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Serum, Urine, and Fecal Metabolome Alterations in the Gut Microbiota in Response to Lifestyle Interventions in Pediatric Obesity: A Non-Randomized Clinical Trial.
Lee, Y, Cho, JY, Cho, KY
Nutrients. 2023;15(9)
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Paediatric obesity is linked to an increased risk of type 2 diabetes, hypertension, dyslipidaemia, and metabolic syndrome. Diverse evidence suggests that obesity is associated with alterations in the gut microbiota and its metabolites. The aim of this study was to understand the metabolic pathways underlying paediatric obesity and the effect of intervention, which could provide guidance for the treatment of obesity. This study was a non-randomised clinical trial which enrolled 50 children with obesity and 22 normal-weight children aged 7–18 years. Results showed that imbalances in microbiota and metabolites were associated with both obesity and response to the intervention. The most distinct metabolic alterations in the obese group were branched-chain amino acid and purine changes. Authors conclude that the findings of their study could be valuable for identifying novel targets and biomarkers for the treatment of obesity.
Abstract
Pediatric obesity is associated with alterations in the gut microbiota and its metabolites. However, how they influence obesity and the effect of lifestyle interventions remains unknown.. In this non-randomized clinical trial, we analyzed metabolomes and microbial features to understand the associated metabolic pathways and the effect of lifestyle interventions on pediatric obesity. Anthropometric/biochemical data and fasting serum, urine, and fecal samples were collected at baseline and after an eight-week, weight-reduction lifestyle modification program. Post-intervention, children with obesity were classified into responder and non-responder groups based on changes in total body fat. At baseline, serum L-isoleucine and uric acid levels were significantly higher in children with obesity compared with those in normal-weight children and were positively correlated with obesogenic genera. Taurodeoxycholic and tauromuricholic α + β acid levels decreased significantly with obesity and were negatively correlated with obesogenic genera. Branched-chain amino acid and purine metabolisms were distinguished metabolic pathways in the obese group. Post-intervention, urinary myristic acid levels decreased significantly in the responder group, showing a significant positive correlation with Bacteroides. Fatty acid biosynthesis decreased significantly in the responder group. Thus, lifestyle intervention with weight loss is associated with changes in fatty acid biosynthesis, and myristic acid is a possible therapeutic target for pediatric obesity.
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Moderate Consumption of Beer (with and without Ethanol) and Menopausal Symptoms: Results from a Parallel Clinical Trial in Postmenopausal Women.
Trius-Soler, M, Marhuenda-Muñoz, M, Laveriano-Santos, EP, Martínez-Huélamo, M, Sasot, G, Storniolo, CE, Estruch, R, Lamuela-Raventós, RM, Tresserra-Rimbau, A
Nutrients. 2021;13(7)
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During the menopause, hormonal changes can trigger uncomfortable symptoms such as hot flashes, night sweats, sleep disturbances, and vaginal dryness. Hormone replacement therapy does reduce some of the symptoms, however there has been an increased interest in alternative therapies such as phytoestrogens to relieve these symptoms. Phytoestrogens are compounds with oestrogen-like properties naturally found in plants. Beer is the main food source of the strongest phytoestrogen identified to date. The aim of this six-month parallel, controlled clinical intervention trial was to evaluate if a moderate daily intake of beer, with or without alcohol, could reduce menopausal symptoms in women. Female sex hormone profile and cardiovascular risk factors (CVRF) were also monitored. 34 postmenopausal women took part. One group included alcoholic beer (AB), and a second group added non-alcoholic beer (NAB) for 6 months. The control group took no alcohol in this time. After a 6-month follow-up both groups (AB and NAB) significantly reduced the severity of the menopause-related symptoms. These results must be considered as preliminary and will require confirmation with larger sample sizes.
Abstract
The menopausal transition can be a challenging period for women's health and a trigger of uncomfortable symptoms. Beer is the main food source of isoxanthohumol, a precursor of 8-prenylnaringenin, the strongest phytoestrogen identified to date. As phytoestrogens are reported to reduce perimenopausal symptoms, we evaluated if a daily moderate consumption of beer with (AB) and without alcohol (NAB) could improve menopausal symptoms and modify cardiovascular risk factors. A total of 37 postmenopausal women were enrolled in a parallel controlled intervention trial and assigned to three study groups: 16 were administered AB (330 mL/day), 7 NAB (660 mL/day), and 14 were in the control group. After a 6-month follow-up of the 34 participants who finished the trial, both interventions (AB and NAB) significantly reduced the severity of the menopause-related symptoms (p-value AB vs. Control: 0.009; p-value NAB vs. Control: 0.033). Moreover, AB had a beneficial net effect on psychological menopausal discomforts compared to the control group. As the sex hormone profile did not differ significantly between the study groups, the effects of both types of beers (AB and NAB) are attributed to the non-alcoholic fraction of beer. Furthermore, moderate NAB consumption improved the lipid profile and decreased blood pressure in postmenopausal women.
