Increased Intestinal Permeability and Decreased Resiliency of the Intestinal Barrier in Alcoholic Liver Disease.

INTRODUCTION: Only 20%-30% of individuals with alcohol use disorder (AUD) develop alcoholic liver disease (ALD). While the development of gut-derived endotoxemia is understood to be a required cofactor, increased intestinal permeability in ALD is not completely understood. METHODS: We recruited 178 subjects-58 healthy controls (HCs), 32 with ALD, 53 with AUD but no liver disease (ALC), and 35 with metabolic dysfunction-associated steatotic liver disease (MASLD). Intestinal permeability was assessed by a sugar cocktail as a percentage of oral dose. The permeability test was repeated after an aspirin challenge in a subset. RESULTS: Five-hour urinary lactulose/mannitol ratio (primarily representing small intestinal permeability) was not statistically different in HC, ALC, ALD, and MASLD groups ( P = 0.40). Twenty-four-hour urinary sucralose (representing whole gut permeability) was increased in ALD ( F = 5.3, P < 0.01) and distinguished ALD from ALC; 24-hour sucralose/lactulose ratio (primarily representing colon permeability) separated the ALD group ( F = 10.2, P < 0.01) from the MASLD group. After aspirin challenge, intestinal permeability increased in all groups and ALD had the largest increase. DISCUSSION: In a group of patients, we confirmed that (i) the ALD group has increased intestinal permeability compared with the HC, ALC, or MASLD group. In addition, because small bowel permeability (lactulose/mannitol ratio) is normal, the disruption of intestinal barrier seems to be primarily in the large intestine; (ii) decreased resiliency of intestinal barrier to injurious agents (such as NSAID) might be the mechanism for gut leak in subset of AUD who develop ALD.

Colonic Lactulose Fermentation Has No Impact on Glucagon-like Peptide-1 and Peptide-YY Secretion in Healthy Young Men.

CONTEXT: The colon houses most of humans' gut microbiota, which ferments indigestible carbohydrates. The products of fermentation have been proposed to influence the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) from the many endocrine cells in the colonic epithelium. However, little is known about the colonic contribution to fasting or postprandial plasma levels of L-cell products. OBJECTIVE: To determine the impact of colonic lactulose fermentation on gut peptide secretion and to evaluate whether colonic endocrine secretion contributes to gut hormone concentrations measurable in the fasting state. METHODS: Ten healthy young men were studied on 3 occasions after an overnight fast. On 2 study days, lactulose (20 g) was given orally and compared to water intake on a third study day. For 1 of the lactulose visits, participants underwent a full colonic evacuation. Over a 6-h study protocol, lactulose fermentation was assessed by measuring exhaled hydrogen, and gut peptide secretion, paracetamol, and short-chain fatty acid levels were measured in plasma. RESULTS: Colonic evacuation markedly reduced hydrogen exhalation after lactulose intake (P = 0.013). Our analysis suggests that the colon does not account for the measurable amounts of GLP-1 and PYY present in the circulation during fasting and that fermentation and peptide secretion are not acutely related. CONCLUSION: Whether colonic luminal contents affect colonic L-cell secretion sufficiently to influence circulating concentrations requires further investigation. Colonic evacuation markedly reduced lactulose fermentation, but hormone releases were unchanged in the present study.

Bifidobacterium response to lactulose ingestion in the gut relies on a solute-binding protein-dependent ABC transporter.

This study aims to understand the mechanistic basis underlying the response of Bifidobacterium to lactulose ingestion in guts of healthy Japanese subjects, with specific focus on a lactulose transporter. An in vitro assay using mutant strains of Bifidobacterium longum subsp. longum 105-A shows that a solute-binding protein with locus tag number BL105A_0502 (termed LT-SBP) is primarily involved in lactulose uptake. By quantifying faecal abundance of LT-SBP orthologues, which is defined by phylogenetic analysis, we find that subjects with 107 to 109 copies of the genes per gram of faeces before lactulose ingestion show a marked increase in Bifidobacterium after ingestion, suggesting the presence of thresholds between responders and non-responders to lactulose. These results help predict the prebiotics-responder and non-responder status and provide an insight into clinical interventions that test the efficacy of prebiotics.

Comparative effectiveness of lactulose and sennosides for the prevention of peritoneal dialysis-related peritonitis: an open-label, randomized, active-controlled trial.

