Fructans Exacerbate Symptoms in a Subset of Children With Irritable Bowel Syndrome.

BACKGROUND & AIMS: Dietary fructans exacerbate symptoms in some, but not all, adults with irritable bowel syndrome (IBS). We sought to determine whether fructans worsen symptoms in children with IBS and whether clinical and psychosocial factors, and/or gas production, can identify those who are fructan sensitive. METHODS: We performed a double-blind placebo-controlled (maltodextrin) cross-over trial of 23 children with IBS, based on pediatric Rome III criteria, from September 2014 through December 2016. At baseline, participants completed 1-week pain and stool diaries and a 3-day food record and psychosocial factors (depression, anxiety, and somatization) were measured. Subjects were randomly assigned to groups that were provided meals for 72 hours containing either fructans or maltodextrin (0.5 g/kg; maximum, 19 g). Following a washout period of 10 days or more, the subjects received the meal they were not given during the first study period (crossed over). Gastrointestinal symptoms and breath hydrogen and methane production were captured during each meal period. Fructan sensitivity was defined as an increase of 30% or more in abdominal pain frequency following fructan ingestion. RESULTS: Subjects had more mean episodes of abdominal pain/day during the fructan-containing diet (3.4 ± 2.6) vs the maltodextrin-containing diet (2.4 ± 1.7) (P < .01), along with more severe bloating (P < .05) and flatulence (P = .01). Hydrogen (but not methane) production was greater while subjects were on the fructan-containing diet (617 ± 305 ppm∗h) than the maltodextrin-containing diet (136 ± 78 ppm*h) (P < .001). Eighteen subjects (78.2%) had more frequent abdominal pain while on the fructan-containing diet and 12 (52.2%) qualified as fructan sensitive. We found no difference between fructan-sensitive and fructan-insensitive subjects in baseline abdominal pain or bowel movement characteristics, dietary intake, psychosocial parameters, IBS subtype, or gas production. CONCLUSIONS: In a randomized controlled trial of children with IBS, we found fructans to exacerbate several symptoms. However, fructan sensitivity cannot be identified based on baseline gastrointestinal symptoms, dietary intake, psychosocial factors, or gas production. Clinicaltrials.gov no: NCT02842281.

A randomized trial to study the comparative efficacy of phenylbutyrate and benzoate on nitrogen excretion and ureagenesis in healthy volunteers.

PURPOSE: Benzoate and phenylbutyrate are widely used in the treatment of urea cycle disorders, but detailed studies on pharmacokinetics and comparative efficacy on nitrogen excretion are lacking. METHODS: We conducted a randomized, three-arm, crossover trial in healthy volunteers to study pharmacokinetics and comparative efficacy of phenylbutyrate (NaPB; 7.15 g•m-2BSA•day-1), benzoate (NaBz; 5.5 g•m-2BSA•day-1), and a combination of two medications (MIX arm; 3.575 g NaPB and 2.75 g NaBz•m-2BSA•day-1) on nitrogen excretion. Stable isotopes were used to study effects on urea production and dietary nitrogen disposal. RESULTS: The conjugation efficacy for both phenylbutyrate and benzoate was 65%; conjugation was superior at the lower dose used in the MIX arm. Whereas NaPB and MIX treatments were more effective at excreting nitrogen than NaBz, nitrogen excretion as a drug conjugate was similar between phenylbutyrate and MIX arms. Nitrogen excreted per USD was higher with combination therapy compared with NaPB. CONCLUSION: Phenylbutyrate was more effective than benzoate at disposing nitrogen. Increasing phenylbutyrate dose may not result in higher nitrogen excretion due to decreased conjugation efficiency at higher doses. Combinatorial therapy with phenylbutyrate and benzoate has the potential to significantly decrease treatment cost without compromising the nitrogen disposal efficacy.

Evaluation of FODMAP Carbohydrates Content in Selected Foods in the United States.

We analyzed the fermentable oligosaccharide, disaccharide, monosaccharide, and polyols (FODMAP) content of several foods potentially low in FODMAP which are commonly consumed by children. We determined that several processed foods (eg, gluten-free baked products) had unlabeled FODMAP content. Determining FODMAP content within foods distributed in the US may support educational and dietary interventions.

