Circulating Dipeptidyl Peptidase Activity Is a Potential Biomarker for Inflammatory Bowel Disease.

INTRODUCTION: Dipeptidyl peptidase (DPP)-4 is part of a larger family of proteases referred to as DPPs. DPP4 has been suggested as a possible biomarker for inflammatory bowel disease (IBD). Circulating DPP4 (cDPP4) enzyme activity was investigated as a potential biomarker for IBD. In addition, DPP enzyme activity and gene expression were quantified in colonic tissue of patients with IBD and non-IBD. METHODS: In study 1, DPP enzyme activity was quantified in plasma samples from 220 patients with IBD (Crohn's disease [CD] n = 130 and ulcerative colitis [UC] n = 90) and non-IBD controls (n = 26) using a colorimetric assay. In study 2, tissue and plasma samples were collected from 26 patients with IBD and 20 non-IBD controls. Plasma C-reactive protein (CRP) was quantified in all patients. Colonic DPP4, DPP8, DPP9, and fibroblast activation protein (FAP) gene expression was determined by quantitative polymerase chain reaction. cDPP and cFAP enzyme activity was also measured. Sensitivity and specificity were determined by receiver operating characteristic curve analysis. RESULTS: In study 1, total cDPP activity was found to differentiate patients with CD with active disease (n = 18) from those in remission (n = 19; sensitivity 78% and specificity 63%). In study 2, total cDPP and cFAP activity was 28% and 48% lower in patients with elevated CRP (>10 mg/L), respectively, compared with patients with normal CRP. Gene expression of DPP4, FAP, and DPP8 was also significantly higher in colonic biopsies from patients with IBD compared with non-IBD patients (P < 0.05). DISCUSSION: Our findings implicate the DPP enzyme family in intestinal inflammation and suggest future biomarker applications to differentiate the pathophysiological aspects of IBD.

Breath 13CO2-evidence for a noninvasive biomarker to measure added refined sugar uptake.

Increased consumption of added sucrose and high-fructose corn syrup in the human diet has been associated with increasing incidence of obesity and metabolic disease. There are currently no reliable, objective biomarkers for added sugar intake that could be used in individuals or population settings. 13C is a stable isotope of carbon, and measurement of blood 13C content has been proposed as a marker of added sugar consumption. This study aimed to determine if breath 13CO2 could represent an alternative, noninvasive biomarker to monitor added sugar intake. We undertook retrospective analyses of eight preclinical and human 13C-breath studies to define baseline breath 13CO2 characteristics. All samples were analyzed using isotope ratio mass spectrometry, and breath 13CO2 was expressed as the delta value, δ expressed as parts per thousand (‰). All data are expressed as mean ± SEM, with statistical significance considered at P < 0.05. Breath δ13CO2 was significantly elevated in a cumulative manner in rats and mice that consumed a diet containing at least 15% sucrose. Mice fed an American rodent chow diet containing 50% sucrose and 15% corn starch had a significantly higher breath δ13CO2 compared with rodents consuming an Australian rodent chow diet. Furthermore, breath δ13CO2 was significantly increased in a dose-dependent manner in humans that ingested a bolus dose of sucrose. These findings suggest application for baseline breath δ13CO2 as a noninvasive biomarker for added sugar consumption, with broad application for longitudinal assessment of population sugar intake and obesity management strategies.NEW & NOTEWORTHY We have found that breath 13CO2 is increased in rats and mice consuming diets high in sucrose. We also found that human breath 13CO2 is increased in humans consuming increasing amounts of sucrose. Our collective findings suggest that breath 13CO2 represents a potential marker of added dietary sugar consumption.

Prebiotics Fructo-, Galacto-, and Mannan-Oligosaccharide Do Not Protect against 5-Fluorouracil-Induced Intestinal Mucositis in Rats.

