Short chain fatty acids in human gut and metabolic health.

Evidence is accumulating that short chain fatty acids (SCFA) play an important role in the maintenance of gut and metabolic health. The SCFA acetate, propionate and butyrate are produced from the microbial fermentation of indigestible carbohydrates and appear to be key mediators of the beneficial effects elicited by the gut microbiome. Microbial SCFA production is essential for gut integrity by regulating the luminal pH, mucus production, providing fuel for epithelial cells and effects on mucosal immune function. SCFA also directly modulate host metabolic health through a range of tissue-specific mechanisms related to appetite regulation, energy expenditure, glucose homeostasis and immunomodulation. Therefore, an increased microbial SCFA production can be considered as a health benefit, but data are mainly based on animal studies, whereas well-controlled human studies are limited. In this review an expert group by ILSI Europe's Prebiotics Task Force discussed the current scientific knowledge on SCFA to consider the relationship between SCFA and gut and metabolic health with a particular focus on human evidence. Overall, the available mechanistic data and limited human data on the metabolic consequences of elevated gut-derived SCFA production strongly suggest that increasing SCFA production could be a valuable strategy in the preventing gastro-intestinal dysfunction, obesity and type 2 diabetes mellitus. Nevertheless, there is an urgent need for well controlled longer term human SCFA intervention studies, including measurement of SCFA fluxes and kinetics, the heterogeneity in response based on metabolic phenotype, the type of dietary fibre and fermentation site in fibre intervention studies and the control for factors that could shape the microbiome like diet, physical activity and use of medication.

The effect of arabinoxylooligosaccharides on upper gastroduodenal motility and hunger ratings in humans.

BACKGROUND AND AIMS: Prebiotics such as Arabinoxylooligosaccharides (AXOS) are non-digestible, fermentable food ingredients stimulating growth/activity of colonic bacteria with enhanced carbohydrates fermentation (CF) in humans. The migrating motor complex (MMC) of the gastrointestinal tract has been recently identified as an important hunger signal, but no data are available yet on the role of acute CF on MMC activity and related hunger ratings. Thus, we aimed to study the effect of acute AXOS CF on MMC and hunger in humans. METHODS: A total of 13 healthy volunteers were randomized in a single-blind crossover placebo-controlled study where 9.4 g of AXOS or 10 g of maltodextrin and 1 g of unlabelled lactose ureide (LU) were given 12 hours prior to the study and, in the next morning, together with a pancake containing 500 mg of 13 C-LU. In 10 hours after the meal, 13 CO2 and hydrogen excretion were determined every 15 minutes while hunger/appetite ratings every 2 minutes through a VAS questionnaire. Five hours after the meal, antroduodenal motility was measured using HRM. KEY RESULTS: AXOS significantly increased CF (158 ± 81 vs 840 ± 464 H2 ppm*minute, placebo vs AXOS, P < .05) without affecting the orocecal transit time (OCTT). AXOS had no significant effect on the occurrence, origin, and duration of phase III and on the total number, origin, and duration of phases I and II. Hunger and appetite scores prior and after phase III were not affected by AXOS. CONCLUSIONS: AXOS acutely increases colonic fermentation, but this neither affects OCTT, activity of the MMC, nor interdigestive hunger scores in man.

The effect of arabinoxylooligosaccharides on gastric sensory-motor function and nutrient tolerance in man.

