R.J.M. Brummer

Glutamine and the preservation of gut integrity

Parenteral glutamine dipeptide improves nitrogen balance in postoperative patients on total parenteral nutrition (TPM). Animal studies show that the structure and function of the gut is preserved by glutamine. It is not known if this is the case in human beings. 20 patients admitted to hospital for total parenteral nutrition were randomly allocated to receive parenteral nutrition enriched with glycyl-L-glutamine (Gln TPN), or standard parenteral nutrition (STPN). Mucosal biopsy specimens were taken from the second part of the duodenum before starting parenteral nutrition, and after two weeks. The ratio between the urine concentrations of lactulose and mannitol after enteral administration was used to measure intestinal permeability. After two weeks of parenteral nutrition in the GlnTPN group, intestinal permeability was unchanged, whereas permeability in the STPN group increased. Villus height was unaltered in the GlnTPN group but in the STPN group it decreased. The addition of glutamine to parenteral nutrition prevents deterioration of gut permeability and preserves mucosal structure.

Diet as a risk factor for the development of ulcerative colitis

OBJECTIVE:Dietary factors have been considered as a possible risk factor for ulcerative colitis (UC). However, available data are inconsistent. The aim of the present study was to evaluate the etiological role of dietary factors in the development of UC.METHODS:Recently diagnosed (<6 Months) UC patients (n = 43) and age- and gender-matched population controls (n = 43) were studied in a case-control design. The cross-check dietary history method was used to assess dietary intake of 5 yr before the study. Adipose tissue fatty acid composition was used as a biomarker of long-term fat intake. Conditional logistic regression-derived odds ratios (OR), and 95% confidence intervals (CI) were used for statistical analysis. Dietary intake ORs were adjusted for energy intake.RESULTS:High intakes of monounsaturated fat (OR: 33.9 [95% CI 2.6–443.1]), polyunsaturated fat (OR: 5.1 [95% CI 1.0–26.7]), and vitamin B6 (OR: 6.9 [95% CI 1.6–30.7]) were associated with an increased risk to develop UC. No other significant associations were found with UC risk.CONCLUSIONS:High intakes of mono- and polyunsaturated fat and vitamin B6 may enhance the risk of developing UC. Whether this observation is a true risk factor in the development of UC or rather a reflection of a certain dietary lifestyle needs to be investigated.

Gut permeability, intestinal morphology, and nutritional depletion.

Nutritional depletion increases the risk for postoperative complications. The intestinal barrier may be important in the underlying pathophysiologic mechanism. In this study, 26 patients were evaluated to determine whether nutritional depletion was related to gut integrity and intestinal morphology. Nutritional depletion was estimated by calculating percentage ideal body weight (PIB) or percentage ideal fat free mass (PIFFM). To assess gut integrity, a lactulose/mannitol (L/M) test was performed. Duodenal biopsies were taken, and villous height, crypt depth, number of IgA-producing plasma cells, intraepithelial lymphocytes (IELs), and proliferating index were determined. The L/M ratio was increased, and villous height was decreased in depleted patients. Depletion was not associated with differences in the number of immune cells or proliferating index. The number of IgA-producing plasma cells was positively correlated with the L/M ratio. This study shows that nutritional depletion is associated with increased intestinal permeability and a decrease in villous height.

Acute tryptophan depletion affects brain-gut responses in irritable bowel syndrome patients and controls