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A Pecan-Rich Diet Improves Cardiometabolic Risk Factors in Overweight and Obese Adults: A Randomized Controlled Trial.
McKay, DL, Eliasziw, M, Chen, CYO, Blumberg, JB
Nutrients. 2018;10(3)
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There has been a global rise in cardiovascular disease (CVD) and type 2 diabetes mellitus (TD2M) and dietary risk factors are a known contributor. While evidence has shown that an increased intake of tree nuts is associated with a reduced risk of disease indicators, there is limited research specifically on the effects of pecans. The aim of this randomised crossover trial was to assess the impact of pecan consumption on biomarkers related to CVD and T2DM risk in 26 overweight or obese women. Participants consumed a pecan-rich diet with an iso-caloric control diet of similar fat and fibre content, but absent in nuts, for four weeks with a two-week washout period. This trial demonstrated that displacing a portion of saturated fat in the typical American diet with pecans has a protective effect for CVD and TD2M. Based on these results, the authors recommend using dietary change as a first-line approach to disease prevention and management and suggest further studies be done to better understand potential benefits and associated mechanisms.
Abstract
Evidence from observational and intervention studies has shown a high intake of tree nuts is associated with a reduced risk of cardiovascular disease (CVD), mortality from type 2 diabetes (T2DM), and all-cause mortality. However, there is limited data regarding their effects on indicators of cardiometabolic risk other than hypercholesterolemia, and little is known about the demonstrable health benefits of pecans (Carya illinoensis (Wangenh.) K.Koch). We conducted a randomized, controlled feeding trial to compare the effects of a pecan-rich diet with an isocaloric control diet similar in total fat and fiber content, but absent nuts, on biomarkers related to CVD and T2DM risk in healthy middle-aged and older adults who are overweight or obese with central adiposity. After 4 weeks on a pecan-rich diet, changes in serum insulin, insulin resistance (HOMA-IR) and beta cell function (HOMA-β) were significantly greater than after the control diet (p < 0.05). Pecan consumption also lowered the risk of cardiometabolic disease as indicated by a composite score reflecting changes in clinically relevant markers. Thus, compared to the control diet, the pecan intervention had a concurrent and clinically significant effect on several relevant markers of cardiometabolic risk.
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The effect of pegylated human recombinant leptin (PEG-OB) on neuroendocrine adaptations to semi-starvation in overweight men.
Hukshorn, CJ, Menheere, PP, Westerterp-Plantenga, MS, Saris, WH
European journal of endocrinology. 2003;148(6):649-55
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Starvation results in a response in neuroendocrine system including suppression of some systems (such as thyroid and reproduction) and stimulation of others (such as the stress response). The mechanisms that cause these system responses remain unclear. Research has suggested that the hormone leptin (secreted by adipose tissue) may have a role in the physiological response to fasting. During periods of fasting, leptin levels can drop steeply and leptin given to starved rodents has shown an impact on the neuroendocrine system (such as the thyroid, adrenal and reproductive). This study explored whether raised leptin levels (administered in the form of long-acting pegylated recombinant leptin (PEG-OB)) had an impact on the neuroendocrine system responses to semi-starvation. In this randomised, double blind, placebo controlled trial, 24 overweight men (BMI 25-32) were prescribed a very low energy diet (500 kilocalorie) over 46 days to induce semi-starvation. Subjects either received 80mg of PEG-OB or a placebo. Hormones were measured (including those key to the thyroid, adrenal, somatotropic and sympathetic nervous system) using blood and urine samples. The results showed that men in the PEG-OB achieved significantly more weight loss (2.8kg). However, this did not reverse the fasting induced changes in key hormonal systems. The exception was luteinising hormone (LH) which was lower in the PEG-OB group compared to the placebo. The authors concluded that a lower level of leptin resulting from starvation may be a component of fasting induced changes in the reproductive system.
