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.

Breath methane to hydrogen ratio as a surrogate marker of intestinal dysbiosis in head and neck cancer.

Exhaled breath compounds can non-invasively detect head and neck squamous cell carcinoma (HNSCC). Here we investigated exhaled compounds related to intestinal bacterial carbohydrate fermentation. Fasting breath samples were collected into 3 litre FlexFoil PLUS bags from patients awaiting a biopsy procedure for suspected HNSCC. Samples were analysed using a Syft selected ion flow-tube mass spectrometer and a Quintron BreathTracker. Two tailed non-parametric significance testing was conducted with corrections for multiple imputations. 74 patients were diagnosed (histological) with HNSCC and 61 patients were benign (controls). The methane to hydrogen ratio was significantly different between cancer and non-cancer controls (p = 0.0440). This ratio increased with tumour stage with a significant difference between T1 and T4 tumours (p = 0.0259). Hydrogen levels were significantly higher in controls who were smokers (p = 0.0129), with no smoking dependent methane changes. There were no differences in short chain fatty acids between groups. Exhaled compounds of intestinal carbohydrate fermentation can detect HNSCC patients. These findings suggest a modified carbohydrate fermentation profile in HNSCC patients that is tumour stage and smoking status dependent.

Irinotecan-Induced Mucositis Is Associated with Goblet Cell Dysregulation and Neural Cell Damage in a Tumour Bearing DA Rat Model.

Irinotecan-induced mucositis is a major oncological problem. Goblet cells secrete mucus, protecting the intestinal mucosa, with secretion altered during mucositis. The enteric nervous system is involved in regulating gut motility and secretion. The aim of this study was to determine whether enteric neural cells and goblet cells are altered following irinotecan treatment. Tumour-bearing Dark Agouti rats were administered a single dose of 175 mg/kg of irinotecan intraperitoneally and 0.01 mg/kg atropine subcutaneously. Experimental and untreated control rats were killed at times 6, 24, 48, 72, 96 and 120 h after treatment. Jejunum and colon samples were formalin fixed. Haematoxylin and eosin staining, Alcian Blue-PAS staining, and immunohistochemistry with S-100 antibody (neural cell marker) were carried out. Statistical analyses were carried out using Kruskal-Wallis test with Dunns post test, Mann Whitney U test and nonlinear regression. Total goblet cells decreased at 72 h compared with controls in the colon (p < 0.05). The percentage of cavitated goblet cells decreased compared to all other time points at 120 h in the colon. The number of S-100 positive cells in the submucosal plexus decreased in the colon (p = 0.0046) and in the myenteric plexus of the jejunum and colon (p = 0.0058 and p = 0.0022, respectively), when comparing treated with control. Enteric ganglia in the myenteric plexus of the jejunum decreased at 24 h and 96 h. Irinotecan-induced mucositis is associated with increases in mucus secretion, and enteric neural cell change. These changes may contribute to the pathophysiology of mucositis through the dysregulation of neural signalling.

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.

Gastric emptying in children with type 1 diabetes mellitus: A pilot study.

AIM: Delayed gastric emptying (GE) has been demonstrated in adults with type 1 diabetes mellitus (T1DM). Little is known about GE in children with T1DM. Most methods to measure GE are invasive, that is, scintigraphy, or are only indirectly related to GE, that is, electrogastrography. Carbon-13 breath testing is a non-invasive, very low-risk procedure that accurately correlates with GE time. This was a pilot study to determine the feasibility of using carbon-13 breath testing to measure GE in children with T1DM and healthy controls. METHODS: Cases were recruited from children aged 7-15 years presenting to the paediatric diabetic clinic at Christchurch Hospital. Controls were peers of the cases. Children with known gastrointestinal disease were excluded. After an overnight fast, each child ate a standardised pancake labelled with carbon-13 sodium octanoate. Samples of breath were collected over a 4-h period. Samples were analysed by mass spectrometry. GE half time (GET1/2 ) and GE coefficients (GEC) were calculated by linear regression to obtain a measure of GE. RESULTS: A total of 19 cases and 15 age- and gender-matched controls underwent testing. The mean GEC in the cases was 3.19 (±0.38) and 2.90 (±0.29) in controls (P = 0.03), with an effect size = 0.86. Mean GET1/2 in the cases was 99 (52.1) min and 103 (27.5) in controls (P = 0.8), with an effect size = 0.1. CONCLUSION: The study generated results suggesting that a larger study will be worthwhile to investigate the relationship between GE and T1DM.

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.

In vitro development and validation of a non-invasive (13)C-stable isotope assay for ornithine decarboxylase.