BACKGROUND: Prebiotics selectively stimulate the growth of beneficial bacteria within the gastrointestinal tract, and have been investigated in human and animal studies for their capacity to improve intestinal health. OBJECTIVE: We investigated the prebiotics fructo-oligosaccharide (FOS), galacto-oligosaccharide (GOS), and mannan-oligosaccharide (MOS) for their potential to alleviate intestinal damage in rats. METHODS: Female Dark Agouti rats (6-8 wk old, 110-150 g) were allocated to 1 of the following treatment groups (n = 8/group): saline/water, saline/FOS, saline/GOS, saline/MOS, 5-fluorouracil (5FU)/water, 5FU/FOS, 5FU/GOS, and 5FU/MOS. Rats were pretreated with either 5% GOS, MOS, or FOS or vehicle (water) from day -12 to day 0. On day 0, rats received a single intraperitoneal injection of saline or 5FU. Metabolic data were recorded daily and all rats were killed on day 3. Histopathology was quantified in hematoxylin and eosin-stained sections. Intestinal sucrase and myeloperoxidase activity were quantified by biochemical assay. Fecal SCFAs-acetic, propionic, and butyric acid-were also measured. Statistical analysis was by repeated-measures, 2-factor ANOVA or Kruskal-Wallis and Mann-Whitney U test; P < 0.05 was considered statistically significant. RESULTS: Body weight was significantly decreased in all treatment groups after 5FU injection, with no change in body weight observed in any prebiotic treatment group. Total food intake was lower by ≥7% in the GOS treatment group pre-5FU than in all other groups (P < 0.05). Ileal villus height was 18% higher in GOS-treated rats pre-5FU than in respective water controls (P < 0.05). Jejunal and ileal villus height and crypt depth were significantly decreased in all treatment groups after 5FU injection, with no prebiotic effect observed. SCFAs were differentially increased in prebiotic treatment groups compared with water-only controls (P < 0.05). CONCLUSIONS: FOS, GOS, and MOS have differential effects in modifying small intestinal pathology and SCFA profiles in rats with healthy and damaged small intestinal mucosa.

Development of a 13C Stable Isotope Assay for Dipeptidyl Peptidase-4 Enzyme Activity A New Breath Test for Dipeptidyl Peptidase Activity.

Dipeptidyl peptidase-4 inhibitors (DPP4i) are a class of orally available, small molecule inhibitors for the management of Type-II diabetes. A rapid, real-time, functional breath test for DPP4 enzyme activity could help to define DPP4i efficacy in patients that are refractory to treatment. We aimed to develop a selective, non-invasive, stable-isotope 13C-breath test for DPP4. In vitro experiments were performed using high (Caco-2) and low (HeLa) DPP4 expressing cells. DPP gene expression was determined in cell lines by qRT-PCR. A DPP4 selective 13C-tripeptide was added to cells in the presence and absence of the DPP4 inhibitor Sitagliptin. Gas samples were collected from the cell headspace and 13CO2 content quantified by isotope ratio mass spectrometry (IRMS). DPP4 was highly expressed in Caco-2 cells compared to HeLa cells and using the 13C-tripeptide, we detected a high 13CO2 signal from Caco2 cells. Addition of Sitaglitpin to Caco2 cells significantly inhibited this 13CO2 signal. 13C-assay DPP4 activity correlated positively with the enzyme activity detected using a colorimetric substrate. We have developed a selective, non-invasive, 13C-assay for DPP4 that could have broad translational applications in diabetes and gastrointestinal disease.

Stable Isotope Techniques for the Assessment of Host and Microbiota Response During Gastrointestinal Dysfunction.

The International Atomic Energy Agency convened a technical meeting on environmental enteric dysfunction (EED) in Vienna (October 28-30, 2015; https://nucleus.iaea.org/HHW/Nutrition/EED_Technical_Meeting/index.html) to bring together international experts in the fields of EED, nutrition, and stable isotope technologies. Advances in stable isotope-labeling techniques open up new possibilities to improve our understanding of gastrointestinal dysfunction and the role of the microbiota in host health. In the context of EED, little is known about the role gut dysfunction may play in macro- and micronutrient bioavailability and requirements and what the consequences may be for nutritional status and linear growth. Stable isotope labeling techniques have been used to assess intestinal mucosal injury and barrier function, carbohydrate digestion and fermentation, protein-derived amino acid bioavailability and requirements, micronutrient bioavailability and to track microbe-microbe and microbe-host interactions at the single cell level. The noninvasive nature of stable isotope technologies potentially allow for low-hazard, field-deployable tests of gut dysfunction that are applicable across all age groups. The purpose of this review is to assess the state-of-the-art use of stable isotope technologies and to provide a perspective on where these technologies can be exploited to further our understanding of gut dysfunction in EED.

A simple and inexpensive enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine.

