Sucrose Breath Test Research Articles

Optimising the carbon 13 sucrose breath test for the assessment of environmental enteric dysfunction

Optimising the carbon 13 sucrose breath test for the assessment of environmental enteric dysfunction

Labelled Carbon Sucrose Breath Test (13C-SBT) as a Marker of Environmental Enteropathy

Labelled Carbon Sucrose Breath Test (13C-SBT) as a Marker of Environmental Enteropathy

Combined Effects of Muricid Extract and 5-Fluorouracil on Intestinal Toxicity in Rats.

Chemotherapy drugs, such as 5-fluorouracil (5FU), are the standard approach for cancer and are associated with several peripheral toxicities. We previously demonstrated that Muricidae marine molluscs exhibit chemopreventive properties. This study investigated the combined effect of muricid extract derived from Dicathais orbita, with 5FU, on intestinal toxicity in rats. Groups of rats were orally gavaged water, muricid extract, or sunflower oil, with or without 5FU (150 mg/kg). Metabolic data was collected daily and small intestinal brush border enzyme activity was measured by sucrose breath test (SBT). Blood was collected by cardiac puncture for whole blood analysis. Intestinal biopsies were taken for histopathology. Neutrophil activity was measured by myeloperoxidase activity. No additional toxicity effects were observed in rats receiving the combination of 5FU and muricid extract compared to 5FU alone, as indicated by SBT, histopathology, and myeloperoxidase activity. Intestinal integrity was protected from 5FU-induced damage in the sunflower oil vehicle group, compared to controls, as measured by SBT, villus height, and crypt depth. We concluded that combination of muricid extract and 5FU did not confer any additional intestinal toxicity, further supporting its potential as a chemopreventive food product. In this model system, sunflower oil partially protected against 5FU-induced intestinal toxicity.

Grape Seed Extract Reduces the Severity of Selected Disease Markers in the Proximal Colon of Dextran Sulphate Sodium-Induced Colitis in Rats

Grape seed extract (GSE) constitutes a rich source of procyanidins. GSE has been demonstrated to exert encouraging anti-inflammatory and anti-ulcer properties in experimental settings, although its effects on inflammation of the colon remain undefined. To determine the effects of GSE in a rat model of dextran sulphate sodium (DSS) for ulcerative colitis. Male Sprague-Dawley rats were gavaged daily (days 0-10) with GSE (400 mg/kg). Ulcerative colitis was induced by substituting DSS (2 % w/v) for drinking water from days 5-10. A sucrose breath test was performed on day 11 to determine small bowel function and intestinal tissues were collected for histological analyses. Statistical analysis was by one-way or repeated-measures ANOVA and p < 0.05 was considered significant. Compared to DSS-treated controls, GSE significantly decreased ileal villus height (14 %; p < 0.01) and mucosal thickness (13 %; p < 0.01) towards the values of normal controls. GSE reduced qualitative histological severity score (p < 0.05) in the proximal colon, although no significant effect was evident in the distal colon. However, GSE failed to prevent DSS-induced damage to the crypts of both colonic regions. Administration of GSE did not negatively impact metabolic parameters, nor did it induce any deleterious gastrointestinal side effects in healthy animals. GSE decreased the severity of selected markers of DSS-induced colitis in the distal ileum and proximal colon, suggesting the potential as an adjuvant therapy for the treatment of ulcerative colitis. Future studies of GSE should investigate alternative delivery methods and treatment regimens, further seeking to identify the individual bioactive factors.

Biomarkers of Small Intestinal Mucosal Damage Induced by Chemotherapy: An Emerging Role for the 13C Sucrose Breath Test

Gastrointestinal mucosal toxicity is extremely common following cytotoxic therapies. The alimentary mucosa is particularly susceptible to injury and dysfunction, leading to many debilitating complications. Despite much research, there is currently no single noninvasive biomarker to detect gut injury. Several biomarkers have been investigated in the context of gastrointestinal diseases, which may prove useful in the oncology arena. Identification of a biomarker that is easy to obtain and measure and that accurately identifies mucosal damage would allow for improved patient diagnosis of toxicities and for personalized treatment regimens. In this review, we highlight the effectiveness of urine and breath tests as potential clinically effective biomarkers, with significant focus placed on the emerging role of the carbon-13 sucrose breath test (13C SBT). The 13C SBT provides a simple, noninvasive, and integrated measure of gut function. The 13C SBT also has the potential to monitor gut function in the setting of cytotoxic therapy-induced mucositis, or in the assessment of the efficacy of antimucositis agents.

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.

Efficacy of Lactobacillus GG in aboriginal children with acute diarrhoeal disease: a randomised clinical trial.

