DOES SMALL INTESTINE-LIVER AXIS PLAY A ROLE IN PEDIATRIC OBESITY RELATED LIVER DAMAGE ? A PILOT STUDY

Abstract

Background: Studies in an obese animal model and in some obese adults have recently suggested that a derangement of the small intestine-liver axis may play a role in the development of obesity related liver abnormalities. Aim & Methods: To examine small intestinal data [basal & lactulose H2 breath test (BT), permeability to mannitol/cellobiose (spectrophotometric method), serum levels of circulating bound endotoxins (LAL chromogenous method) and of Abs to bacterial wall products (peptidoglycan-polysaccharide (PG-PS) polymers; ELISA test) which reach the liver through the portal flow] in obese children (age 6-13 y) with and without hypertransaminasemia and/or ultrasonographic (US) bright liver not due to other causes of hepatopathy. Results: Up to now we have enrolled 27 obese children with [group 1, n = 16, mean age 10.8 y; BMI 30.6; ALT 52 ± 25 U/L) and without (group 2, n = 11, mean age 10.5 y (p = NS); BMI 27.5 (p = NS), ALT 21 ± 9 U/L (P = 0.001)] liver disease. 100% pts had familial obesity; 75% vs. 36% had familial history of liver disease (p = 0.06). Obesity duration, food habits, skinfold tickness and body circumferences, bioimpedance analysis of % lean and fat mass, visceral and subcutaneous US fat, serum lipids, IL6, TNFa and iron status were comparable in the two groups. As expected, fasting insulin to glucose ratios (FGIR) and n. insulin-resistant (FGIR <7) pts were different between groups [(5.5 ± 2.9 vs. 8.2 ± 4.1 (p = 0.05) and 12/16 vs. 4/11 (p = 0.06), respectively]. As for intestinal data, there were no differences in prevalence of small intestine bacterial overgrowth evaluated by H2 BT and abnormalities of intestinal permeability (1 case/group) & serum levels of bound endotoxins (9.2 ± 4.0 vs 12.0 ± 6.5 pg/ml). Serum IgA (but not IgG and IgM) Abs to PG-PS were significantly higher in group 1 (1.0 ± 0.4 vs. 0.7 ± 0.2 pg/ml; p < 0.05). We are now evaluating changes of the aforementioned data during a double blind treament with probiotics vs. placebo. Summary & Conclusions: Apart from Abs to PG-PS, so far we have not found relevant evidences suggesting that intestinal abnormalities may greatly contribute towards liver damage in pediatric obese children.(Acknowledgements: Italian MIUR 2003 & ELFID).