Understanding the ecology of the gastrointestinal tract and the impact of the contents on the host mucosa is emerging as an important area for defining both wellness and susceptibility to disease. Targeted delivery of drugs to treat specific small intestinal disorders such as small bowel bacterial overgrowth and targeting molecules to interrogate or to deliver vaccines to the remote regions of the small intestine has proven difficult. There is an unmet need for methodologies to release probes/drugs to remote regions of the gastrointestinal tract in furthering our understanding of gut health and pathogenesis. In order to address this concern, we need to know how the regional delivery of a surrogate labeled test compound is handled and in turn, if delivered locally as a liquid or powder, the dynamics of its subsequent handling and metabolism. In the studies we report on in this paper, we chose (13)C sodium acetate ((13)C-acetate), which is a stable isotope probe that once absorbed in the small intestine can be readily measured non-invasively by collection and analysis of (13)CO2 in the breath. This would provide information of gastric emptying rates and an indication of the site of release and absorptive capacity. In a series of in vitro and in vivo pig experiments, we assessed the enteric-protective properties of a commercially available polymer EUDRAGIT(®) L100-55 on gelatin capsules and also on DRcaps(®). Test results demonstrated that DRcaps(®) coated with EUDRAGIT(®) L100-55 possessed enhanced enteric-protective properties, particularly in vivo. These studies add to the body of knowledge regarding gastric emptying in pigs and also begin the process of gathering specifications for the design of a simple and cost-effective enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine.

Zinc-fortified oral rehydration solution improved intestinal permeability and small intestinal mucosal recovery.

A randomized double-blind placebo-controlled study was conducted in children admitted to hospital with gastroenteritis (≥3 loose stools per day). All were treated for 5 days following admission with either zinc (Zn, 3 mg) or without Zn-fortified rice-based oral rehydration solution (ORS). (13)C-sucrose breath test (SBT) and intestinal permeability (lactulose/rhamnose or L/R ratio) were performed concurrently prior to commencement of ORS with or without Zn and at day 5 post-admission. There was a significant improvement in the SBT results in both the Zn-fortified group, median (5th-95th percentile) 2.1% (0.4% to 8.3%) versus 4.4% (0.4% to 10.4%), P < .05, and control group, 1.4% (0.1% to 5.4%) versus 4.3% (0.4% to 11.4%), P < .05, between the day of admission and day 5 post-admission. In the Zn-fortified group, there was also a significant improvement in L/R ratio between the day of admission and day 5 post-admission, 53.0 (19.5-90.6) versus 17.7 (13.4-83.2), P < .05. Low levels of Zn improved intestinal permeability but did not enhance short-term recovery following diarrheal illness.

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.

Probiotic factors partially prevent changes to caspases 3 and 7 activation and transepithelial electrical resistance in a model of 5-fluorouracil-induced epithelial cell damage.

The potential efficacy of a probiotic-based preventative strategy against intestinal mucositis has yet to be investigated in detail. We evaluated supernatants (SN) from Escherichia coli Nissle 1917 (EcN) and Lactobacillus rhamnosus GG (LGG) for their capacity to prevent 5-fluorouracil (5-FU)-induced damage to intestinal epithelial cells. A 5-day study was performed. IEC-6 cells were treated daily from days 0 to 3, with 1 mL of PBS (untreated control), de Man Rogosa Sharpe (MRS) broth, tryptone soy roth (TSB), LGG SN, or EcN SN. With the exception of the untreated control cells, all groups were treated with 5-FU (5 µM) for 24 h at day 3. Transepithelial electrical resistance (TEER) was determined on days 3, 4, and 5, while activation of caspases 3 and 7 was determined on days 4 and 5 to assess apoptosis. Pretreatment with LGG SN increased TEER (p < 0.05) compared to controls at day 3. 5-FU administration reduced TEER compared to untreated cells on days 4 and 5. Pretreatment with MRS, LGG SN, TSB, and EcN SN partially prevented the decrease in TEER induced by 5-FU on day 4, while EcN SN also improved TEER compared to its TSB vehicle control. These differences were also observed at day 5, along with significant improvements in TEER in cells treated with LGG and EcN SN compared to healthy controls. 5-FU increased caspase activity on days 4 and 5 compared to controls. At day 4, cells pretreated with MRS, TSB, LGG SN, or EcN SN all displayed reduced caspase activity compared to 5-FU controls, while both SN groups had significantly lower caspase activity than their respective vehicle controls. Caspase activity in cells pretreated with MRS, LGG SN, and EcN SN was also reduced at day 5, compared to 5-FU controls. We conclude that pretreatment with selected probiotic SN could prevent or inhibit enterocyte apoptosis and loss of intestinal barrier function induced by 5-FU, potentially forming the basis of a preventative treatment modality for mucositis.

Short-chain fatty acids induce apoptosis in colon cancer cells associated with changes to intracellular redox state and glucose metabolism.