The effectiveness of probiotic therapy for acute rotavirus infectious diarrhoea in an indigenous setting with bacterial/parasitic diarrhoea is unclear. In the present study, we assessed the efficacy of probiotics in Australian Aboriginal children in the Northern Territory admitted to hospital with diarrhoeal disease. A randomised double-blind placebo-controlled study was conducted in Aboriginal children (ages 4 months-2 years), admitted to hospital with acute diarrhoeal disease (>3 loose stools per day). Children received either oral Lactobacillus GG (5 x 10(9) colony-forming units 3 times per day for 3 days; n = 33) or placebo (n = 31). Small intestinal functional capacity was assessed by the noninvasive 13C-sucrose breath test on days 1 and 4. Both groups showed mean improvement in the sucrose breath test after 4 days; however, there was no difference (mean, 95% confidence interval) between probiotic (2.9 [cumulative percentage of dose recovered at 90 minutes]; 1.7-4.2) and placebo (3.7; 2.3-5.2) groups. Probiotics did not change the duration of diarrhoea, total diarrhoea stools, or diarrhoea score compared with placebo. There was a significant (P < 0.05) difference in diarrhoea frequency on day 2 between probiotics (3.3 [loose stools]; 2.5-4.3) and placebo (4.7; 3.8-5.7) groups. Lactobacillus GG did not appear to enhance short-term recovery following acute diarrhoeal illness in this setting.

Orally administered emu oil decreases acute inflammation and alters selected small intestinal parameters in a rat model of mucositis

Mucositis resulting from cancer chemotherapy is a serious disorder of the alimentary tract. Emu oil has demonstrated anti-inflammatory properties in animal models of arthritis and wound healing; however, its effects on the intestine remain unknown. We investigated emu oil for its potential to decrease the severity of mucositis in a rat model. Female Dark Agouti rats (110-150 g) were orogastrically gavaged with emu oil (0.5 or 1 ml) or water (1 ml) for 5 d before intraperitoneal injection of 5-fluorouracil (5-FU, 150 mg/kg) or saline (control), and this was continued up to the day of sacrifice (48, 72 and 96 h post 5-FU administration). Histological (villus height, crypt depth (CD) and disease severity score) and biochemical (myeloperoxidase (MPO) activity) parameters were determined in intestinal tissues collected at sacrifice. Sucrase activity in vivo was quantified by the sucrose breath test. Activated neutrophil activity (MPO) in the ileum was significantly decreased by emu oil (0.5 ml, 451 (sem 168) U/g and 1 ml, 503 (sem 213) U/g) compared with 5-FU-treated controls (1724 (sem 431) U/g) 96 h post 5-FU administration. There were also significant increases in CD (152 (sem 8) microm) in the ileum of rats that received 1 ml emu oil at 96 h compared with 5-FU-treated controls (CD (106 (sem 12) microm)). Emu oil did not affect sucrase activity. Emu oil decreased acute ileal inflammation, and improved mucosal architecture in the intestine during recovery from chemotherapy in rats. Further studies investigating the potential benefits of emu oil as a nutritional supplement for the treatment of intestinal disorders are indicated.

Use of the sucrose breath test to assess methotrexate‐induced mucositis following zinc supplementation

This study investigated the efficacy of zinc (Zn) supplementation to ameliorate methotrexate (MTX)‐induced intestinal mucositis in mice. MT‐I&amp;‐II null (MT−/−) and wild‐type (MT+/+) mice were fed either a 10 (control) or 400 mg Zn/kg diet (high Zn) for 7 days at which time intestinal mucositis was induced by a single subcutaneous injection of MTX (500 mg/kg). Mice were sacrificed at 24 and 72 h post MTX injection while continuing their respective diets. The sucrose breath test (SBT) was used to assess small intestinal integrity and was performed prior to feeding the Zn diets, 5 days after and 24 and 72 h post MTX injection. MT+/+ mice (4.5 (1–8); median (ranges)) had significantly (p&lt;0.05) lower histological severity scores compared to MT−/− mice (8.8 (4–13)), irrespective of Zn intake. Small bowel MTX‐induced damage, as assessed by the SBT, was significantly (p&lt;0.05) decreased in MT+/+ (16.1 ± 1.2 cumulative % dose recovered at 90 min; mean±SEM) compared to MT−/− mice (12.4 ± 1.2), irrespective of time and diet. This was most prominent at 72 h post MTX administration (MT+/+; 11.9 ± 2.0 vs MT−/−; 7.3 ± 2.5). Dietary Zn did not ameliorate MTX‐induced gut damage in either MT+/+ or MT−/− mice as assessed by the SBT or histologically. Zn supplementation did not ameliorate MTX‐induced gut damage. The presence of MT was protective against small intestinal damaged induced by MTX, assessed by the SBT.