Oesophageal cancer is a significant cause of cancer related mortality, with increasing incidence worldwide. Ornithine decarboxylase (ODC) is an enzyme involved in polyamine synthesis and cellular proliferation, and ODC expression and activity has been implicated as a prognostic marker of oesophageal cancer. This study aimed to develop and optimise an in vitro (13)C-stable isotope assay for ODC activity as a non-invasive marker of oesophageal cancer. Experiments were performed in triplicate (n = 3/group/cell line) using Caco2, HeLa, Flo-1, OE33, TE7 and OE21 cell lines (colorectal, cervical, oesophageal adenocarcinoma and oesophageal squamous carcinoma respectively). Following addition of 2mM (13)C-ornithine to cells, 10 ml gas samples were collected from the headspace every 20 min for a total of five hours. Gas samples were analysed using isotope ratio mass spectrometry to quantify (13)CO2. Assay specificity was determined using the selective ODC inhibitor, N-(4'-Pyridoxil)-Ornithine(BOC)-OMe (POB). All data is expressed as δ (13)CO2 from baseline. High ODC activity was detected by (13)C-ornithine assay in Caco2 (32.00 ± 1.12 δ (13)CO2) in contrast to HeLa cells (5.44 ± 0.14 δ (13)CO2) cells. POB inhibited activity in Caco2 cells to 12.87 ± 1.10 δ (13)CO2. Differential ODC activity was detected in all oesophageal cancer cells, and 53 h incubation of cell lines with POB reduced activity by 72%, 56%, 64% and 69% in the Flo-1, OE33, OE21 and TE7 cell lines respectively. We have shown that ODC activity can be selectively detected by a non-invasive, stable-isotope (13)C-ornithine assay. ODC activity was detected in all oesophageal cancer cell lines in vitro. Further studies are indicated to quantify ODC activity in oesophageal cancer patients.

Preliminary report of the (13)C-mixed triglyceride breath test to assess timing of pancreatic enzyme replacement therapy in children with cystic fibrosis.

BACKGROUND: Despite guidelines suggesting pancreatic enzyme replacement therapy (PERT) should be taken before or during a meal, it is currently unknown whether this has benefits over administration after a meal in individuals with cystic fibrosis (CF). METHODS: 18 children with pancreatic insufficient CF were randomised to two (13)C-mixed triglyceride ((13)C-MTG) breath tests to assess lipase activity with PERT administered 10min before and 10min after a meal. Results were expressed as percentage cumulative dose recovered (PCDR) of (13)CO2 and were compared with established values in healthy subjects. Gastric half emptying time (T½) was also assessed by a (13)C-octanoate breath test. RESULTS: There was no difference in mean PCDR of (13)CO2 between taking PERT before versus after the meal (p=0.68). Eleven subjects had a greater PCDR when PERT was taken before and 7 when PERT was taken after the meal. 6/8 subjects (75%) with a lower than normal PCDR at one time point normalised PCDR when PERT timing was changed. When PERT was taken after the meal, PCDR was higher in normal vs. fast T½ (p=0.04). CONCLUSIONS: Changing PERT timing can result in normalised lipase activity. Gastric emptying rate may influence optimal timing of PERT. Clinical Trial Registration Number - This study was undertaken prior to the registration process being a commonly required practice.

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.

Non-vascular drug eluting stents as localized controlled drug delivery platform: preclinical and clinical experience.

Stents occupy an important place in the medical field for their widespread application. They have been used in vascular as well as in non-vascular organs for various reasons. Among vascular stents, development of coronary drug eluting stents (DESs) has completely revolutionised the percutaneous coronary intervention. Similarly, attempts have been made to make use of this modality in non-vascular organs. This paper focuses on the preclinical and clinical experience with drug-eluting non-vascular stents with emphasis on drug delivery systems and regulatory requirements for their development.

Chemotherapy-induced mucositis: the role of mucin secretion and regulation, and the enteric nervous system.

Alimentary mucositis is a severe, dose-limiting, toxic side effect of cytotoxic chemotherapy and radiotherapy. Patients with mucositis often have reductions or breaks imposed on cytotoxic therapy, which may lead to reduced survival. Furthermore, there is an increased risk of infection and hospitalization, compounding the cost of treatment. There are currently limited therapeutic options for mucositis, and no effective prevention available. Mucin expression and secretion have been shown to be associated with mucositis. Furthermore, mucins exhibit protective effects on the alimentary tract through reducing mechanical and chemical stress, preventing bacterial overgrowth and penetration, and digestion of the mucosa. Additionally, a number of studies have implicated some key neurotransmitters in both mucositis and mucin secretion, suggesting that the enteric nervous system may also play a key role in the development of mucositis.

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.