BACKGROUND: Short-chain fatty acids (SCFA) are undergoing increased scrutiny as chemotherapeutics for colon cancer, although a comprehensive understanding of their mode of action is lacking. We investigated candidate SCFA for their capability to modulate apoptosis, cell cycle, intracellular redox state and glucose metabolism in the Caco-2 human colon cancer cell line. METHODS: Caco-2 cells were incubated with butyrate, propionate or a combination of these SCFA (1:1) and assessed by flow cytometry, enzyme activity analysis or by isotope ratio mass spectrometry. RESULTS: Butyrate and the SCFA combination induced apoptosis and G2-M arrest to a greater extent than propionate alone (p < 0.05). SCFA treatment led to time-dependent alterations to the oxidative pentose pathway, reductions in glutathione availability and increases in levels of reactive oxygen species (p < 0.05) compared with untreated controls. The rate of D-glucose metabolism was increased by all SCFA, although to the greatest extent by butyrate (p < 0.05). CONCLUSIONS: These results suggest that butyrate, or the combination of both SCFA, induced rapid and extensive apoptosis and G2-M arrest associated with changes to redox state and D-glucose metabolism. These results support the potential for butyrate and propionate to act as adjuncts to conventional chemotherapy regimens for colon cancer.

Emu oil increases colonic crypt depth in a rat model of ulcerative colitis.

BACKGROUND: Current treatments for the inflammatory bowel diseases, encompassing Crohn's disease and ulcerative colitis, are variably effective. Emu oil, extracted from emu fat, predominantly comprises fatty acids, with purported claims of anti-inflammatory properties. AIM: We evaluated emu oil for its potential to ameliorate dextran sulphate sodium (DSS)-induced colitis in rats. METHODS: Male Sprague-Dawley Rats were allocated to treatment groups (n = 8). Groups 1 and 2 consumed water and were gavaged (1 ml) daily with water (group 1) or emu oil (group 2) from days 0 to 10. Groups 3-6 ingested 2% DSS in the drinking water from days 5 to 10 and were gavaged from days 0 to 10 with water (group 3), 0.5 ml emu oil (group 4) or 1 ml emu oil (group 5). Group 6 received 1 ml emu oil after commencing DSS treatment (days 6-10). Disease activity index, metabolic parameters, (13)C-sucrose breath test, and histological colonic damage severity and crypt depth were assessed. RESULTS: Emu oil in DSS-treated rats reduced colonic damage severity compared to DSS-controls (up to threefold; P < 0.001). In DSS-treated rats, crypts in the proximal colon were lengthened by 0.5 ml emu oil (373 ± 18 µm), compared with DSS-controls (302 ± 8 µm); whilst in the distal colon (DSS control: 271 ± 17 µm), crypt depth was greater following 0.5 ml emu oil (352 ± 22 µm) and 1 ml emu oil (341 ± 9 µm) and also when emu oil was administered post-DSS commencement (Group 6: 409 ± 16 µm; P < 0.05). Emu oil did not significantly affect other parameters of colonic architecture. CONCLUSIONS: Emu oil improved tissue damage associated with colitis, suggesting its potential as a unique formulation to augment conventional treatment approaches for IBD.

Zinc homeostasis and gut function in children with celiac disease.

BACKGROUND: Celiac disease (CD) is an immunologic enteropathy triggered by the intake of gluten. It is thought that the enteropathy impairs gut function and absorption. OBJECTIVE: We assessed the zinc-absorption capacity and small-bowel integrity in children with CD. DESIGN: Children in whom a diagnosis of CD was considered clinically and either confirmed (n = 16; Marsh score ≥3) or not (n = 22; Marsh score of 0) with a small-bowel biopsy (SBB) were recruited. The fractional absorption of zinc (FAZ) was determined by the administration of an oral (67)Zn dose (2.5 mg) and an intravenous (70)Zn dose (0.2 mg) 2 h before and during the SBB, respectively. Spot urine samples were collected, and zinc isotopic ratios were determined by ion-coupled plasma mass spectrometry. Gut health was assessed by the ingestion of (13)C-sucrose (20 g) after an overnight fast, and breath samples were collected and analyzed by isotope ratio mass spectrometry. RESULTS: There was no difference in FAZ between children with a Marsh score ≥3 (mean ± SEM: 0.68 ± 0.05) and children with a Marsh score of 0 (0.74 ± 0.05). The exchangeable zinc pool (EZP) was significantly (P < 0.05) lower in children with a Marsh score ≥3 (2.6 ± 0.8 mg/kg) than in children with a Marsh score of 0 (3.8 ± 1.4 mg/kg). Gut function in children with a Marsh score ≥3 (4.5 ± 0.7% cumulative dose recovered at 90 min) was lower than the lower cutoff of a normal gut-function breath test (5.06% cumulative dose recovered at 90 min) but not significantly different from that in children with a Marsh score of 0 (4.9 ± 0.4%). There was a significant (P < 0.01) correlation between zinc absorption and gut function in children with CD. CONCLUSIONS: Zinc absorption did not appear below usual amounts in subjects with CD. Children with CD have impaired gut function that may affect their zinc nutritional status as shown by a smaller EZP. However, the EZP decrease in children with CD was not compared with that in healthy control subjects, and its biological meaning is uncertain.