BACKGROUND: Intestinal microbiota regulates gastrointestinal sensory-motor function. Prebiotics such as arabinoxylan-oligosaccharide (AXOS) are non-digestible, fermentable food ingredients beneficially affecting intestinal microbiota, colon activity, and improving human health. We wanted to investigate whether acute AXOS or maltodextrin (placebo) administration may alter gastric sensitivity (GS), accommodation (GA), nutrient tolerance (NT) in man. METHODS: Thirteen HV (6 M, 32.2 ± 1.8 years; BMI 22.3 ± 0.2) underwent two 48 h treatment periods with oral 4 × 9.4 g AXOS or 4 × 10 g maltodextrin (at least 1 week wash-out) for gastric barostat assessment of GS, gastric compliance (GC), GA to a liquid test meal, on day 1, and NT drink test, on day 2. Oro-cecal transit-time (OCTT), colonic fermentation (CF) were assessed simultaneously with (13) C-lactose ureide, H2 breath tests. KEY RESULTS: Arabinoxylan-oligosaccharide significantly increased CF on day 1 and 2 (565 ± 272 vs 100 ± 24, 365 ± 66 vs 281 ± 25 H2 ppm/min, AXOS vs maltodextrin, both p < 0.05), not the OCTT. AXOS did not alter GC, sensitivity before and after the meal. Gastric accommodation was not significantly influenced by AXOS (volume increment: 171 ± 33 vs 130 ± 28 mL, AXOS vs maltodextrin, p = NS). On day 1, AXOS fermentation was associated with significantly higher postprandial bloating scores (960 ± 235 vs 396 ± 138 mm*min, AXOS vs maltodextrin, p < 0.05). On day 2, AXOS did not affect maximal NT (946 ± 102 vs 894 ± 97 mL, AXOS vs maltodextrin, p = NS), increased the bloating score (1236 ± 339 vs 675 ± 197 mm*min, AXOS vs maltodextrin, p < 0.05). CONCLUSIONS & INFERENCES: Acute AXOS administration, associated with increased CF, does not affect GA, is not associated with increased meal-induced satiety or perception scores.

Postprandial symptoms originating from the stomach in functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is characterized by chronic epigastric symptoms. The stomach has been held responsible for the generation of symptoms, but the latest reports have pointed out that also the duodenum can be implicated in the pathophysiology. The aim of this study was to elucidate which dyspeptic symptoms originate from the stomach and/or from the small intestine after a meal. METHODS: Two hundred eighty-four FD patients underwent a gastric emptying breath test. Breath samples were taken and the intensity of six dyspeptic symptoms (fullness, bloating, belching, nausea, epigastric burning, and epigastric pain) was scored before a meal and at 15 min intervals for a period of 240 min postprandially. Time curves of each symptom were analyzed and severity scores during the gastric and the intestinal phase were compared. KEY RESULTS: Time curves of fullness, bloating, belching, and nausea displayed a significant negative slope, while symptom severity of epigastric burning and epigastric pain did not decrease over time. Numerical analysis revealed that scores for fullness, bloating, and belching were higher during the gastric phase compared with the intestinal phase. On the other hand, intensities of nausea, epigastric burning, and epigastric pain were similar during both phases. CONCLUSIONS & INFERENCES: Intensities of fullness, bloating, and belching decrease with food moving from the stomach to the small intestine indicating that the stomach plays a crucial role in the generation of these symptoms. In contrast, the symptom severity of epigastric burning and epigastric pain persists with progression of food to the small intestine.

In vivo CYP3A4 activity, CYP3A5 genotype, and hematocrit predict tacrolimus dose requirements and clearance in renal transplant patients.

Tacrolimus is metabolized by CYP3A4 and CYP3A5 and is characterized by a narrow therapeutic index and highly variable pharmacokinetics. This cross-sectional study in 59 renal transplant patients investigated the relationship among in vivo CYP3A4 activity (assessed using midazolam as a drug probe), CYP3A5 genotype on the one hand, and tacrolimus pharmacokinetics on the other hand, taking into account other potential determinants of tacrolimus disposition. In vivo CYP3A4 activity and CYP3A5 genotype explain 56-59% of variability in tacrolimus dose requirements and clearance, contributing ~25 and 30%, respectively. Hematocrit explains an additional 4-14%. These data indicate that CYP3A4- and CYP3A5-mediated tacrolimus metabolisms are major determinants of tacrolimus disposition in vivo and explain a substantial part of the clinically observed high interindividual variability in tacrolimus pharmacokinetics. Furthermore, these data provide a potential basis for a comprehensive approach to predicting tacrolimus dose requirement in individual patients and hence provide a strategy to tailor immunosuppressive therapy in transplant recipients.