Abstract
OBJECTIVE Starvation induces a complex neuroendocrine response in humans thought to have evolved to defend against reduced energy intake. The drop in leptin levels observed during fasting has been implicated as a factor that triggers this adaptive response. To explore this hypothesis, we executed a randomized, double-blind, placebo-controlled study to investigate whether elevated leptin levels using long-acting pegylated human recombinant leptin (PEG-OB) influenced the neuroendocrine responses to semi-starvation in human subjects. DESIGN Twenty-four overweight male subjects (mean+/-s.e.m.; 34.8+/-1.3 yrs; 28.8+/-0.5 kg/m(2)) were prescribed a very low energy diet (2.1 MJ/day) to induce a state of semi-starvation for the next 46 days. In addition, all subjects received a weekly treatment of 80 mg PEG-OB or matching placebo. Hormone measurements were performed throughout the study period and included 5-h frequent hormone samplings and 24-h urine collections. RESULTS Weekly subcutaneous administration of PEG-OB led to significant additional weight loss (2.8 kg) but it did not reverse the fasting-induced changes in the thyroid, corticotropic, somatotropic axes and sympathetic nervous system activity. However, after adjustment for weight loss, the drop in mean luteinizing hormone levels was attenuated in the PEG-OB group compared with the placebo group. CONCLUSIONS These results suggest that a reduced level of leptin accompanying food restriction might be a component of the fasting-induced neuroendocrine inhibition of the human reproductive axis.
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Metabolism of phytanic acid and 3-methyl-adipic acid excretion in patients with adult Refsum disease.
Wierzbicki, AS, Mayne, PD, Lloyd, MD, Burston, D, Mei, G, Sidey, MC, Feher, MD, Gibberd, FB
Journal of lipid research. 2003;44(8):1481-8
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Phytanic acid (PA) is a branched-chain fatty acid, found in many animal products, that, unlike most fatty acids, cannot be metabolised by beta-oxidation. Instead, it undergoes alpha-oxidation in the peroxisome. Adult Refsum Disease is a genetic neurological disease, in which alpha-oxidation is impaired, resulting in the accumulation of PA in nerves and fat tissues. Other pathways for the metabolism of PA are not fully understood, such as omega-oxidation, which results in the production of 3-methyl-organic acids (3-MAA). This study assessed the contribution of the omega-oxidation pathway to the metabolism of PA by measuring 3-MAA excretion in patients with ARD. Eleven patients with ARD were put on a low-PA diet for 12 weeks. Blood, urine and tissue samples were taken at the start and end of the 12-week period to assess levels of PA and its metabolites. The low-PA diet led to an average 21% fall in blood PA levels over 12 weeks. The capacity of the omega-oxidation pathway was 6.9mg PA/day. The authors concluded that the omega-oxidation pathway can metabolise PA ingested by patients with ARD. Therefore, omega-oxidation is a potential target for therapeutic intervention to reduce PA levels in ARD patients.
Abstract
Adult Refsum disease (ARD) is associated with defective alpha-oxidation of phytanic acid (PA). omega-Oxidation of PA to 3-methyl-adipic acid (3-MAA) occurs although its clinical significance is unclear. In a 40 day study of a new ARD patient, where the plasma half-life of PA was 22.4 days, omega-oxidation accounted for 30% initially and later all PA excretion. Plasma and adipose tissue PA and 3-MAA excretion were measured in a cross-sectional study of 11 patients. The capacity of the omega-oxidation pathway was 6.9 (2.8-19.4) mg [20.4 (8.3-57.4) micromol] PA/day. 3-MAA excretion correlated with plasma PA levels (r = 0.61; P = 0.03) but not adipose tissue PA content. omega-Oxidation during a 56 h fast was studied in five patients. 3-MAA excretion increased by 208 +/- 58% in parallel with the 158 (125-603)% rise in plasma PA. Plasma PA doubled every 29 h, while 3-MAA excretion followed second-order kinetics. Acute sequelae of ARD were noted in three patients (60%) after fasting. The omega-oxidation pathway can metabolise PA ingested by patients with ARD, but this activity is dependent on plasma PA concentration. omega-Oxidation forms a functional reserve capacity that enables patients with ARD undergoing acute stress to cope with limited increases in plasma PA levels.
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Insulin-like growth factor I response during nutritional rehabilitation of persistent diarrhoea.