Background: Serotonin, a key denominator of the brain-gut axis, is involved in the regulation of gastrointestinal motility, secretion, and perception as well as cognition and mood. Aim: To assess the effects of an acutely lowered serotonin synthesis, using the acute tryptophan depletion (ATD) method, on visceral perception, affective memory performance, and mood in diarrhoea predominant irritable bowel syndrome patients (d-IBS) and controls. Methods: In a randomised, double blind, crossover design, 14 d-IBS patients and fourteen matched controls were studied under ATD and placebo conditions, respectively. Perception of urge and pain was scored during rectal distensions. Affective memory performance, mood, and biochemical parameters of serotonergic metabolism were simultaneously assessed. Results: ATD significantly decreased plasma tryptophan (67.0 (2.0) v 24.9 (2.0) μmol/l) and 5-hydroxyindole acetic acid concentrations (29.9 (1.0) v 15.8 (0.6) nmol/l). ATD was associated with significantly increased urge scores specifically in the lower pressure range and overall increased pain scores. ATD significantly lowered the perceptual threshold for first perception compared with placebo (patients 10.6 (1.2) v 13.6 (0.8) mm Hg, controls 12.6 (1.3) v 15.7 (1.2) mm Hg) but not for maximal tolerable discomfort (patients 50.5 (3.6) v 51.6 (3.3) mm Hg, controls 50.9 (3.3) v 48.8 (2.9) mm Hg). ATD induced a significant shift in affective memory bias towards preferential loss of positive material but no significant changes in mood. ATD did not differentially affect the patient or control group. Conclusions: We have provided evidence that serotonergic modulation by ATD affects both visceral perception as well as cognition in d-IBS and controls. Simultaneous measurement of brain and gut function and the application of ATD contribute to the elucidation of the complex pathophysiology of IBS.

Fat intake and fatty acid profile in plasma phospholipids and adipose tissue in patients with Crohn's disease, compared with controls.

Objectives:Fatty acid metabolism is involved in the immune response and inflammation processes in patients with Crohns disease (CD). Fatty acid changes may be relevant to the clinical course of the disease. The aim of this study was to compare the qualitative and quantitative fat intake and fatty acid composition of plasma phospholipids and adipose tissue in a defined population of CD patients with those in matched controls.Methods:Dietary fat intake and fatty acid profile of plasma phospholipids and adipose tissue were assessed in two patient populations: 20 patients with recently diagnosed CD and 32 patients with longstanding (>10 yr) CD clinically in remission, matched for age and gender with healthy controls.Results:We observed no significant differences in quantitative or qualitative fat intake between CD patients and controls. Percentages of linoleic acid and α-linolenic acid in plasma phospholipids or adipose tissue were not significantly different between patients and controls. However, we observed a significantly (p < 0.05) lower percentage of the sum of the n-3 fatty acids, with significantly (p < 0.01) higher levels of clupanodonic acid (22:5n-3) and significantly (p < 0.05) lower levels of docosahexaenoic (22:6n-3) and arachidonic acid (20:4n-6). The aberrant fatty acid profile was more evident in patients with longstanding CD than in patients with recently diagnosed CD.Conclusion:The aberrant fatty acid profile found in these CD patients is a result of altered metabolism rather than of essential fatty acid malabsorption. The reported findings may be important in the pathophysiology of CD and hence in the choice of fatty acids to be used when therapeutic supplementation is considered in CD patients.

Effect of dehydration on gastrointestinal function at rest and during exercise in humans

Abstract Dehydration leads to the aggravation of gastrointestinal (GI) complaints during exercise. The aim of this study was to examine the effect of dehydration on various GI parameters during strenuous exercise. Ten healthy well-trained men were investigated in dehydrated and in euhydrated conditions. Dehydration took place before the experiments using a dehydration regimen in a sauna leading to a 3% loss of body mass. Each experiment consisted of 1 h pre-exercise rest, 1.5 h cycling at 70% maximal exercise intensity, and 3.5 h post-exercise rest. During cycling, liquid gastric emptying (GE), orocaecal transit time (OCTT) and intestinal permeability and glucose absorption were measured. The GI-symptoms were scored using a questionnaire. Body temperature, plasma volume and vasopressin were measured before and after cycling. The GE was significantly slower during dehydration [median time to peak 13C enrichment in the breath sample (13C-TTP) 23.6 min, range 13.7–50.0 min, P=0.02] than in the control situation (median 13C-TTP 17.1 min, range 9.8–38.4 min). The OCTT was unchanged (median 173 min, range 98–263 min compared to median 128 min, range 98–195 min, P=0.18). Dehydration did not change intestinal permeability, glucose absorption, plasma volume, rectal temperature or plasma vasopressin concentration. In the dehydration experiment, exercise induced a significant increase in nausea (P=0.01) and epigastric cramps (P=0.05), in contrast to the control situation. In both experiments, exercise led to a significant increase in rectal temperature and plasma vasopressin concentration, and a significant decrease in plasma volume. The increase in plasma vasopressin concentration was significantly higher in the dehydration experiment (P=0.015). No significant differences in either the post-exercise rectal temperatures or in plasma volumes was observed. The difference in GE between the two experiments was significantly correlated with the difference in nausea score (r=0.87, P=0.002). We concluded that dehydration leads to a delayed GE but not to differences in OCTT, intestinal permeability or glucose uptake during intense cycling. The delay in GE is significantly associated with an increase in exercise-induced nausea.

