The association between obesity and FAP according to the updated ROME IV criteria had not been investigated before. In the current study, our analysis of that association revealed a higher prevalence of overweight/obesity among adolescents with FAP disorders compared to an age- and sex-matched control population. Our results are in line with studies that had demonstrated a correlation between body weight and FGID. Teitelbaum et al (8) showed a greater percentage of obese pediatric patients with constipation, gastroesophageal reflux disease, IBS, encopresis, and FAP compared with normal weight controls. In their study, functional disorders were assigned based on ROME II criteria without specification of subtypes of FAP. From another point of view, Bonilla et al (9) described a cohort from 2007-2008 with a prevalence of 20.2% obesity in patients with FGID, however, no comparison to healthy control group was performed. They showed that obesity was associated with poor outcome and disability at long term follow up. In our study the prevalence of overweight/obesity was higher, probably attributed to the combination of children with overweight and obesity as one group or to the increase in prevalence of obesity in the western world as part of the obesity epidemic. Other studies demonstrated higher percentages of recurrent abdominal pain (12) and FGID (7) in obese children. However, Malaty et al (12) used a non-validated questionnaire and the latter study was based on ROME III criteria for diagnosis of functional disorders.
Several factors may explain the association between obesity and FAP disorders. Dietary habits are a major factor in obesity development and previous studies showed the association between increased consumption of carbohydrates and high body weight (13, 14, 15). Carbohydrate malabsorption may cause gastrointestinal symptoms via the physiologic effects of both increased osmotic activity and increased gas production from bacterial fermentation (16). Moreover, there is some evidence that a low-FODMAP diet is effective in reducing IBS symptoms (17, 18). Recently, Schnabel et al showed an association between ultra-processed food (UPF) consumption and functional gastrointestinal disorders. In this large French cohort, an increase in UPF, which is characterized by high density of saturated fatty acids, sugar, sodium and low content of protective nutrients such as fibers, was associated with a higher risk of IBS. They also found that UPF consumption was associated with higher BMI. (19). In addition to dietary habits, sedentary lifestyle and lack of physical activity could be related to both obesity and functional pain (20).
A potential association between obesity, FGID and gastrointestinal motility disorders has also been described. Delayed gastric emptying and impaired antral motility were found in children with RAP, FAP, IBS or functional dyspepsia (21, 22). Several studies have shown delayed gastric emptying and gastric and gallbladder dysmotility in the obese individuals (23, 24). This may be attributed to increased gastric distention in the obese causing poor fundal and antral tone (25), altered sensitivity of mechanoreceptors in the stomach musculature (26) and abnormal perception of satiety signals (27). Another association between obesity and FGID is the gut microbiota. Increased risk of small intestinal bacterial overgrowth (28) and different gut microbiota composition (29) in obesity has been reported which might contribute to gastrointestinal dysmotility, excessive fermentation, altered visceral perception and gut permeability with their metabolites leading to pain-predominant FGID (30, 31). Finally, obesity and FGID share common psychological comorbidities, such as stress, depression, and anxiety, which can contribute to each other's development and aggravate each other (32,33,34).
The higher prevalence of overweight/obesity in females with FAP compared to controls may be attributed to several factors. Females are more prone to several gastrointestinal motility disorders, such as delayed gastric emptying, compared to males (35,36). It has been suggested that this difference may be caused by female ovarian hormones. Gender differences in intestinal microbiome in addition to microbiome difference in obese and normal weight children (37) may serve as an alternative explanation. Our study has demonstrated a few significant differences between children with FAP having overweight/obesity compared to normal weight children. We found that overweight/obese children had more hospitalizations attributed to their abdominal pain compared with normal weight children as described in other studies which suggested that pediatric obesity contributes significantly to increased health care utilization in children (38, 39). A possible explanation to increased health care utilization in children with obesity is comorbidities of obesity (38). In addition, children with obesity might be more symptomatic compared to children with normal weight (40). We also found that obese children with FAP are treated more frequently with PPI than non-obese children with FAP. Parkman et al (36) reported that obese patients with idiopathic gastroparesis tend to be more symptomatic compared to non-obese patients. Whether this is true to patients with FAP is to be elucidated. Although no relation between FAP subgroups and obesity was established in this study, children with FD were treated more frequently with PPI, in line with the ROME IV recommendations (3), compared to other FAP subgroups. Generally, overuse of PPI has been increasing in the last decade in hospitalized and ambulatory patients and their prescription continues to grow in all western countries (41).
The clinical implications of the findings of our current study relate to the management of overweight/obese children with FGID. Although this study could not indicate causality between obesity and FAP, the findings support a relation between these conditions. The treatment protocol of obese children with FAP should also focus on guidance for more thorough nutritional assessment targeted towards weight reduction together with other lifestyle changes (e.g., increase in physical activities) that may improve symptoms and prevent or at least minimize the need for medications and hospitalizations.
To the best of our knowledge, this is the first study to show an association between obesity and FAP diagnosed in children according to the updated ROME IV criteria for diagnosis of FAP which was made by a pediatric gastroenterologist in a clinic setting and not by collecting information from a self-administered questionnaire. This study is limited by its retrospective nature, missing more precise data on skinfold measurements, body composition, and other parameters. In addition, our control group might include children with FAP disorders, although we believe that due to the high number of children included, the percentage of children with FAP disorders would be similar to the general population. Lastly, a part of children with diagnosis of FAP in the medical records did not fulfil the ROME IV criteria and therefore were excluded. In real life, some degree of incompatibility between clinical diagnosis and formal criteria may be anticipated. Another explanation is the difference between ROME IV and ROME III criteria, that was one of the rationales to conduct the current study.