In vivo CYP3A activity is significantly lower in cyclosporine-treated as compared with tacrolimus-treated renal allograft recipients.

In vitro studies have identified cyclosporine and tacrolimus as CYP3A inhibitors. In the current study in renal allograft recipients, we used intravenously and orally administered midazolam as a drug probe to assess whether the study drugs at doses that are generally used in clinical practice have differential effects on in vivo hepatic and first-pass CYP3A activities. Systemic and apparent oral midazolam clearance were 24% (269 ± 73 vs. 354 ± 102 ml/min, P = 0.022) and 31% (479 ± 190 vs. 688 ± 265 ml/min, P = 0.013), respectively, lower in cyclosporine-treated patients (n = 20) than in matched tacrolimus-treated patients (n = 20). The latter displayed midazolam clearances similar to those in two larger cohorts of nonmatched tacrolimus-treated patients (n = 58 and n = 80) and to those receiving a calcineurin inhibitor-free regimen (n = 6). This implies that in vivo hepatic and first-pass CYP3A activities are significantly lower in patients receiving cyclosporine than in those receiving tacrolimus, indicating that, at the doses generally used in clinical practice, cyclosporine is the stronger of the two with respect to CYP3A inhibition. This observation has important implications in the context of drug-drug interactions in transplant recipients.

Gastric emptying and different types of reflux in adult patients with cystic fibrosis.

BACKGROUND: Increased gastro-oesophageal reflux (GER) is common in patients with cystic fibrosis (CF). Previous studies showed delayed gastric emptying (GE) and a high prevalence of bile acids in saliva suggesting duodenogastro-oesophageal reflux (DGER). AIM: To assess different types of reflux (acid, weakly acidic and bile) and their relationship with rate of GE in adult CF patients. METHODS: Gastric emptying was assessed in 33 CF patients using breath tests, reflux was monitored in 42 patients using impedance-pH-metry and 14 CF patients underwent combined impedance-pH-Bilitec monitoring. RESULTS: Delayed GE was found in 33%, increased GER (predominantly acid) in 67% and pathological DGER in 35% of the CF patients. There was a significant correlation between oesophageal bile and acid exposure (P < 0.0001, r = 0.85). Patients with increased DGER had a higher proximal extent of reflux compared to those without DGER [17 (9-35) vs. 5 (1-12), P = 0.04]. There was no correlation between GE and reflux parameters, however, in a subgroup of 10 patients studied by impedance-pH-Bilitec and GE, there was a strong correlation between GE rate and bile exposure (P = 0.005, r = 0.83). CONCLUSIONS: Delayed gastric emptying is present in 1/3 of patients with cystic fibrosis. There is a subgroup of these patients with both delayed gastric emptying and increased acidic duodenogastro-oesophageal reflux with high proximal extent and risk of aspiration. Controlled studies should be performed to evaluate the effect of prokinetics or antireflux surgery on the clinical cystic fibrosis evolution in these patients.

Kinetics of butyrate metabolism in the normal colon and in ulcerative colitis: the effects of substrate concentration and carnitine on the ß-oxidation pathway.