BACKGROUND: To the best of our knowledge, the effectiveness and safety of lactulose in comparison to sennosides, for the prevention of peritoneal dialysis (PD)-related peritonitis, has never been tested in a randomized study. METHODS: We conducted an open-label, randomized, active-controlled trial in a PD-center in Northern Thailand. Adult patients on PD were enrolled and randomly assigned in a 1:1 ratio into two groups; one group received lactulose 15 mL once daily (n = 50) and the other group received sennosides two tablets daily (n = 50). The primary outcome was time-to-first bacterial peritonitis. The secondary outcomes included a composite of bacterial peritonitis and all-cause mortality. Cox proportional hazards regression was calculated and presented as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: One hundred PD patients were recruited (50.0% men; mean age 55.5 ± 13.0 years) in this study. The baseline characteristics of the study participants were similar in both groups. No significant trend towards a higher risk of PD-related peritonitis was observed in the lactulose group (HR, 2.32 [95% CI, 0.92-5.83]; p = .051) compared to the sennosides group. Nevertheless, the secondary outcome was significantly higher in the lactulose group (HR, 2.77 [95% CI, 1.20-6.41]; p = .010). The incidence of adverse events was not substantially different between the two groups; however, diarrhoea was more frequent in the lactulose group (38.0% vs. 18.0%; p = .030) than in the sennosides group. CONCLUSIONS: Treatment with lactulose is not more effective than sennosides and cannot be routinely recommended for the prevention of peritonitis among the PD population. TRIAL REGISTRATION Thai Clinical Trial Registry (clinicaltrials.in.th); ID: TCTR20171012001 KEY MESSAGE To the best of our knowledge, no randomized controlled trial that compares the efficacy and safety profiles of lactulose versus sennosides for the prevention of PD-related peritonitis among the PD population has been conducted. In this open-label, randomized, active-controlled trial, treatment with lactulose is not more effective than sennosides in the prevention of PD-related peritonitis, and it could increase the risk of bacterial PD-related peritonitis. Further studies with a larger sample size by incorporated real-world evidence are needed to confirm our findings and to explore strategies to prevent peritonitis among PD patients.

Simultaneous assessment of intestinal permeability and lactase activity in human-milk-fed preterm infants by sugar absorption test: Clinical implementation and analytical method.

BACKGROUND & AIMS: Experimental (nutritional) interventions in preterm infants frequently focus on intestinal maturation, as improving tolerance to enteral nutrition is a major goal. Intestinal permeability and lactase activity serve as markers for intestinal maturation. We aimed to develop a protocol for the simultaneous assessment of both markers in human-milk-fed preterm infants by a sugar absorption test. In addition, we developed a new gas chromatography-mass spectrometry (GC-MS) method for the analysis of lactulose, lactose, and mannitol in urine and milk collected during the sugar absorption test. METHODS: The sugar absorption test was performed on days 4, 7, and 14 postpartum in 12 preterm infants (gestational age of 26-32 weeks). Human milk was collected, pooled, and divided into equal portions to provide a stable lactose intake for 24 h. Urine was collected in the last 6 h of this 24 h period, after administration of a bolus test sugar solution. Samples were analyzed by GC-MS after derivatization by oxime formation combined with acetylation. RESULTS: The GC-MS method was validated and used for the accurate measurement of lactulose, lactose, and mannitol concentrations. The urinary lactulose/mannitol ratio declined with time, suggesting a decreased intestinal permeability. The urine-to-milk-lactulose/lactose ratio increased as a result of increased lactase activity with time. CONCLUSIONS: The developed protocol for simultaneous assessment of intestinal permeability and lactase activity can be used to monitor the effect of experimental (nutritional) interventions in human-milk-fed preterm infants. Urine and milk samples obtained during the sugar absorption test can be accurately analyzed by GC-MS.

Increased Intestinal Permeability Is Associated With Later Development of Crohn's Disease.

