative disorder (two), attention deficit hyperactivity disorder (ADHD) (one), schizophrenia (one), and dyslexia (one). The tissue specimens were reviewed by three pathologists and compared with 22 well children and 2o with ulcerative colitis. Their data for GI pathology in the affected cohort were striking:

"Ileal LNH was present in 54 of 58 (93%) affected children and in five of 35 (14.3%) controls . Colonic LNH was present in 18 of 60 (30%) affected children and in two of 37 (5.4%) controls. Histologically, reactive follicular hyperplasia was present in 46 of 52 (88.5%) ileal biopsies from affected children and in four of 14 (29%) with UC, but not in non-IBD controls. Chronic colitis was identified in 53 of 60 (88%) affected children compared with one of 22 (4.5%) controls and in 20 of 20 (100%) with UC. Scores of frequency and severity of inflammation were significantly greater in both affected children and those with UC, compared with controls."

Considering the impact of the enteric (gut) immune and nervous systems on the brain these findings are not a surprise. "When the gut is inflamed the brain is inflamed." The authors conclude by stating:

"A new variant of inflammatory bowel disease is present in this group of children with developmental disorders."

A paper published last year in the Canadian Journal of Gastroenterology adds to the discussion of this topic in regard to autism. The authors state:

"There have been several reports of a link between autism and chronic gastrointestinal symptoms. Endoscopy trials have demonstrated a higher prevalence of nonspecific colitis, lymphoid hyperplasia and focally enhanced gastritis compared with controls. Postulated mechanisms include aberrant immune responses to some dietary proteins, abnormal intestinal permeability and unfavourable gut microflora."

The authors examined two autism spectrum disorder patients with chronic intestinal symptoms and abnormal endoscopies and reviewed relevant background studies. Their findings inspired this conclusion:

"While genetic susceptibility is an important contributor in ASDs, the exact etiology of these pervasive developmental disorders remains unclear and is most likely multi-factorial...Be it an immune-mediated connection, versus a 'brain-gut axis' interplay such as seen in irritable bowel syndrome, the increased prevalence of GI symptoms in this group of patients cannot be denied, nor the added distress that these symptoms could have on an individual who is already communicatively challenged...a heightened awareness and lower threshold for work-up and management of GI symptoms may help improve quality of life of these patients who may be suffering in silence."

The authors of a paper published in the Journal of Neuroimmunology consider lymphocyte subsets and inflammatory cytokines in the gut in relation to autism:

"Gastrointestinal pathology, characterized by lymphoid nodular hyperplasia and entero-colitis, has been demonstrated in a cohort of children with autistic spectrum disorder (ASD)."

They assessed inflammation in the intestines of ASD children in comparison with well controls and children with Crohn's disease by examining inflammatory cytokines present in CD3+ lymphocytes (T helper and cytotoxic T cells):

"In both peripheral blood and mucosa, CD3+ TNFα+ and CD3+ IFNγ+ [pro-inflammatory cytokines] were increased in ASD children compared with NIC [non-inflamed controls] and reached levels similar to CD [Crohn's disease]. In contrast, peripheral and mucosal CD3+ IL-10+ [anti-inflammatory cytokine] were markedly lower in ASD children with GI symptoms compared with both NIC and CD controls. In addition, mucosal CD3+ IL-4+ [pro-inflammatory] cells were increased in ASD compared with NIC."

Again we see a marked pattern of gastrointestinal inflammation distinguishing the ASD group. The authors conclude:

"There is a unique pattern of peripheral blood and mucosal CD3+ lymphocytes intracellular cytokines, which is consistent with significant immune dysregulation, in this ASD cohort."

Disorders of learning, behavior and neurodevelopment in childhood and adolescence are a heterogenous group with multiple possible causes so it would be an error to expect that all children with ASD have GI pathology and a principal or accessory cause. But it would be an equal error to fail to confirm whether or not it is a contributing factor in each individual case.