BACKGROUND: Butyrate, a colonic metabolite of carbohydrates, is considered as the major energy source for the colonic mucosa. An impaired butyrate metabolism has been reported in ulcerative colitis (UC), however, the cause still remains unknown. AIM: In the present study, we investigated whether higher butyrate concentrations could normalise the oxidation rate in UC. Furthermore, it was investigated whether carnitine could enhance the butyrate oxidation. METHODS: Mucosal biopsies from a total of 26 UC patients and 25 controls were incubated with (14)C-labelled Na-butyrate and the produced (14)CO(2) was measured. First, the rate of oxidative metabolism was compared at three different concentrations of Na-butyrate (0.05 mm, 1 mm and 10 mm). Then, incubations of biopsies were performed with carnitine alone or combined with ATP. RESULTS: Overall, butyrate oxidation in UC was significantly lower than that in controls. The maximum rate of butyrate oxidation was achieved in UC and control subjects from 1 mm onwards. Increasing the butyrate concentration to a level to be present in the colonic lumen, i.e. 10 mm, did not increase the rate of butyrate oxidation in UC to the rate observed in controls. Addition of carnitine alone or combined with ATP caused no effects. CONCLUSIONS: Saturation of butyrate kinetics was achieved from 1 mm in UC and control subjects. The rate of butyrate metabolism was significantly impaired in active ulcerative colitis. The addition of compounds interfering with the ß-oxidation pathway had no effect on the butyrate metabolism in UC.

Analysis of the urinary glucose-[¹5N, ¹5N]-ureide content in the study of the lactose-[¹5N, ¹5N]-ureide metabolism in healthy humans.

BACKGROUND/OBJECTIVES: Lactose-[(15)N, (15)N]-ureide is used to study the fate of the colonic urea-nitrogen metabolism. During the passage through the gastrointestinal tract, lactose ureide is hydrolysed to glucose ureide, which is absorbed to a limited extent from the small intestine and is excreted urinarily. In the present study, a procedure has been developed to quantify the urinary excretion of glucose-[(15)N, (15)N]-ureide. In addition, urine and faecal samples obtained during a dietary intervention study with the prebiotic lactulose were retrospectively analysed. SUBJECTS/METHODS: The glucose ureide and lactose ureide content was measured by GC-MS in 19 healthy volunteers. After consumption of a standard test meal containing 75 mg lactose-[(15)N, (15)N]-ureide, six healthy volunteers performed a fractionated 24 h urine collection to investigate the urinary excretion of glucose-[(15)N, (15)N]-ureide. In 13 volunteers, the effect of lactulose administration on the urinary excretion of glucose-[(15)N, (15)N]-ureide was analysed. RESULTS: The urinary excretion of glucose-[(15)N, (15)N]-ureide reached its maximum level in the 3-6 h urine collection and decreased in the 6-9 h urine. The label was still detectable in the 9-24 h urine collection. The cumulative excretion of (15)N-labelled glucose ureide after 24 h amounted 12.91%. No significant differences in glucose-[(15)N, (15)N]-ureide excretion were found in either of the urine fractions after administration of lactulose, compared with baseline. In none of the urine samples lactose-[(15)N, (15)N]-ureide was detected. CONCLUSIONS: In conclusion, the results obtained in the present study indicated that the percentage dose glucose-[(15)N, (15)N]-ureide recovered in urine is rather constant and not influenced by the presence of lactulose.

Effect of mianserin on gastric sensorimotor function and gastric emptying: a randomized, placebo-controlled, double-blind, crossover study in healthy volunteers.

BACKGROUND: Antidepressants such as mianserin can improve symptoms in some functional dyspeptic patients but their mechanism of action remains unclear. We aimed to assess the effects of mianserin on gastric sensorimotor function in man. METHODS: In this randomized, placebo-controlled, double-blind, crossover study 12 healthy subjects (six men) underwent a gastric barostat study and a gastric emptying breath test after 7 days pretreatment with placebo or mianserin (20 mg; p.o.). Graded isobaric and isovolumetric distentions were performed to determine gastric compliance and sensitivity. Subsequently, intrabag pressure was held constant and the volume increase after administration of a liquid meal (200 mL; 300 kcal) was studied. Breath was sampled before and after ingestion of a test meal and half-emptying times for solids and liquids were determined from the breath samples. Mianserin was compared to placebo using t-tests and mixed model analysis (mean ± SD). KEY RESULTS: Mianserin did not affect pressures or volumes needed to induce first perception or discomfort. During isovolumetric distensions compliance was decreased after mianserin treatment (1.8 ± 0.4 vs 2.0 ± 0.3 mmHg 100 mL(-1); P < 0.05). Premeal volumes were comparable in both treatment arms (221 ± 99 vs 220 ± 88 mL), but meal-induced relaxation during the first 30 min was significantly inhibited after mianserin treatment (F(6,40) = 2.58, P < 0.05). Mianserin did not affect either solid or liquid gastric emptying. CONCLUSIONS & INFERENCES: Mianserin does not alter gastric emptying rate or sensitivity to gastric distension, but inhibits gastric accommodation to a meal in its early phase. These observations provide no explanation for the effects of mianserin in functional dyspeptic patients.

