Developmental changes and fructose absorption in children: effect on malabsorption testing and dietary management.

Fructose malabsorption came to prominence in the pediatric arena as so-called "apple juice diarrhea," with excess consumption of fructose being linked to gastrointestinal symptoms such as diarrhea and abdominal pain. Over the past two decades the amount of fructose in children's diets has been increasing in the United States. A test for fructose malabsorption has yet to be fully validated, due mainly to the lack of an established etiology. In animal models, however, the fructose transporter GLUT5 is developmentally regulated, and this could be consistent with the greater susceptibility of children, especially toddlers, to fructose malabsorption. Additionally, the available evidence indicates the fructose breath hydrogen test has no apparent diagnostic utility in infants younger than 1 year; it may, therefore, be advisable to test for malabsorption by dietary exclusion in these patients. The present review aims to expound on the biological basis for fructose malabsorption in children and evaluate the current evidence for diagnostic procedures in order to identify clinical testing strategies that can be recommended and areas where further investigation is required.

A role for altered phagosome maturation in the long-term persistence of Helicobacter pylori infection.

The vigorous host immune response that is mounted against Helicobacter pylori is unable to eliminate this pathogenic bacterium from its niche in the human gastric mucosa. This results in chronic inflammation, which can develop into gastric or duodenal ulcers in 10% of infected individuals and gastric cancer in 1% of infections. The determinants for these more severe pathologies include host (e.g., high IL-1ß expression polymorphisms), bacterial [e.g., cytotoxicity-associated gene (cag) pathogenicity island], and environmental (e.g., dietary nitrites) factors. However, it is the failure of host immune effector cells to eliminate H. pylori that underlies its persistence and the subsequent H. pylori-associated disease. Here we discuss the mechanisms used by H. pylori to survive the host immune response and, in particular, the role played by altered phagosome maturation.

Effect of age on fructose malabsorption in children presenting with gastrointestinal symptoms.

OBJECTIVES: Fructose malabsorption can produce symptoms such as chronic diarrhoea and abdominal pain. Here, we retrospectively review breath hydrogen test (BHT) results to determine whether age has an effect on the clinical application of the fructose BHT and compare this with the lactose BHT. PATIENTS AND METHODS: Patients were referred to a gastroenterology breath-testing clinic (2003-2008) to investigate carbohydrate malabsorption as a cause of gastrointestinal symptoms. Patients received either 0.5 g/kg body weight of fructose (maximum of 10 g) or 2 g/kg of lactose (maximum of 20 g), in water, and were tested for 2.5 hours. RESULTS: Patient age showed a significant effect on the fructose BHT results (P < 0.001, 0.1-79 years old, n = 1093). The odds of testing positive for fructose malabsorption in paediatric patients (15 years old or younger, n = 760) decreased by a factor of 0.82/year (95% confidence interval 0.79-0.86, P < 0.001). There were 88.2% positive in younger than 1-year-olds, 66.6% in 1- to 5-year-olds, 40.4% in 6- to 10-year-olds, and 27.1% in 10- to 15-year-olds. In contrast, 39.3% of lactose BHTs were positive, with no significant relation between patient age and test result (P = 0.115, 0.1-89 years old, n = 3073). CONCLUSIONS: The majority of infants with gastrointestinal symptoms exhibited fructose malabsorption, but the capacity to absorb fructose increased with patient age up to 10 years old. The low threshold for fructose absorption in younger children has significant implications for the performance and interpretation of the fructose BHT and for the dietary consumption of fructose in infants with gastrointestinal symptoms.

Is small-bowel bacterial overgrowth an underdiagnosed disorder in children with gastrointestinal symptoms?

Small-bowel bacterial overgrowth (SBBO) has been implicated in chronic abdominal pain and irritable bowel syndrome in children. This was a retrospective study that aimed to assess the occurrence of SBBO by the lactulose breath hydrogen test in children referred primarily for investigation of carbohydrate malabsorption (n = 287). There were profiles indicative of SBBO in 16% (39/250) of hydrogen-producing children. This indicated that SBBO may be more common in children with gastrointestinal symptoms and apparent carbohydrate malabsorption than previously recognised.

Helicobacter pylori phagosome maturation in primary human macrophages.

BACKGROUND: Helicobacter pylori (H. pylori) is a micro-aerophilic, spiral-shaped, motile bacterium that is the principal cause of gastric and duodenal ulcers in humans and is a major risk factor for the development of gastric cancer. Despite provoking a strong innate and adaptive immune response in the host, H. pylori persists in the gastric mucosa, avoiding eradication by macrophages and other phagocytic cells, which are recruited to the site of infection. Here we have characterised the critical degradative process of phagosome maturation in primary human macrophages for five genotypically and phenotypically distinct clinical strains of H. pylori. RESULTS: All of the H. pylori strains examined showed some disruption to the phagosome maturation process, when compared to control E. coli. The early endosome marker EEA1 and late endosome marker Rab7 were retained on H. pylori phagosomes, while the late endosome-lysosome markers CD63, LAMP-1 and LAMP-2 were acquired in an apparently normal manner. Acquisition of EEA1 by H. pylori phagosomes appeared to occur by two distinct, strain specific modes. H. pylori strains that were negative for the cancer associated virulence factor CagA were detected in phagosomes that recruited large amounts of EEA1 relative to Rab5, compared to CagA positive strains. There were also strain specific differences in the timing of Rab7 acquisition which correlated with differences in the rate of intracellular trafficking of phagosomes and the timing of megasome formation. Megasomes were observed for all of the H. pylori strains examined. CONCLUSIONS: H. pylori appeared to disrupt the normal process of phagosome maturation in primary human macrophages, appearing to block endosome fission. This resulted in the formation of a hybrid phagosome-endosome-lysosome compartment, which we propose has reduced degradative capacity. Reduced killing by phagocytes is consistent with the persistence of H. pylori in the host, and would contribute to the chronic stimulation of the inflammatory immune response, which underlies H. pylori-associated disease.

Intestinal fructose transport and malabsorption in humans.

Fructose is a hexose sugar that is being increasingly consumed in its monosaccharide form. Patients who exhibit fructose malabsorption can present with gastrointestinal symptoms that include chronic diarrhea and abdominal pain. However, with no clearly established gastrointestinal mechanism for fructose malabsorption, patient analysis by the proxy of a breath hydrogen test (BHT) is controversial. The major transporter for fructose in intestinal epithelial cells is thought to be the facilitative transporter GLUT5. Consistent with a facilitative transport system, we show here by analysis of past studies on healthy adults that there is a significant relationship between fructose malabsorption and fructose dose (r = 0.86, P < 0.001). Thus there is a dose-dependent and limited absorption capacity even in healthy individuals. Changes in fructose malabsorption with age have been observed in human infants, and this may parallel the developmental regulation of GLUT5 expression. Moreover, a GLUT5 knockout mouse has displayed the hallmarks associated with profound fructose malabsorption. Fructose malabsorption appears to be partially modulated by the amount of glucose ingested. Although solvent drag and passive diffusion have been proposed to explain the effect of glucose on fructose malabsorption, this could possibly be a result of the facilitative transporter GLUT2. GLUT5 and GLUT2 mRNA have been shown to be rapidly upregulated by the presence of fructose and GLUT2 mRNA is also upregulated by glucose, but in humans the distribution and role of GLUT2 in the brush border membrane are yet to be definitively decided. Understanding the relative roles of these transporters in humans will be crucial for establishing a mechanistic basis for fructose malabsorption in gastrointestinal patients.