Non-invasive detection of a palifermin-mediated adaptive response following chemotherapy-induced damage to the distal small intestine of rats.

INTRODUCTION: Pre-clinical studies have indicated that palifermin may be an effective treatment modality for intestinal mucositis, a debilitating complication of cancer chemotherapy. We determined whether palifermin was protective in rats with experimentally induced intestinal mucositis and the applicability of the sucrose breath test (SBT) to monitor palifermin for its efficacy as an anti-mucositis agent. RESULTS: SBT values and sucrase activity were reduced in all 5-FU-treated groups compared with untreated controls (p < 0.05). At 72 h post 5-FU, sucrase activity was higher in rats treated with palifermin compared with 5-FU controls (p < 0.05). Jejunal and ileal villus heights were lower in all 5-FU groups compared with saline controls. METHODS: Dark agouti rats (n = 10) were subcutaneously injected with palifermin or vehicle for 3 d after which they were injected with 5-fluorouracil (5-FU) and sacrificed after 72 h. The in vivo SBT and in vitro sucrase assay were used to evaluate small intestinal function and damage. Intestinal disease severity was determined by histological assessment of villus height and crypt depth. CONCLUSION: The SBT can monitor the ability of palifermin to modify the functional capacity of the small intestine in rats with intestinal mucositis. Further studies are indicated to investigate the prophylactic potential of palifermin against intestinal mucositis.

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.

Oral ingestion of Streptococcus thermophilus does not affect mucositis severity or tumor progression in the tumor-bearing rat.

Preventative or adjunctive agents for the amelioration of small intestinal chemotherapy-induced mucositis are not currently available for clinical use. We have previously demonstrated that oral ingestion of Streptococcus thermophilus (TH-4) partially attenuated chemotherapy-induced mucositis in the rat. Here we assess the effects of TH-4 on small intestinal damage and tumor progression in tumor-bearing rats with experimentally-induced mucositis. Female Dark Agouti tumor-bearing (mammary adenocarcinoma) rats (n = 36; 139 ± 1 g) had small intestinal damage induced via the administration of methotrexate (MTX). Rats were administered MTX; (1.5 mg/kg intramuscular) or saline at 0 and 24 h; with daily gavage administration of TH-4 (109 cfu/mL) or skim milk from -48 to +96 h post-MTX. Rats were allocated to groups (n=9): saline control, TH-4 control, MTX control or TH-4+MTX. The non-invasive ( 13) C-sucrose breath test (SBT) was conducted prior to tumor inoculation, pre-MTX (-24 h) and prior to sacrifice (96 h) to monitor gut function. At sacrifice small intestinal segments were excised and assessed for sucrase and myeloperoxidase activity as well as histological damage. Irrespective of TH-4 treatment, MTX-treated rats had a significant decrease in bodyweight, SBT levels, sucrase and myeloperoxidase activity, and histological damage score (p < 0.05) compared to saline and TH-4 control rats. TH-4 treatment did not result in tumor progression (p > 0.05) but failed to alleviate mucositis indices. Although TH-4, at a dose of 109 cfu/mL, yielded neither protection nor amelioration of chemotherapy-induced mucositis, progression of mammary adenocarcinoma was unaffected.

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.

Evidence supporting the use of probiotics for the prevention and treatment of chemotherapy-induced intestinal mucositis.

Although chemotherapy remains the current best practice for the treatment of neoplasia, the severity of its associated side-effects continues to impact detrimentally on the quality of life. Mucositis can affect both the oral cavity and intestine, and represents one of the most common side-effects of chemotherapy. It is characterized by ulceration, inflammation, diarrhoea, and intense abdominal pain. Despite extensive research there remains no definitive therapy for mucositis. This may be due to the multiple factors which contribute to its pathogenesis, including up-regulation of pro-inflammatory cytokines, increased apoptosis of epithelial cells, alteration of the gastrointestinal microbiota, and damage to the epithelium. Although employed increasingly in other gastrointestinal disorders, probiotics are yet to be comprehensively investigated in the treatment or prevention of chemotherapy-induced mucositis. Probiotic-based therapies have been shown to exert beneficial effects, including modulation of the microbiota and inhibition of pro-inflammatory cytokines. This review outlines the current evidence supporting the use of probiotics in intestinal mucositis, and suggests further research directions for the future.

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.