Measuring tools for gastrointestinal toxicity

The present review is timely owing to the previous paucity of biomarkers, particularly functional noninvasive tests, to evaluate the extent and severity of gastrointestinal toxicity in both animal models of chemotherapy and in cancer patients undergoing chemotherapy. The most recent findings using noninvasive functional biomarkers now allow longitudinal monitoring of the time course of damage and repair that occurs in the gastrointestinal tract following radiotherapy and chemotherapy. This monitoring has in turn enabled collection of objective evidence for efficacy of new antimucositis agents using animal models and, more importantly, for use in future randomized, double-blind, placebo-controlled clinical trials. In the past 12 months the C sucrose breath test has been applied to a series of animal models of chemotherapeutic damage, showing rapid monitoring of the efficacy of particular bioactive molecules is now possible at different stages of the damage and repair cycle. This biomarker has also been applied to childhood cancer studies of mucositis and now needs to be used in adult cancers for eventual adoption in routine clinical management of mucositis. An exciting possibility would be extension of the biomarker use to predict damage in other regions of the gastrointestinal tract, including oral mucosa.

1133 POSTER Residual damage to the small intestine induced by chemotherapy can be detected and monitored using the non-invasive 13C Sucrose Breath Test (SBT)

1133 POSTER Residual damage to the small intestine induced by chemotherapy can be detected and monitored using the non-invasive 13C Sucrose Breath Test (SBT)

Probiotic Effects on 5-Fluorouracil-Induced Mucositis Assessed by the Sucrose Breath Test in Rats

The sucrose breath test (SBT) was employed to noninvasively assess the efficacy of probiotics in 5-fluorouracil (5-FU)-induced intestinal mucositis. Dark Agouti rats were allocated to 5 groups (n = 10): 5-FU + L. fermentum BR 11, 5-FU + L. rhamnosus GG, 5-FU + B. lactis BB 12, 5-FU + skim milk (SM), and saline + SM. Probiotics were administered by oral gavage for 10 days. Mucositis was induced on day 7 by intraperitoneal injection of 5-FU (150 mg/kg) or vehicle (saline). Rats were sacrificed 72 h after 5-FU injection. The SBT measured breath 13CO2 (expressed as percentage cumulative dose at 90 min; %CD90) on days 0, 7, and 10. %CD90 was significantly lower in 5-FU-treated controls compared with that in saline-treated controls on day 10. 5-FU caused an 83% reduction in sucrase and a 510% increase in MPO activity. The SBT detected damage induced by 5-FU and is a simple, noninvasive indicator of small bowel injury. The probiotics assessed offered no protection from mucositis at the dose tested.

A non-invasive method for detection of intestinal mucositis induced by different classes of chemotherapy drugs in the rat

Background: The Sucrose Breath Test (SBT) is a simple non-invasive technique for the detection of small intestinal mucositis. Aim: We utilised rat models of intestinal mucositis induced by different classes of chemotherapeutic agents to broaden application of the SBT. Methods: Mucositis was induced in rats by injection of Doxorubicin (Dox), Etoposide (Etop), Irinotecan (Irin), or Cyclophosphamide (Cy) and Etop in combination (Cy+Etop). The SBT was carried out following sucrose gavage, 72h after chemotherapy. At kill, intestinal tissues were collected for mucositis assessments. Results: SBT for controls was 16.0 ± 0.6% (mean ± SEM) cumulative dose at 90 min. Irin, Doxo, Etop, and Cy+Etop significantly decreased the SBT to 53%, 43%, 32% and 30% of saline control values, respectively (p<0.01) whilst sucrase activity was correspondingly decreased to 60%, 36%, 14% and 2%. There was good concordance with histological mucositis severity in the jejunum, with median scores of 11, 19, 28 and 27. Correlations between SBT, sucrase activity, and histological severity score yielded r2 values of 0.82. Conclusions: The SBT detected mucositis induced by the alkylating agent, anthracycline and DNA-topoisomerase inhibitor classes, facilitating the detection of small intestinal dysfunction, providing a further means to screen newly-developed drugs for intestinal side-effects.

Use of the 13C-sucrose breath test to assess chemotherapy-induced small intestinal mucositis in the rat

Mucositis is a debilitating side-effect of chemotherapy which affects the mucosa of the gastrointestinal tract, particularly the small intestine. Currently there are no simple, non-invasive methods to detect and monitor small intestinal function and the severity of mucosal damage. Activity of the brush-border enzyme sucrase provides an indicator of small intestinal absorptive function that remains relatively constant throughout life. Measuring 13CO-2 levels in expired breath following ingestion of 13C-sucrose is a non-invasive marker of total intestinal sucrase activity. We evaluated the sucrose breath test (SBT) as an indicator of small intestinal injury and dysfunction, utilizing a rat model of chemotherapy-induced mucositis. SBT results reflected the time-course of damage and repair after methotrexate (MTX) treatment, with damage most severe 72 h after chemotherapy, and repair commencing after 96 h. SBT results correlated significantly with jejunal sucrase activity determined biochemically (r2=0.89; p