BACKGROUND & AIMS: Increased intestinal permeability has been associated with Crohn's disease (CD), but it is not clear whether it is a cause or result of the disease. We performed a prospective study to determine whether increased intestinal permeability is associated with future development of CD. METHODS: We assessed the intestinal permeability, measured by the urinary fractional excretion of lactulose-to-mannitol ratio (LMR) at recruitment in 1420 asymptomatic first-degree relatives (6-35 years old) of patients with CD (collected from 2008 through 2015). Participants were then followed up for a diagnosis of CD from 2008 to 2017, with a median follow-up time of 7.8 years. We analyzed data from 50 participants who developed CD after a median of 2.7 years during the study period, along with 1370 individuals who remained asymptomatic until October 2017. We used the Cox proportional hazards model to evaluate time-related risk of CD based on the baseline LMR. RESULTS: An abnormal LMR (>0.03) was associated with a diagnosis of CD during the follow-up period (hazard ratio, 3.03; 95% CI, 1.64-5.63; P = 3.97 × 10-4). This association remained significant even when the test was performed more than 3 years before the diagnosis of CD (hazard ratio, 1.62; 95% CI, 1.051-2.50; P = .029). CONCLUSIONS: Increased intestinal permeability is associated with later development of CD; these findings support a model in which altered intestinal barrier function contributes to pathogenesis. Abnormal gut barrier function might serve as a biomarker for risk of CD onset.

Comparative efficacy and safety of lactulose plus paraffin vs polyethylene glycol in functional constipation: a randomised clinical study.

BACKGROUND: Few head-to-head comparisons of the different classes of laxatives have been conducted. OBJECTIVE: The objective of this work is to compare the efficacy of lactulose plus paraffin vs polyethylene glycol in the treatment of functional constipation (non-inferiority study). METHODS: This randomised, parallel-group, multicentre phase 4 study recruited patients with functional constipation diagnosed according to Rome III criteria. Patients received lactulose plus paraffin or polyethylene glycol for 28 days. The primary end point was the change from baseline in the Patient Assessment of Constipation-Symptoms (PAC-SYM) score. RESULTS: A total of 363 patients were randomised to lactulose plus paraffin (n = 179) or polyethylene glycol (n = 184). On day 28, the mean PAC-SYM score decreased significantly vs baseline with both treatments (p < 0.001). The lower boundary of the 95% CI exceeded the pre-specified limit of -0.25, therefore establishing non-inferiority of lactulose plus paraffin vs polyethylene glycol. At least one adverse event occurred in 20 patients (11.2%) in the lactulose plus paraffin group and in 26 patients (14.2%) in the polyethylene glycol group, most of which were of mild or moderate severity and unrelated to study drugs. CONCLUSION: Lactulose plus paraffin may be used interchangeably with polyethylene glycol for the pharmacological treatment of functional constipation.Trial registration: EudraCT number 2015-003021-34.

Mechanisms of Action of Prebiotics and Their Effects on Gastro-Intestinal Disorders in Adults.

In recent years, research has focused on the use of dietary fibers and prebiotics, since many of these polysaccharides can be metabolized by intestinal microbiota, leading to the production of short-chain fatty acids. The metabolites of prebiotic fermentation also show anti-inflammatory and immunomodulatory capabilities, suggesting an interesting role in the treatment of several pathological conditions. Galacto-oligosaccharide and short- and long-chain fructans (Fructo-oligosaccharides and inulin) are the most studied prebiotics, even if other dietary compounds seem to show the same features. There is an increasing interest in dietary strategies to modulate microbiota. The aim of this review is to explore the mechanisms of action of prebiotics and their effects on the principal gastro-intestinal disorders in adults, with a special focus on Galacto-oligosaccharides, Fructo-oligosaccharides, lactulose and new emerging substances which currently have evidence of prebiotics effects, such as xilooligosaccharides, soybean oligosaccharides, isomaltooligosaccharides, lactobionic acid, resistant starch and polyphenols.

Effects of flaxseed supplementation on functional constipation and quality of life in a Chinese population: A randomized trial.

BACKGROUND AND OBJECTIVES: This prospective, randomized, controlled study aimed to evaluate the effects of flaxseed supplementation on functional constipation and quality of life in adult men and women in China. METHODS AND STUDY DESIGN: 90 subjects with functional constipation diagnosed by the Rome IV criteria were enrolled. Subjects were randomly assigned to receive either 50 g/day flaxseed flour with meals (n=60) or 15 mL/day of a lactulose solution on an empty stomach (n=30) every morning for 4 weeks. Wexner constipation scores, stool consistency according to the Bristol Stool Form Scale, and bowel habits (frequency of bowel movements/week, the time spent on defecation) were the primary outcomes. The change in Patient Assessment of Constipation Quality of Life score was the secondary outcome. RESULTS: After 4 weeks, the bowel habits in both groups were significantly improved. The median Wexner constipation score decreased from 14 to 6.5 in the flaxseed group (p<0.001) and from 15 to 9 in the lactulose group (p<0.001). The median defecation frequency per week increased significantly (2 to 7 for flaxseed and 2 to 6 for lactulose, p<0.001 for both groups). The Patient Assessment of Constipation Quality of Life score decreased significantly (-1.34 and -0.66 for flaxseed and lactulose, respectively; p<0.001 for both groups). CONCLUSIONS: Flaxseed flour is somewhat more effective at increasing defecation frequency than lactulose, improving bowel movements and promoting life quality of subjects with chronic functional constipation in the Chinese population.