Factors Associated With Adherence to a Low Fermentable Carbohydrate Diet in Children With Functional Gastrointestinal Disorders.

BACKGROUND: The low-fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet (LFD) has been associated with reduced symptomology in pediatric functional gastrointestinal disorders (FGIDs). The LFD is a complex dietary intervention that may be difficult to follow; thus, there is great interest in determining factors that contribute to adherence. OBJECTIVE: To examine whether baseline abdominal pain, emotional/behavioral problems, or quality of life predict adherence to the LFD in children with FGIDs. DESIGN: This was a single-group pre-post intervention design within a larger randomized controlled trial. PARTICIPANTS/SETTING: Thirty 7- to 12-year-old children with FGIDs were recruited from pediatric gastrointestinal and primary care settings throughout Texas from 2019 to 2021. Evaluated participants were randomized to an LFD intervention as part of a larger randomized controlled trial. INTERVENTION: Participants received dietary counseling and followed the LFD for 3 weeks. MEASURES: Emotional or behavioral problems and quality of life were obtained via parent report, and abdominal pain was measured via child report. Adherence was assessed by using diet records and computed by a decrease in consumption of overall FODMAP intake. STATISTICAL ANALYSES PERFORMED: A hierarchical generalized linear mixed regression model examined factors associated with adherence. RESULTS: Greater baseline quality of life was associated with better adherence to the LFD (beta coefficient ß = -.02, P = 0.03), and baseline emotional/behavioral problems and abdominal pain complaints were not significantly associated with adherence (all Ps > 0.28). CONCLUSIONS: Higher child quality of life as reported by parents was related to increased adherence to this complex dietary intervention.

Children with functional abdominal pain disorders successfully decrease FODMAP food intake on a low FODMAP diet with modest improvements in nutritional intake and diet quality.

BACKGROUND: We sought to determine how a low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet (LFD) affected high FODMAP food intake, nutrient intake, and diet quality in children with functional abdominal pain disorders (FAPD). METHODS: Children (ages 7-13 years) with Rome IV FAPD began a dietitian-guided LFD. Three-day food records were captured at baseline and 2-3 weeks into the LFD. Intake of high FODMAP foods, energy, macronutrients, micronutrients, food groups, and ultra-processed foods were determined. KEY RESULTS: Median age of participants was 11 years, and 19/31 (61%) were female. Twenty-eight (90%) decreased high FODMAP food intake on the LFD: overall median (25-75%) high FODMAP foods/day decreased from 5.7 (3.6-7.3) to 2 (0.3-3.7) (p < 0.001). A more adherent subset (n = 22/71%) of participants consumed on average ≤3 high FODMAP foods per day during the LFD. Baseline nutritional intake and quality were generally poor with several micronutrient deficiencies identified. Diet quality improved on the LFD with increased servings of vegetables and protein and decreased consumption of ultra-processed foods, trans-fatty acids, and added sugars. On the LFD, there were significant decreases in total carbohydrates and thiamin (remained within recommended intake) and significant increases in vitamin B6 (p = 0.029), vitamin C (p = 0.019), and vitamin E (p = 0.009). Children more adherent to the LFD further increased vitamin D, magnesium, potassium, and fat servings. CONCLUSIONS AND INFERENCES: The majority of children with FAPD on a dietitian-led LFD successfully decreased high FODMAP food intake. Children with FAPD on the LFD (vs. baseline) modestly improved micronutrient intake and diet quality.

Fructan-sensitive children with irritable bowel syndrome have distinct gut microbiome signatures.