Bhutta, ZA, Bang, P, Karlsson, E, Hagenäs, L, Nizami, SQ, Söder, O
Archives of disease in childhood. 1999;80(5):438-42
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Persistent diarrhoea in childhood causes severe malnutrition, and morbidity in 15%+ cases. Treatment includes nutritional rehabilitation for weight gain and diarrheal recovery. This study evaluates nutritional recovery (defined as weight gain (> 5 g/kg/day) with a resolution of diarrhea by day 7 of treatment), intestinal permeability and insulin-like growth factor I (IGF-I) response in malnourished children with faltering growth (aged 6-36 months) with persistent diarrhoea ((>/= 14 days) and their relation to concomitant systemic infection(s) (as indicated by serum C reactive protein (CRP)). For a minimum of 7 days, 63 children were fed a previously validated dietary regimen (data not available) of rice–lentil (khitchri) and yogurt aimed at providing at least 100 kcal/kg/day by day 3, with ad libitum feeds thereafter. Children were nursed on a research ward throughout. 49 children were treatment successes. They had a significant increase in serum IGF-I and IGF-I% correlated with weight gain. 14 children did not meet the criteria for nutritional recovery. They had higher serum CRP concentrations and sepsis at admission. They had lower mean (SD) weight gain in spite of overall mean energy intake being comparable with treatment successes. This may indicate malabsoption. Admission CRP concentration and IGF-I were negatively correlated. CRP concentrations at admission and corresponding individual IGF-I values over the 7 days treatment were significantly correlated. Significantly raised CRP concentrations in children with a correspondingly low IGF-I response may indicate a continued inflammatory or infected state in these children. Small but opposing trends of urinary excretion of the oral lactulose dose were seen in both groups over the seven days of treatment, indicating worsening enteropathy (mucosal injury) among treatment failures. None of the permeability parameters correlated with IGF-I at baseline or recovery. The study confirms that a traditional rice–lentil (khitchri) and yogurt diet can be used successfully for enteral nutritional rehabilitation in malnourished children with persistent diarrhoea and leads to adequate weight gain; Serum IGF-I levels correlates closely with weight gain and reduction in stool output; recovery is delayed with sepsis and raised blood CRP concentrations at admission; IGF-I is depressed at admission in children with persistent diarrhoea. The data provide evidence that serum IGF-I response in recovering malnourished children with persistent diarrhoea may provide a sensitive measure of nutritional and diarrhoeal recovery. Further studies are needed to evaluate factors regulating the IGF-I response in such children, especially the effect of intercurrent infections. Arbitrary definition of treatment failure is a study limitation.
Abstract
OBJECTIVE Evaluation of nutritional recovery, intestinal permeability, and insulin-like growth factor I (IGF-I) response in malnourished children with persistent diarrhoea and their relation to concomitant systemic infection(s). STUDY DESIGN Open study of severely malnourished children (aged 6-36 months) with persistent diarrhoea (≥ 14 days) admitted for nutritional rehabilitation with a standardised rice-lentil and yogurt diet. Successful recovery was defined prospectively as overall weight gain (> 5 g/kg/day) with a reduction in stool output by day 7 of treatment. Data on coexisting infections and serum C reactive protein (CRP) were collected at admission. RESULTS Of 63 children, 48 (group A) recovered within seven days of dietary treatment. These children had a significant increase in serum IGF-I (DeltaIGF-I%) and, in contrast to serum prealbumin and retinol binding protein, DeltaIGF-I% correlated with weight gain (r = 0.41). There was no correlation between the IGF-I response and intestinal permeability as assessed by urinary lactulose/rhamnose excretion. Treatment failures (group B) included more children with clinical (relative risk, 4.8; 95% confidence interval, 1.2 to 19.7) and culture proven sepsis at admission and higher concentrations of serum CRP (median (range), 36 (0-182) v 10 (0-240) mg/l) at admission. There was a negative correlation between admission CRP concentration and DeltaIGF-I% (r = -0.45). CONCLUSIONS In comparison with serum albumin, prealbumin, and retinol binding protein, serum IGF-I increment is a better marker of nutritional recovery in malnourished children with persistent diarrhoea. The possible association of systemic infections, serum IGF-I response, and mucosal recovery needs evaluation in future studies.
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A randomized controlled study comparing elemental diet and steroid treatment in Crohn's disease.