Clinical management of type C hepatic encephalopathy.

Type-C hepatic encephalopathy is a complex neurological syndrome, characteristic of patients with liver disease, causing a wide and complex spectrum of nonspecific neurological and psychiatric manifestations, ranging from a subclinical entity, minimal hepatic encephalopathy, to a deep form in which a complete alteration of consciousness can be observed: overt hepatic encephalopathy. Overt hepatic encephalopathy occurs in 30-40% of patients. According to the time course, hepatic encephalopathy is subdivided into episodic, recurrent and persistent. Diagnostic strategies range from simple clinical scales to more complex psychometric and neurophysiological tools. Therapeutic options may vary between episodic hepatic encephalopathy, in which it is important to define and treat the precipitating factor and hepatic encephalopathy and secondary prophylaxis, where the standard of care is non-absorbable disaccharides and rifaximin. Grey areas and future needs remain the therapeutic approach to minimal hepatic encephalopathy and issues in the design of therapeutic studies for hepatic encephalopathy.

Subtype classification of functional constipation in children: polyethylene glycol versus lactulose.

BACKGROUND: This study aimed to evaluate the usefulness, from a therapeutic perspective, of classifying the subtypes of functional childhood constipation using a colon transit time (CTT) test. METHODS: A total of 190 children were enrolled in this study, which was based on data collected from a defecation diary, a CTT test, and medical records. RESULTS: Polyethylene glycol (PEG) 4000 was prescribed in 51.1% (N = 47/92) of normal transit type constipation cases (NT) and 91.8% (N = 90/98) of abnormal transit type constipation cases (P < 0.001). In terms of the subtype of CTT test, PEG 4000 was prescribed in 51.1% (N = 47/92) of NT cases, 96.2% (N = 25/26) of outlet obstruction type cases (OT), and 90.3% (N = 65/72) of slow transit type cases (ST) (P < 0.001). Polyethylene glycol 4000 was administered in 97.2% (N = 35/36) of the fecal incontinence group and 66.2% (N = 102/154) of the non-fecal incontinence group (P < 0.001). In the non-fecal incontinence group, PEG 4000 was prescribed in 47.3% (N = 40/84) of NT cases, 94.4% (N = 17/18) of OT cases, and 86.5% (N = 45/52) of ST cases (P < 0.001). In the fecal incontinence group, PEG 4000 was prescribed in 87.5% (N = 7/8) of NT cases, 100% (N = 8/8) of OT cases, and 100% (N = 20/20) of ST cases (P = 0.165). CONCLUSIONS: Subtype classification of functional constipation based on the CTT test provides important information for the initial choice of drugs in children.

The advantage of polyethylene glycol electrolyte solution combined with lactulose in patients with long interval preparation-to-colonoscopy.

BACKGROUND/AIMS: The main aim of the present study was to assess the efficacy of polyethylene glycol electrolyte (PEG) solution combined with lactulose in bowel preparation to find a new method for colonoscopy preparation to improve the quality of colonoscopy in patients with long interval preparation-to-colonoscopy (P-C). MATERIALS AND METHODS: A prospective, randomized, endoscopist-blinded and placebo-controlled study was conducted. Three hundred sixty patients who were scheduled for colonoscopy were enrolled in the study. They were randomly divided into the PEG-lactulose group and the PEG-placebo group with 180 patients per arm. Two of the most common methods for estimating the quality of bowel preparation were the use of the Boston Bowel Preparation Scale and the measurement of the Bubble Scale and adenoma detection rate (ADR) as a secondary outcome of observation. RESULTS: The PEG-lactulose group had a significant improvement in the quality of bowel preparation compared with the PEG-placebo group including colon cleanliness in interval P-C at 8 and 9 h (p<0.05) and bubble elimination in interval P-C at 5, 6, 7, 8, and 9 h (p<0.05). Compared with the PEG-placebo group, the ADR (23.3% vs. 15.0%, p<0.05) and the size (≤5 mm) of the adenoma (45.2% vs. 18.5%, p<0.05) increased in the PEG-lactulose group, and there were significant differences between the two groups. CONCLUSION: PEG solution combined with lactulose can improve the quality of colonoscopy in patients with long interval P-C to allow the patients to select more flexible colonoscopy time. It is worth further popularizing in clinical practice.