The effects of acute citalopram dosing on gastric motor function and nutrient tolerance in healthy volunteers.

BACKGROUND: It is unclear whether endogenous serotonin release is involved in the regulation of gastric motility and food intake. AIM: To study the effect of acute administration of the selective serotonin reuptake inhibitor citalopram on gastric motor function in man. METHODS: Nineteen healthy volunteers underwent a gastric barostat, gastric emptying and/or a drinking test after dosing with either placebo or citalopram (20 mg intravenously). In the barostat protocol, a flaccid bag was introduced in the stomach and inflated at intra-abdominal pressure +2 mmHg, volume was recorded before and after administration of a liquid meal (300 kcal). Gastric emptying for solids and liquids was simultaneously assessed using the ¹4C-octanoic acid/¹³C-glycine breath test. During the drink test, volunteers drank at a rate of 15 mL/min until maximal satiation. Citalopram was compared with placebo using t-tests and mixed model analysis. RESULTS: Citalopram induced a significant preprandial gastric relaxation (volume increase of 154 ± 55 mL vs. -38 ± 33 mL after placebo dosing; P < 0.05), whereas the postprandial volume increase was significantly decreased after citalopram treatment (F12.80 = 4.78, P < 0.0001; maximum volume increase was 304 ± 40 vs. 201 ± 54 mL after placebo and citalopram treatment respectively). Citalopram enhanced solid (123 ± 17 vs. 77 ± 6 min, P < 0.05) but not liquid emptying (62 ± 6 vs. 57 ± 4 min). Satiation scores during the drink test were lower after citalopram (F19.153 = 2.02, P = 0.01; volunteers drank 998 ± 129 vs. 765 ± 79 mL after citalopram and placebo treatment respectively). CONCLUSION: The observed effects indicate a role for serotonin in the control of gastric motility and food intake.

Influence of the type of indigestible carbohydrate on plasma and urine short-chain fatty acid profiles in healthy human volunteers.

BACKGROUND/OBJECTIVES: Health effects of whole grain foods are becoming more evident. In this study, we analysed the short-chain fatty acid profiles in urine and serum derived from the colonic fermentation process of (13)C-barley meals, prepared from barley grown under (13)CO(2) atmosphere. SUBJECTS/METHODS: In a crossover study, five volunteers ingested intact barley kernels (high content of non-starch polysaccharides (NSP) and resistant starch (RS)) and barley porridge (high content of NSP only). Using a newly developed stable isotope technology, we monitored 14 and 24 h postprandially (13)C-acetate, (13)C-propionate and (13)C-butyrate in plasma and urine, respectively. The oro-cecal transit time (OCTT) of the meals was measured with the hydrogen breath test. RESULTS: The OCTT was 6 h and did not differ between the two test meals. An increase of (13)C-acetate was observed already early after ingestion of the meals (<6 h) and was attributed to early fermentation of the test meal. A rise in plasma (13)C-propionate in the fermentation phase could only be detected after the porridge and not after the kernel meal. An increase in (13)C-butyrate was only found in the fermentation phase and was higher after the barley kernels. Urine (13)C-short-chain fatty acids data were consistent with these observations. CONCLUSIONS: The difference in the profiles of (13)C-acetate, (13)C-propionate and (13)C-butyrate indicates that NSP combined with RS results in an altered fermentation profile than dietary fibre alone.

