Sex-Dependent Efficacy of Dietary Fiber in Pediatric Functional Abdominal Pain

BACKGROUND AND AIMS:Functional abdominal pain disorders (FAPDs) are more prevalent in females. Dietary fiber may alleviate FAPDs symptoms; however, whether this effect is sex-dependent remains unclear. We investigated the sex-dependency of dietary fiber benefit on abdominal pain in children with FAPDs and explored the potential involvement of the gut microbiome. METHODS:In two cross-sectional cohorts of children with FAPDs (n=209) and healthy controls (HC; n=105), we correlated dietary fiber intake with abdominal pain symptoms after stratifying by sex. We also performed sex-stratified and sex-interaction analysis on data from a double-blind trial in children with irritable bowel syndrome (IBS) randomized to psyllium fiber (n=39) or placebo (n=49) for six weeks. Shotgun metagenomics was used to investigate gut microbiome community changes potentially linking dietary fiber intake with abdominal pain. RESULTS:In the cross-sectional cohorts, fiber intake inversely correlated with pain symptoms in boys (pain episodes: r= -0.24, P=0.005; pain days: r= -0.24, P=0.004) but not in girls. Similarly, in the randomized trial, psyllium fiber reduced the number of pain episodes in boys (P=.012), but not in girls. Generalized linear regression models confirmed that boys treated with psyllium fiber had greater reduction in pain episodes than girls (P=.007 for fiber x sex x time interaction). Age, sexual development, IBS subtype, stool form and microbiome composition were not significant determinants in the dietary fiber effects on pain reduction. CONCLUSIONS:Dietary fiber preferentially reduces abdominal pain frequency in boys, highlighting the importance of considering sex in future dietary intervention studies for FAPDs. ClincialTrials.gov number, NCT00526903.