THE IMPACT OF SMALL INTESTINAL BACTERIAL OVERGROWTH ON THE GROWTH OF CHILDREN AND ADOLESCENTS.

OBJECTIVE: To evaluate the association between small intestinal bacterial overgrowth (SIBO) and weight and height impairment in children and adolescents with gastroenterology diseases. METHODS: Observational and retrospective study. All 162 patients aged less than 19 years old who underwent breath test in search of SIBO between 2011 and 2016 were studied. Breath test was collected after the intake of 10 grams of lactulose. The concentration of hydrogen and methane was measured for 180 minutes after the beginning of the test by 12i QuinTronMicroLyzer device. RESULTS: SIBO was identified in 51 (31.5%) patients. There was no difference between the age of those with (mean=8.7y.o; 25th and 75th percentile: 4.6 and 11.3) and without (mean=7.9y.o 25th and 75th percentile: 4.8 and 12.2) SIBO (p=0.910). There was no association between gender and SIBO (male 26.3% vs. female 36.3%, p=1.00). A lower median of height-for-age Z score (mean=-1.32; 25th and 75th percentile: -2.12 and -0.08 vs. mean=-0.59; 25th and 75th percentile: -1.57 and 0.22; p=0.04) was demonstrated in children with SIBO when compared with children without it. There was no difference between the BMI-for-age Z score of patients with (mean=-0.48) and without SIBO (mean=-0.06) (p=0.106). The BMI of patients with SIBO (median=15.39) was lower than of those without it (median=16.06); however, the statistical analysis was not significant (p=0.052). The weight-for-age Z score was lower in patients with SIBO (mean=-0.96) than in those without SIBO (mean=-0.22) (p=0.02). CONCLUSIONS: Children and adolescents with SBIO associated with diseases of the gastrointestinal tract have lower weight and height values.

Effects of early detection of peritoneal catheter migration on clinical outcomes: 15-years experiences from a single centre.

AIM: Catheter migration is an important cause of catheter malfunction in peritoneal dialysis (PD). The purpose of this study was to investigate the effect of early detection of catheter migration on clinical outcomes. METHODS: A retrospective review of 135 consecutive patients initiating PD immediately following catheter insertion from 2002 to 2017 was undertaken. In order to detect catheter migration without malfunction early, serial abdominal-pelvic radiographic examinations were performed according to a predefined protocol. Conservative management with rigorous catharsis was undertaken to correct catheter migration. A Kaplan-Meier method was used to calculate survival rate. RESULTS: Mean follow-up period was 42.8 ± 34.9 months. Catheter migration occurred in 62.4%. Among them, 85.9% occurred within the first 2 weeks after catheter insertion. There were no significant associations between catheter migration and variables such as gender, obesity, DM and type of catheter. Success rate of conservative management with rigorous catharsis was 91.1%. Catheter survival at 1 and 5 years were 91.5% and 64.6% in the migration group and 81.2% and 69.9% in the non-migration group, respectively (Log-rank test, P = 0.915). Patient survival at 1 and 5 years were 96.8% and 85.8% in the migration group and 91.9% and 82.3% in the non-migration group, respectively (P = 0.792). CONCLUSION: Early detection of PD catheter migration allowed the migrated tip to be easily corrected with conservative management. Once the migrated catheter tip was restored, catheter migration itself did not affect catheter survival. These findings suggest that early detection and correction of catheter migration is important for improving clinical outcomes.

Intestinal microbiome analysis demonstrates azithromycin post-treatment effects improve when combined with lactulose.