Zoli, G, Carè, M, Parazza, M, Spanò, C, Biagi, PL, Bernardi, M, Gasbarrini, G
Alimentary pharmacology & therapeutics. 1997;11(4):735-40
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An elemental diet is considered an effective primary treatment for active Crohn's disease, usually given by a feeding tube. This RCT evaluated the affect of elemental diet administered orally on disease activity, intestinal permeability and nutritional status when compared to high-dose corticosteroids. 22 Crohn’s disease patients were enrolled of which 2 withdrew and 20 were randomised to oral elemental diet group (n-10) or corticosteroid plus normal diet group (n=10) for 2 weeks. After 2 weeks clinical disease activity improved significantly in both groups. Crohn’s disease activity and erythrocyte sedimentation rate improved in the diet group. Crohn's disease activity improved in the corticosteroid group. Disease remission rate was higher in the diet group (n=8) compared to the corticosteroid group (n=5). 12 months after the study there was no difference in disease relapse rate between groups. Intestinal permeability was significantly improved in the diet group only. However, at the start of the study, permeability levels were randomly lower in the corticosteroid group than the diet group so it is not possible to say that elemental diet was more effective than corticosteroids in promoting gut mucosal healing. Nutritional status improved in both groups but was more evident in the diet group. The authors conclude that an oral elemental diet is effective in promoting and maintaining remission of Crohn’s disease activity, in restoring intestinal permeability and improving nutritional status, and is generally well tolerated with a high degree of compliance.
Abstract
BACKGROUND Elemental diet is considered an effective primary treatment for active Crohn's disease, but it is usually given by a feeding tube. METHODS Twenty-two patients (12 males, median age 30 years, range 18-60) with moderately active Crohn's disease were enrolled in a randomized study in which the efficacy of an elemental diet administered orally was compared to high-dose corticosteroids in achieving clinical and laboratory remission. Ten patients were treated by oral elemental diet (Peptamen, Clintec, USA) and 10 received corticosteroids. Both treatment regimens lasted 2 weeks. The two groups did not differ with respect to age, sex, body weight, location of disease, treatment or disease activity prior to the study. In all patients studied, simple Crohn's disease activity index, nutritional status (expressed as body mass index), percentage of ideal body weight, fat mass, fat free mass, erythrocyte sedimentation rate, interleukin-6, intestinal permeability (expressed as permeability index), prealbumin, retinol binding protein and multiskin test were evaluated before and after treatment. RESULTS After 2 weeks of treatment, there were significant improvements in simple Crohn's disease activity index, erythrocyte sedimentation rate, permeability index, body mass index, prealbumin, retinol binding protein and multiskin test in the elemental diet group. There were significant improvements in simple Crohn's disease activity index and fat free mass in the corticosteroid group. CONCLUSIONS These data suggest that, in the short term, an oral elemental diet is at least as effective as steroids in inducing remission of mild-moderately active Crohn's disease, but it may be more effective in improving the nutritional status of these patients, probably through a more rapid restoration of normal intestinal permeability.
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Randomised trial of safety and efficacy of immediate postoperative enteral feeding in patients undergoing gastrointestinal resection.
Carr, CS, Ling, KD, Boulos, P, Singer, M
BMJ (Clinical research ed.). 1996;312(7035):869-71
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Malnutrition predisposes patients to postoperative complications such as infection and a prolonged hospital stay. Postoperative gastric stasis causes nausea and vomiting thus inhibiting oral intake, but it has been shown that small bowel function continues. This randomised trial of 28 patients assessed the safely and efficacy of immediate post-operative enteral feeding in patients who had undergone gastrointestinal resection, compared to conventional intravenous fluids. The study found that the average caloric intake was significantly higher in enterally fed patients compared to those on intravenous fluids. Urinary nitrogen balance, a marker of nutritional status, was negative on the first postoperative day in those on intravenous fluids but positive in all 14 enterally fed patients. There was no change in gut mucosal permeability in the enterally fed group (assessed by lactulose:mannitol absorption ratio) but a significant increase from the test ratios seen before the operation in those on intravenous fluids. There were also fewer postoperative complications in the enterally fed group. Immediate postoperative enteral feeding in patients undergoing intestinal resection seems to be safe, prevents an increase in gut mucosal permeability, and produces a positive nitrogen balance. Postoperative enteral feeding may reduce the need for total parenteral nutrition and reduce expenditure and complications.
