BACKGROUND: Intestinal mucosal pathology, characterized by ileo-colonic lymphoid 
nodular hyperplasia (LNH) and mild acute and chronic inflammation of the 
colorectum, small bowel and stomach, has been reported in children with autistic 
spectrum disorder (ASD).
AIM: To assess ileo-colonic LNH in ASD and control children and to test the 
hypothesis that there is an association between ileo-colonic LNH and ASD in 
children.
PATIENTS AND METHODS: One hundred and forty-eight consecutive children with ASD 
(median age 6 years; range 2-16; 127 male) with gastrointestinal symptoms were 
investigated by ileo-colonoscopy. Macroscopic and histological features were 
scored and compared with 30 developmentally normal (non-inflammatory bowel 
disease, non-coeliac disease) controls (median age 7 years; range 1-11; 25 male) 
showing mild non-specific colitis in 16 cases (13 male) and normal colonic 
histology in 14 cases (12 male). Seventy-four ASD children and 23 controls also 
underwent upper gastrointestinal endoscopy. The influence on ileal LNH of 
dietary restriction, age at colonoscopy, and co-existent LNH elsewhere in the 
intestine, was examined.
RESULTS: The prevalence of LNH was significantly greater in ASD children 
compared with controls in the ileum (129/144 (90%) vs. 8/27 (30%), P < 0.0001) 
and colon (88/148 (59%) vs. 7/30 (23%), P = 0.0003), whether or not controls had 
co-existent colonic inflammation. The severity of ileal LNH was significantly 
greater in ASD children compared with controls, with moderate to severe ileal 
LNH present in 98 of 144 (68%) ASD children versus 4 of 27 (15%) controls (P < 
0.0001). Severe ileal LNH was associated with co-existent colonic LNH in ASD 
children (P = 0.01). The presence and severity of ileal LNH was not influenced 
by either diet or age at colonoscopy (P = 0.2). Isolated ileal LNH without 
evidence of pathology elsewhere in the intestine was a rare event, occurring in 
less than 3% of children overall. On histopathological examination, hyperplastic 
lymphoid follicles are significantly more prevalent in the ileum of ASD children 
(84/138; 61%) compared with controls (2/23; 9%, P = 0.0001).
CONCLUSION: Ileo-colonic LNH is a characteristic pathological finding in 
children with ASD and gastrointestinal symptoms, and is associated with mucosal 
inflammation. Differences in age at colonoscopy and diet do not account for 
these changes. The data support the hypothesis that LNH is a significant 
pathological finding in ASD children.