Will the 13C-octanoic acid breath test ever replace scintigraphy as the gold standard to assess gastric emptying?

The applicability of the 13C-octanoic acid breath test for the assessment of gastric emptying is discussed. In the current issue of this journal, Keller and her colleagues described the application of different mathematical models for analysis of the 13C-octanoic acid test in a very large patient population.

Relationship between symptoms and ingestion of a meal in functional dyspepsia.

BACKGROUND AND AIMS: A subset of functional dyspepsia (FD) patients report meal-related symptoms, possibly representing a pathophysiologically homogeneous subgroup. The aim of the present study was to establish the time-course of symptoms in relation to meal ingestion, and to assess the relationship between self-reported meal-related symptoms and pathophysiological mechanisms in FD. METHODS: 218 FD patients (149 women, mean (SEM) age 39 (1) years) filled out a symptom questionnaire, including meal-induced aggravation. All patients underwent a gastric emptying breath test with severity (0-4) scoring of six symptoms (pain, fullness, bloating, nausea, burning and belching) at each sampling (15 min interval for 4 h). In 129 patients, gastric sensitivity and accommodation were assessed by barostat. RESULTS: The intensity of each FD symptom was significantly increased 15 min after the meal, compared with the premeal score, and remained elevated until the end of the measurement period (all p<0.05). The time-course of individual symptoms varied, with early peaks for fullness and bloating, intermediate peaks for nausea and belching, and late peaks for pain and burning. Meal-induced aggravation was reported by 79% of patients, and in these patients postprandial fullness, which peaked early, was the most intense symptom. In patients without self-reported meal-induced aggravation, epigastric pain, which had a delayed peak, was the most intense symptom and they had a lower prevalence of gastric hypersensitivity (27.5% vs 7.7%). CONCLUSION: Meal ingestion aggravates FD symptoms in the vast majority of patients, with symptom-specific time-courses. Postprandial fullness is the most severe symptom in patients reporting aggravation by a meal, while it is pain in those not reporting meal-related symptoms.

Free p-cresol is associated with cardiovascular disease in hemodialysis patients.

Cardiovascular disease (CVD) is highly prevalent in chronic kidney disease, suggesting that molecules retained in uremia might contribute to this increased risk. We explored the relationship between p-cresol, a protein-bound uremic retention solute, and CVD by comparing the strength of this relationship relative to traditional and novel cardiovascular risk factors. Univariate Cox proportional hazard analysis showed that the free serum p-cresol concentration was significantly associated with CVD when the primary end point was the time to the first cardiovascular event. In multivariate analysis, free p-cresol was significantly associated with CVD in non-diabetics. In diabetic patients, however, a significant relationship between p-cresol and cardiovascular events could not be demonstrated despite their having significantly higher p-cresol levels. Our study shows that free p-cresol is a novel cardiovascular risk factor in non-diabetic hemodialysis patients.

Baseline microbiota activity and initial bifidobacteria counts influence responses to prebiotic dosing in healthy subjects.

BACKGROUND: Dietary intervention with prebiotics can cause changes in the colonic microbiota and their metabolic activities. AIM: To investigate whether the response to prebiotic dosing is influenced by the baseline metabolic activity of the colonic flora and bifidobacteria counts. METHODS: The 4-week effect of lactulose (10 g bid.; n = 29) and oligofructose-enriched inulin (10 g bid.; n = 19) was evaluated in healthy human volunteers. Lactose-[(15)N, (15)N]-ureide was used to study the colonic NH(3)-metabolism. Urine (48 h) and faeces (72 h) were collected and analysed for p-cresol and (15)N-content by gas chromatography-mass spectrometry and isotope ratio mass spectrometer, respectively. Faecal bifidobacteria were quantified by real-time polymerase chain reaction. RESULTS: After the 4-week prebiotic administration period, the urinary excretion of p-cresol and (15)N was significantly decreased in both groups (P < 0.05) corresponding to a significantly higher faecal excretion of (15)N (P < 0.05). The decrease in urinary (15)N and p-cresol excretion significantly correlated with baseline (15)N and p-cresol levels (P < 0.05), indicating that subjects with higher baseline levels showed a higher response to prebiotic dosing. Furthermore, a significant correlation was seen between baseline bifidobacteria counts and the effect of prebiotic intake (P < 0.05). CONCLUSION: The response to prebiotic dosing, as indicated by the fate of NH(3), p-cresol and bifidobacteria, is determined by the initial colonic conditions.