Abstract
OBJECTIVES To assess whether immediate post-operative enteral feeding in patients who have undergone gastrointestinal resection is safe and effective. DESIGN Randomised trial of immediate post-operative enteral feeding through a nasojejunal tube v conventional postoperative intravenous fluids until the reintroduction of normal diet. SETTING Teaching hospitals in London. SUBJECTS 30 patients under the care of the participating consultant surgeon who were undergoing elective laparotomies with a view to gastrointestinal resection for quiescent, chronic gastrointestinal disease. Two patients did not proceed to resection. MAIN OUTCOME MEASURES Nutritional state, nutritional intake and nitrogen balance, gut mucosal permeability measured by lactulose-mannitol differential sugar absorption test, complications, and outcome. RESULTS Successful immediate enteral feeding was established in all 14 patients with a mean (SD) daily intake of 6.78 (1.57)MJ (1622 (375) kcal before reintroduction of oral diet compared with 1.58 (0.14) MJ (377 (34) kcal) for those on intravenous fluids (P < 0.0001). Urinary nitrogen balance on the first postoperative day was negative in those on intravenous fluids but positive in all 14 enterally fed patients (mean (SD) - 13.2 (11.6) g v 5.3 (2.7) g; P < 0.005). There was no difference by day 5. There was no change in gut mucosal permeability in the enterally fed group but a significant increase from the test ratios seen before the operation in those on intravenous fluids (0.11(0.06) v 0.15 (0.12); P < 0.005). There were also fewer postoperative complications in the enterally fed group (P < 0.005). CONCLUSIONS Immediate postoperative enteral feeding in patients undergoing intestinal resection seems to be safe, prevents an increase in gut mucosal permeability, and produces a positive nitrogen balance.
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Dose dependent effects of protracted ingestion of small amounts of gliadin in coeliac disease children: a clinical and jejunal morphometric study.
Catassi, C, Rossini, M, Rätsch, IM, Bearzi, I, Santinelli, A, Castagnani, R, Pisani, E, Coppa, GV, Giorgi, PL
Gut. 1993;34(11):1515-9
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Coeliac disease (CD) is an intestinal reaction that is caused by the ingestion of gluten. While this is well established, the relationship between the quantity ingested and the severity of adverse effects, namely for small amounts of gluten, is still unclear. The aim of this study was to assess the effects of chronic ingestion of small amounts of gluten in children with CD. 20 children who had been on a long-term gluten-free diet were given a daily dose of either 100 mg or 500 mg of gliadin for four weeks. Effects were measured through an intestinal biopsy, antibody test and sugar intestinal permeability test. The findings of this study showed that in children with CD, chronic ingestion of gluten causes dose-dependent damage to intestinal mucosa and lymphocyte infiltration.
Abstract
This study aimed to investigate the effects of chronic ingestion of small amounts of gliadin on children with coeliac disease. A four week challenge was performed on 20 children who had been on a gluten free diet for mean (SD) 14 (3) months. They were given a daily dose of either 100 mg (group A, n = 10, mean age 4 (2) years) or 500 mg of gliadin (group B, mean age 5 (3) years). The effects of the gliadin were monitored by morphometric study of the jejunal mucosa, intestinal permeability test with cellobiose/mannitol, and serum antigliadin antibody test. After the challenge, group A patients showed a significant increase in the mean intraepithelial lymphocyte count (before challenge 11 (3), afterwards 19 (6)) and a decrease in the villous height/crypt depth ratio (beforehand 1.5 (0.1), afterwards 1.3 (0.2)), while the intestinal permeability test remained normal and the IgA-antigliadin antibody increased in four of 10 children. After the challenge group B showed more pronounced histological changes, an increase in the mean urinary cellobiose/mannitol % (beforehand 0.028 (0.020), afterwards 0.058 (0.028)), and IgA-antigliadin antibody positivity in six of eight subjects. The discriminant analysis function showed that the pretreatment group, group A after challenge, and group B after challenge were correctly classified in 90% of cases by functions based on the individual intraepithelial lymphocyte count and the villous height/crypt depth ratio. This study shows that chronic ingestion of small amounts of gluten causes dose-dependent damage to the small intestinal mucosa in children with coeliac disease. The predictive value of laboratory tests, such as the antigliadin antibody test and the intestinal permeability test seems to be lower in treated patients than in those with active coeliac disease.