Serotonergic modulators in the treatment of irritable bowel syndrome — influence on psychiatric and gastrointestinal symptoms

Background : Both central and peripheral serotonergic modulators are used in the treatment of irritable bowel syndrome. The majority of patients with irritable bowel syndrome presenting to a gastroenterologist demonstrate affective dysregulation. Serotonin may play a regulatory role in both gastrointestinal motility and sensitivity, as well as in affective dysregulation, in irritable bowel syndrome.

Performance of the [13C]-acetate gastric emptying breath test during physical exercise

The gastric emptying rate of liquids can be determined non‐invasively using the [13C]‐acetate breath test at rest. The aims of our study were to validate this test during physical exercise against the double‐sampling method and to evaluate the time needed for intestinal absorption and the delay between absorption and appearance of 13CO2 in breath, both at rest and during exercise.

Effects of pre- and post-absorptive factors on the lactulose/rhamnose gut permeability test

It is assumed that the outcome of the lactulose/rhamnose gut permeability test is not influenced by pre- or post-absorptive factors. The aim of our study was to investigate the role of a pre-absorptive factor, i.e. small-intestinal transit, and a post-absorptive factor, i.e. renal clearance. Ten healthy male subjects were studied. Urinary lactulose and rhamnose excretion was measured after intraduodenal administration of lactulose and rhamnose following induction of increased intestinal permeability using chenodeoxycholic acid (chenodiol), in the absence and in the presence of accelerated intestinal transit. Urinary sugar excretion was measured after intravenous administration of either a regular dose (50 mg/50 mg) or a high dose (250 mg/250 mg) of lactulose/rhamnose. The intraduodenal experiments showed that a combination of accelerated small-bowel transit and increased permeability did not lead to significant differences in the recovery of lactulose (P=0.647) or rhamnose (P=0.889), or in the lactulose/rhamnose ratio, compared with those under conditions of increased permeability alone (P=0.68). However, lactulose recovery was significantly lower (P=0.025) after intravenous administration of a high dose of the sugars. There was no significant difference in urinary rhamnose recovery (P=0.575) between the high and the regular doses. This resulted in a significantly lower lactulose/rhamnose ratio (P=0.021) after intravenous administration of a high dose, compared with a regular dose, of the sugars. In conclusion, the assumption that post-absorptive processes do not influence the outcome of the lactulose/rhamnose permeability test appears not to be valid.

The sensitivity of the lactulose/rhamnose gut permeability test

BACKGROUND The lactulose/rhamnose (L/R) intestinal permeability test is widely used. However, different quantities and proportions of lactulose and rhamnose are used. The aim of this study was to determine whether a low dosage of lactulose is able to discriminate between normal and increased permeability. MATERIALS AND METHODS Two groups of 10 healthy subjects were studied. In group 1, three different iso-osmolar test solutions were administered on 3 days. The solutions consisted of 10 g of L with 1 g of R, 5 g of L with 0.5 g of R and 1 g of L with 0.1 g of R in 65 mL of water. Group 2 ingested these solutions 1 h after ingestion of 750 mg of chenodeoxycholeic acid (CDCA), which is known to increase permeability. The urinary L/R ratio was determined using high-performance liquid chromatography. Data are presented as medians (range). RESULTS In group 1, no differences were observed between the three solutions. In Group 2, there was a significant difference (P = 0.045) between the three solutions. The L/R ratios were 0.0079 (0.0024-0.0152) (1L to 0.1R), 0.0138 (0.0066-0.0192) (5L to 0.5R) and 0.0144 (0.0074-0.0374) (10L to 1R). The L/R ratio differed significantly between Groups 1 and 2 (P < 0.001) using the 5L to 0.5R and 10L to 1R solutions respectively. CONCLUSION If the permeability is increased, the urinary L/R ratio depends on the quantity of lactulose and rhamnose administered in equal proportion. 5L to 0.5R is sufficient to discriminate between a normal and a moderately increased permeability.