101 INTESTINAL INFLAMMATION IN VIPOMA — ASSOCIATED DIARRHEA.

VIPoma secreting tumors are a rare cause of chronic diarrhea in children. Previous reports have demonstrated normal small intestinal mucosal architecture. We present two children with chronic diarrhea in whom abnormal gastrointestinal mucosal biopsies were found and delayed an eventual diagnosis of VIP secretory tumors. Case 1: An 18 month old male was referred with a 2 month history of 10 watery stools/day. Mild hypokalemia and acidemia were detected. Gastrointestinal mucosal biopsies revealed a patchy villous injury in the duodenum, mild active duodenitis, mild esophagitis, and a focal colitis. Because of persistent symptoms on an elemental diet a VIP level was obtained and was elevated at 310 pg/ml (NI < 70 pg/mL). CT scan revealed a right adrenal mass which was found do be a ganglioneuroblastoma. Case 2: An 11 month old girl presented with a 6 week history of watery diarrhea. Stool was negative for enteropathogens but positive for Clostridium difficile toxin. Antigliadin and antiendomysial antibodies were negative. A sucrose breath test was normal. Electrolytes showed hypokalemia and acidemia. An abdominal ultrasound was reported as normal. She continued to have watery stools. Endoscopy revealed chronic duodenitis with increased eosinophils, mild antritis, and moderate chronic active esophagitis. Rectal biopsy showed mild superficial proctitis with increased eosinophils. No improvement was seen on a milk and soy-free diet. A VIP level came back at 430 pg/mL. An abdominal CT revealed a left adrenal tumor which was found to be a ganglioneuroma. Immunostaining for VIP was strongly reactive. After surgery the diarrhea resolved completely in both patients. Conclusions: Gastrointestinal mucosal inflammation mimicking mild allergic enterocolitis may be found in children with VIPoma associated diarrhea. The cause of gastrointestinal inflammation in these patients is not known. Possible explanations include a concomitant allergic enteropathy or effect of proinflammatory substances secreted by the tumor (e.g. Substance P). Clinicians should note that the presence of gastrointestinal inflammation does not exclude the diagnosis of functioning neural crest tumors in children.

Modification of Metrazol‐induced convulsions by ablations of the brain

<h3>Purpose</h3> Children with type 1 diabetes mellitus (T1DM) have an increased risk for celiac disease (CD), despite absence of clinical symptoms of CD. Benefits of screening and early treatment of CD are unknown. Our objective is to evaluate the impact of early treatment of CD on the growth, intestinal permeability, diabetes control, and bone density of subjects with diabetes and celiac autoimmunity (tissue tranglutaminase antibody (TG) positivity). <h3>Methods</h3> This is a prospective, observational study of children with T1DM characterized as TG+ or TG- through screening. TG+ subjects self-select to gluten-free diet (GFD) or regular diet (RD). Primary outcomes are diabetes control, intestinal permeability, growth, and bone density. Data are mean ± SD. <h3>Results</h3> To date, 42 TG+ subjects have completed the baseline visit (22 GFD, 20 RD), 30 have completed the 6 month visit (17 GFD, 13 RD), and 21 have completed the 12 month visit (10 GFD, 11 RD). At baseline there are no significant differences between the TG+ groups (mean age for GFD group was 10.2 ± 3.3 years, and RD group was 11.4 ± 3.4; duration of diabetes was 5.4 ± 3.9 years for GFD group and 7.2 ± 3.4 for RD group; mean duration of GFD was 10.4 ± 1.0 months; TG index was 0.63 ± .56 in GFD group and 0.4 ± 0.38 in RD group; HbA1C was 8.15% ± 1.2 for GFD group and 8.9% ±1.5 for RD group; and the height z-score was -0.24 ± 1.18 for GFD group, and 0.07 ± 1.1 for RD group). There were also no significant differences between the TG+ groups at 6 or 12 months for any variables including race, gender, ethnicity, age, diabetes duration, TG index, HbA1C, urine microalbumin, and z-scores for body mass index, height-for-age, and weight-for-age. Additionally, there were no differences for lumbar or volumetric spine z-scores for chronological or bone age, nor differences in intestinal permeability as measured by sucrose breath test between groups at baseline or 12 months. Report of symptoms also did not differ at baseline or 12 months, but an increase in flatulence was reported in the RD group at 6 months. <h3>Conclusions</h3> There were no significant differences between the TG+ groups at baseline, 6 months, or 12 months. Therefore, there is no evidence of benefit of GFD at one year. Further enrollment and follow-up is needed to determine whether there are benefits to screening for CD in children with T1DM and whether early initiation of GFD is necessary in patients with CD.