BACKGROUND: Next-generation sequencing has revolutionized our perspective on the gut microbiome composition, revealing the true extent of the adverse effects of antibiotics. The impact of antibiotic treatment on gut microbiota must be considered and researched to provide grounds for establishing new treatment strategies that are less devastating on commensal bacteria. This study investigates the impact on gut microbiome when a commonly used antibiotic, azithromycin is administered, as well as uncovers the benefits induced when it is used in combination with lactulose, a prebiotic known to enhance the proliferation of commensal microbes. METHODS: 16S rRNA gene sequencing analysis of stool samples obtained from 87 children treated with azithromycin in combination with or without lactulose have been determined. Children's gut microbial profile was established at the pre- and post-treatment stage. RESULTS: Azithromycin caused an increase in the relative abundance of opportunistic pathogens such as Streptococcus that was evident 60 days after treatment. While few days after treatment, children who also received lactulose started to show a higher relative abundance of saccharolytic bacteria such as Lactobacillus, Enterococcus, Anaerostipes, Blautia and Roseburia, providing a protective role against opportunistic pathogens. In addition, azithromycin-prebiotic combination was able to provide a phylogenetic profile more similar to the pre-treatment stage. CONCLUSION: It is suggested that during azithromycin treatment, lactulose is able to reinstate the microbiome equilibrium much faster as it promotes saccharolytic microbes and provides a homeostatic effect that minimizes the opportunistic pathogen colonization.

The impact of small intestinal bacterial overgrowth on the growth of children and adolescents / Impacto do sobrecrescimento bacteriano no intestino delgado sobre o peso e a estatura de crianças e adolescentes

ABSTRACT Objective: To evaluate the association between small intestinal bacterial overgrowth (SIBO) and weight and height impairment in children and adolescents with gastroenterology diseases. Methods: Observational and retrospective study. All 162 patients aged less than 19 years old who underwent breath test in search of SIBO between 2011 and 2016 were studied. Breath test was collected after the intake of 10 grams of lactulose. The concentration of hydrogen and methane was measured for 180 minutes after the beginning of the test by 12i QuinTronMicroLyzer device. Results: SIBO was identified in 51 (31.5%) patients. There was no difference between the age of those with (mean=8.7y.o; 25th and 75th percentile: 4.6 and 11.3) and without (mean=7.9y.o 25th and 75th percentile: 4.8 and 12.2) SIBO (p=0.910). There was no association between gender and SIBO (male 26.3% vs. female 36.3%, p=1.00). A lower median of height-for-age Z score (mean=-1.32; 25th and 75th percentile: -2.12 and -0.08 vs. mean=-0.59; 25th and 75th percentile: -1.57 and 0.22; p=0.04) was demonstrated in children with SIBO when compared with children without it. There was no difference between the BMI-for-age Z score of patients with (mean=-0.48) and without SIBO (mean=-0.06) (p=0.106). The BMI of patients with SIBO (median=15.39) was lower than of those without it (median=16.06); however, the statistical analysis was not significant (p=0.052). The weight-for-age Z score was lower in patients with SIBO (mean=-0.96) than in those without SIBO (mean=-0.22) (p=0.02) Conclusions: Children and adolescents with SBIO associated with diseases of the gastrointestinal tract have lower weight and height values.

RESUMO Objetivo: Avaliar a existência de associação entre sobrecrescimento bacteriano no intestino delgado (SBID) e comprometimento de peso e estatura em crianças e adolescentes com doenças do aparelho digestivo. Métodos: Estudo observacional e retrospectivo em ambulatório de gastroenterologia pediátrica. Foram incluídos todos os 162 pacientes com idade inferior a 19 anos que realizaram teste respiratório para pesquisa de SBID entre 2011 e 2016. O teste respiratório foi realizado após ingestão de dez gramas de lactulose. Foram determinadas as concentrações de hidrogênio e metano em aparelho 12i QuinTron MicroLyzer até 180 minutos após o início do teste respiratório. Resultados: SBID foi caracterizado em 51 (31,5%) dos 162 pacientes. Não houve diferença na idade das crianças com (mediana=8,7 anos; percentil 25-75: 4,6-11,3) e sem (mediana=7,9 anos; percentil 25-75: 4,8-12,2) SBID (p=0,910). Não se observou associação entre SBID e sexo (masculino 27,4% e feminino 36,6%; p=0,283). O escore Z da estatura-idade nos pacientes com SBID (mediana=-1,32; percentil 25-75: -2,12—0,08) foi menor (p=0,040) do que naqueles sem SBID (mediana=-0,59; percentil 25-75: -1,57-0,22). Na comparação do escore Z de índice de massa corpórea-idade não foi observada diferença entre os grupos com (média=-0,489±1,528) e sem (média=-0,067±1,532) SBID (p=0,106). Nos pacientes com menos de 10 anos de idade, o escore Z de peso-idade foi menor nos pacientes com SBID (média=-0,968±1,359) do que nos sem SBID (média=-0,223±1,584) (p=0,026). Conclusões: Crianças e adolescentes com SBID associado a doenças do trato gastrintestinal apresentam menores valores de peso e estatura.