Effect of dietary intervention with different pre- and probiotics on intestinal bacterial enzyme activities.

OBJECTIVE: To investigate the influence of different pre- and probiotics on faecal beta-glucuronidase and beta-glucosidase activity, as one of the claimed beneficial effects of pre- and probiotics is the hypothesis that these substrates are able to reduce the production of toxic and carcinogenic metabolites by suppressing specific enzyme activities in the colon. SETTING: Department of Gastrointestinal Research, University Hospital Gasthuisberg, KU Leuven, Belgium. DESIGN AND SUBJECTS: The effect was evaluated in a randomized, crossover study in 53 healthy volunteers who were randomly assigned to one of five treatment groups. INTERVENTIONS: At the start and after a 4-week treatment period, the healthy volunteers collected faeces during 72 h. Lactulose and oligofructose-enriched inulin (OF-IN) were chosen as prebiotics, whereas Lactobacillus casei Shirota, Bifidobacterium breve and Saccharomyces boulardii were selected as probiotics. Two synbiotic combinations were evaluated as well. The enzyme activity was assessed spectrophotometricly. RESULTS: Lactulose and OF-IN significantly decreased beta-glucuronidase activity, whereas a tendency to a decreased beta-glucuronidase activity was observed after L. casei Shirota and B. breve intake. To the contrary, B. breve increased beta-glucosidase levels. Supplementation with the synbiotic did not appear to be more beneficial than either compound alone. No influence of S. boulardii was noted. CONCLUSIONS: Administration of lactulose, OF-IN, L. casei Shirota or B. breve resulted in a decrease of the beta-glucuronidase activity, which is considered beneficial for the host.

Clinical trial: a randomized-controlled crossover study of intrapyloric injection of botulinum toxin in gastroparesis.

BACKGROUND: Uncontrolled studies suggest benefit of intrapyloric injection of botulinum toxin (botox) for the treatment of gastroparesis, but controlled data are lacking. AIM: To perform a controlled study of botox injection in gastroparesis. METHODS: Twenty-three gastroparesis patients (five men, age 45 +/- 3, 19 idiopathic) underwent two upper endoscopies with 4-week interval, with injection of saline or botox 4 x 25 U in a randomized double-blind-controlled crossover fashion. Before the start of the study and 4 weeks after each treatment, they underwent a solid and liquid gastric emptying breath test with measurement of meal-related symptom scores, and filled out the Gastroparesis Cardinal Symptom Index. Results (mean S.E.M.) were compared using Student's t-test. RESULTS: Twelve patients received botox and 11 saline as the first injection. Significant improvement in emptying and Gastroparesis Cardinal Symptom Index was seen after initial injection of saline or botox. No further improvement occurred after the second injection (respectively, botox and saline). Pooled data for both treatment groups showed no significant difference in improvements of solid t(1/2) (3.4 +/- 7.4 vs. 16.3 +/- 8.3, N.S.) and liquid t(1/2) (8.2 +/- 13.7 vs. 22.5 +/- 7.7, N.S.), meal-related symptom scores or Gastroparesis Cardinal Symptoms Index (GCSI; 6.1 +/- 1.5 vs. 3.8 +/- 1.5, N.S.). CONCLUSION: In a cohort of predominantly idiopathic gastroparesis patients, botox is not superior to placebo in improving either symptoms or the rate of gastric emptying.