BACKGROUND: Dietary fructans may worsen gastrointestinal symptoms in children with irritable bowel syndrome (IBS). AIM: To determine whether gut microbiome composition and function are associated with childhood IBS fructan-induced symptoms. METHODS: Faecal samples were collected from 38 children aged 7-17 years with paediatric Rome III IBS, who previously completied a double-blind, randomised, placebo-controlled crossover (fructan vs maltodextrin) trial. Fructan sensitivity was defined as an increase of ≥30% in abdominal pain frequency during the fructan diet. Gut microbial composition was determined via 16Sv4 rDNA sequencing. LEfSe evaluated taxonomic composition differences. Tax4Fun2 predicted microbial fructan metabolic pathways. RESULTS: At baseline, 17 fructan-sensitive (vs 21 fructan-tolerant) subjects had lower alpha diversity (q < 0.05) and were enriched in the genus Holdermania. In contrast, fructan-tolerant subjects were enriched in 14 genera from the class Clostridia. During the fructan diet, fructan-sensitive (vs tolerant) subjects were enriched in both Agathobacter (P = 0.02) and Cyanobacteria (P = 0.0001). In contrast, fructan-tolerant subjects were enriched in three genera from the Clostridia class. Comparing the fructan vs maltodextrin diet, fructan-sensitive subjects had a significantly increased relative abundance of Bifidobacterium (P = 0.02) while fructan-tolerant subjects had increased Anaerostipes (P = 0.03) during the fructan diet. Only fructan-sensitive subjects had a trend towards increased predicted ß-fructofuranosidase during the fructan vs maltodextrin diet. CONCLUSIONS: Fructan-sensitive children with IBS have distinct gut microbiome signatures. These microbiome signatures differ both at baseline and in response to a fructan challenge.

Lipodystrophy syndrome in human immunodeficiency virus-infected children.

BACKGROUND: Lipodystrophy syndrome in HIV-infected adults is characterized by a variety of physical and/or metabolic abnormalities, including fat redistribution, hyperlipidemia (hypercholesterolemia and/or hypertriglyceridemia) and peripheral insulin resistance. Many studies suggest that antiretroviral therapy is the underlying cause of the condition. Few data exist for HIV-infected children. METHODS: This is a cross-sectional study evaluating HIV-infected children age 2 to 16 years. Fat redistribution was identified by physical examination and parental questionnaire. Fasting blood analysis included cholesterol, triglycerides, high density lipoprotein, low density lipoprotein, glucose, insulin and C-peptide. RESULTS: Forty HIV-infected children were recruited. Seven children (18%) exhibited physical signs of fat redistribution. Twenty-seven (68%), 11 (28%) and 3 (8%) children exhibited evidence for hypercholesterolemia, hypertriglyceridemia and insulin resistance, respectively. Eleven children (28%) had no physical signs or laboratory evidence of lipodystrophy. Statistical analysis did not reveal any significant association between the presence of lipodystrophic features and patient age, HIV-1 viral load, exposure to specific antiretroviral medications or duration of protease inhibitor or nucleoside reverse transcriptase inhibitor therapy. Drug dosing was significantly associated with the development of lipodystrophy features. Children receiving pediatric dosing regimens vs. adult dosing regimens were less likely to develop lipodystrophy (P = 0.003). CONCLUSIONS: Features associated with lipodystrophy syndrome arise in some HIV-infected children. Subjects receiving pediatric dosing regimens were less likely than those receiving adult regimens to develop lipodystrophy.

Gut microbiota influences low fermentable substrate diet efficacy in children with irritable bowel syndrome.

We sought to determine whether a low fermentable substrate diet (LFSD) decreases abdominal pain frequency in children with irritable bowel syndrome (IBS) and to identify potential microbial factors related to diet efficacy. Pain symptoms, stooling characteristics, breath hydrogen and methane, whole intestinal transit time, stool microbiome, and metabolite composition were collected and/or documented in eight children with IBS at baseline and during one week of an LFSD intervention. Pain frequency (P<0.05), pain severity (P<0.05), and pain-related interference with activities (P<0.05) decreased in the subjects while on the LFSD. Responders vs. non-responders: four children (50%) were identified as responders (> 50% decrease in abdominal pain frequency while on the LFSD). There were no differences between responders and non-responders with respect to hydrogen production, methane production, stooling characteristics, or gut transit time. Responders were characterized by increased pre-LFSD abundance of bacterial taxa belonging to the genera Sporobacter (P<0.05) and Subdoligranulum (P<0.02) and decreased abundance of taxa belonging to Bacteroides (P<0.05) relative to non-responders. In parallel, stool metabolites differed between responders and non-responders and were associated with differences in microbiome composition. These pilot study results suggest that an LFSD may be effective in decreasing GI symptoms in children with IBS. Microbial factors such as gut microbiome composition and stool metabolites while on the diet may relate to LFSD efficacy.