Metabolic encephalopathy caused by nitrous oxide ('laughing gas') induced hyperammonaemia.

A 26-year-old man presented at the emergency department with confusion and decreased consciousness after several days of vomiting. In the preceding 6 months, he had used a 2-litre tank of nitrous oxide (N2O) weekly. His metabolic encephalopathy was caused by hyperammonaemia which probably resulted from interference of N2O-induced vitamin B12 deficiency with ammonia degradation. A catabolic state might have contributed to the hyperammonaemia in this case. After treatment with vitamin B12 and lactulose, both his consciousness and hyperammonaemia improved. He reported no residual complaints after 3 months of follow-up. Since N2O is increasingly used as a recreational drug, we recommend considering hyperammonaemia as a cause of metabolic encephalopathy in cases of N2O use and altered mental status.

Small intestinal bacterial overgrowth: could it be associated with chronic abdominal pain in children with allergic diseases?

BACKGROUND AND AIMS: small intestinal bacterial overgrowth (SIBO) is a well-known cause of chronic abdominal pain (CAP) during the pediatric age. On the other hand, children with a history of some allergic disorder present CAP more frequently. The aim of this study was to determine the association between the presence of allergic diseases and SIBO in patients diagnosed with CAP. MATERIALS AND METHODS: this was an observational, analytical, retrospective study. Children with CAP who had undergone a lactulose hydrogen breath test to determine the presence of SIBO were included in the study. All patients underwent an evaluation for allergies by means of a skin prick test or the determination of specific IgE, according to clinical diagnosis. The study groups were established according to the presence of SIBO and the results of the allergic evaluation were statistically compared between the groups. RESULTS: seventy patients were included (41 females and 29 males) and SIBO was diagnosed in 35 patients. In addition, 71.4% of children with SIBO were found to have an allergic disease, in contrast with 28.6% of children without SIBO (p = 0.001). The odds ratio for having any type of allergy in patients with SIBO was 5.45 (95% CI, 1.96-15.17; p = 0.001). CONCLUSIONS: we found an association between SIBO and allergic disease, especially allergic rhinitis, cow's milk protein allergy and asthma. Thus, SIBO should be ruled out in pediatric patients with CAP and allergic disease.

Measurement of intestinal permeability using lactulose and mannitol with conventional five hours and shortened two hours urine collection by two different methods: HPAE-PAD and LC-MSMS.

Urinary excretion of two orally-administered non-metabolizable sugars, lactulose and mannitol, is a valuable marker for evaluating intestinal permeability. Usually this test involves a time consuming procedure of about 5 hour's urine collection, which makes the test incompatible to some extent. As the results are expressed as the ratio of lactulose and mannitol recovered in urine within certain time, it may be possible to get similar result despite the reduced urine collection time of 2 hours. Moreover, different laboratories do the test by different methods, which make the results incomparable between laboratories. Here, we are also trying to find the correlation between results from most commonly used methods: HPAE-PAD and LC-MSMS. The lactulose: mannitol (LM) test was performed in a cohort of Bangladeshi infants considered at-risk for environmental enteropathy. 208 urine specimens from 104 (52 male and 52 female) infants were collected at 2 and 5 hours after LM solution administration and were tested for lactulose and mannitol by two different methods, one HPAE-PAD platform and another LC-MSMS platform. Median age of the children was 15.0 months (range 6.9 to 25.8 months) and their mean weight-for-age z-score was -0.92. A higher percentage of lactulose and mannitol recovery was found in 5 hours urine collection than in the corresponding 2 hours by both HPAE-PAD and LC-MSMS method, but when results were expressed as lactulose to mannitol ratio (LMR) there was no significant difference between 2 and 5 hours urine collection in both HPAE-PAD (P = 0.138) and LC-MSMS (P = 0.099) method. LMR based on 2 hours urine collection correlated well with LMR based on traditional 5 hours urine collection (Spearman's correlation coefficient 0.578 and 0.604 respectively for HPAE-PAD and LC-MSMS). In future, LM test to assess intestinal permeability in children can be simplified by shortening the urine collection time from 5 hours to 2 hours.