Further investigations on the role of diet-induced thermogenesis in the regulation of feed intake in chickens: comparison of adult cockerels of lines selected for high or low residual feed intake.

The main objective of this study was to investigate the role of diet-induced thermogenesis (DIT) in feed intake regulation in cockerels selected for high (R+) or low (R-) residual feed intake. The selection criterion was defined as the difference between observed feed intake and feed intake predicted by regression between feed intake and BW, BW gain, and egg mass production. Furthermore, the effect of genotype on postprandial oxidation of U-(13)C(6)-glucose, decarboxylation of 1-(13)C(1)-Leu, and key metabolites and hormones was analyzed. Thirty 24-wk-old cockerels of both lines were kept in battery cages under standard conditions on a commercial diet. Three cockerels per genotype were examined twice weekly from wk 30 through 34 in open-circuit respiratory cells. After adaptation, cockerels were feed deprived for 24 h and heat production was measured. During the subsequent 7-h refeeding period, DIT and feed intake, as well as glucose oxidation and Leu decarboxylation were assessed by using breath tests. Blood samples were collected after fasting and refeeding. Finally, 10 animals per genotype were killed to record abdominal fat weight. Body composition of 6 different chickens per genotype was determined by using dual-energy x-ray absorptiometry. During feed deprivation, the R+ cockerels had a significantly higher heat production than their R- counterparts, which was even more pronounced during refeeding. Consequently, the R+ cockerels had a significantly increased DIT and a higher feed intake than the R- cockerels. Thus, no evidence of a feedback effect of DIT on feed intake was observed. The oxidation of U-(13)C(6)-glucose was significantly higher in the R+ cockerels, confirming their higher respiratory quotient values and the augmented fat deposition in the R- chickens, as assessed by abdominal fat weight and dual-energy x-ray absorptiometry measurements. No significant genotype effect on 1-(13)C(1)-Leu decarboxylation was observed, despite increased circulating uric acid levels in the R+ chickens. Genotype did not influence plasma levels of triglycerides, free fatty acids, glucose, triiodothyronine, or thyroxine after refeeding, whereas plasma leptin levels were significantly higher in the R+ cockerels.

Rate of metabolic decarboxylation of leucine as assessed by a l[1-(13)C(1)]leucine breath test combined with indirect calorimetry of broiler chickens fed isocaloric diets with different protein:fat ratio.

Research has shown that broiler chickens reared on a low-protein diet have a more efficient protein digestion. However, information on the fate of absorbed amino acids in relation to the dietary crude protein level in poultry is sparse. Therefore, this study aimed at developing a methodology for a 1-(13)C(1)-leucine breath test combined with indirect calorimetry, and to apply this technique using broiler diets known to induce differences in protein retention. From 14 days of age onwards, broiler chickens were reared on one of two isocaloric diets with substitutions between fat and protein [low-protein (LP) vs. high-protein (HP) diet: 130.4 vs. 269 g protein/kg; and 101.8 vs. 27.9 g fat/kg]. Every 4 or 5 days, three chickens per diet were placed in the respiratory cells for 48 h. The broilers were intubated with 40 mg 1-(13)C(1)-leucine/kg body weight, followed by breath sampling for 4 h at 15-min intervals and mass spectrometric analysis of the (13)C:(12)C ratio in the samples. The CO(2) level in the respiratory cell air was monitored and excreta samples were collected. The methodology to study l[1-(13)C(1)]leucine decarboxyation in chickens using a breath test combined with indirect calorimetry was accomplished. Results of the nitrogen balance test indicated that the LP broilers had an improved dietary protein retention compared with the HP animals. Moreover, LP chickens decarboxylated a significantly lower percentage of l[1-(13)C(1)]leucine, demonstrating several 'protein- or amino acid-sparing' mechanisms in animals reared on a diet with lower protein level, both at the digestive and at the postabsorptive level.