Chenodeoxycholic acid stimulated fibroblast growth factor 19 response - a potential biochemical test for bile acid diarrhoea.

BACKGROUND: Bile acid diarrhoea is underdiagnosed and better diagnostic tests are needed. Fasting serum fibroblast growth factor-19 (FGF19) has insufficient diagnostic value, but this may be improved by stimulation. AIM: To explore if an impaired FGF19 response identifies primary bile acid diarrhoea. METHODS: Eight patients with primary bile acid diarrhoea and eight healthy volunteers ingested (i) a meal plus 1250 mg chenodeoxycholic acid (CDCA), (ii) 1250 mg CDCA or (iii) the meal. Blood was sampled at fasting and repeatedly after stimulation. We analysed FGF19 by enzyme-linked immunosorbent assay and bile acids including 7α-hydroxy-4-cholesten-3-one by liquid chromatography-tandem mass spectrometry. RESULTS: Stimulation with the meal plus CDCA increased median FGF19 in healthy volunteers from fasting 62 pg/mL [interquartile range (IQR): 41-138] to 99 pg/mL (IQR: 67-147; P = 0.012) after 90 min and peaked after 150 min at 313 pg/mL (IQR: 54-512). This response was impaired in primary bile acid diarrhoea patients [fasting 56 pg/mL (IQR: 42-79); 90 min: 48 pg/mL [IQR: 37-63); 150 min: 57 pg/mL (48-198)]. Receiver operating characteristics (ROCAUC ) for fasting FGF19 was 0.55 (P = 0.75) and at 90 min 0.84 (P = 0.02). The difference in FGF19 from fasting to 90 min after the meal plus CDCA separated the groups (ROCAUC 1.0; P = 0.001). 7α-hydroxy-4-cholesten-3-one was elevated in primary bile acid diarrhoea (P = 0.038) and not significantly affected by stimulation. CONCLUSIONS: The FGF19 response following chenodeoxycholic acid plus meal is impaired in primary bile acid diarrhoea. This may provide a biochemical diagnostic test.

Ulcerative colitis: ultrastructure of interstitial cells in myenteric plexus.

Interstitial cells of Cajal (ICC) are key regulatory cells in the gut. In the colon of patients with severe ulcerative colitis (UC), myenteric ICC had myoid ultrastructural features and were in close contact with nerve terminals. In all patients as opposed to controls, some ICC profiles showed degenerative changes, such as lipid droplets and irregular vacuoles. Nerve terminals often appeared swollen and empty. Glial cells, muscle cells, and fibroblast-like cells (FLC) showed no alterations. FLC enclosed macrophages (MLC), which were in close contact with naked axon terminals. The organization and cytological changes may be of pathophysiological significance in patients with UC.

Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans.

BACKGROUND: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide-stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans. METHODS: Ten healthy male volunteers (21-28 years) participated in a placebo-controlled, double-blind, cross-over study. In random order and on two separate days each volunteer ingested either 50 mg sildenafil (Viagra, Pfizer, New York, N.Y., USA) or placebo. A gamma camera technique was used to measure gastric emptying and postprandial frequency of antral contractions. RESULTS: The area under the curve of gastric retention versus time of liquid or solid radiolabelled marker was not changed by sildenafil intake, nor was the postprandial frequency of antral contractions affected by sildenafil. CONCLUSION: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers.

Effect of sustained-release isosorbide dinitrate on post-prandial gastric emptying and gastroduodenal motility in healthy humans.

Nitric oxide (NO) is an inhibitory neurotransmitter released by non-adrenergic and non-cholinergic neurons that innervate the smooth muscles of the gastrointestinal tract. We examined whether NO, derived from a sustained-release preparation of isosorbide dinitrate, influenced gastric emptying and gastroduodenal motility after a meal. Eleven healthy volunteers participated in a double-blind, placebo-controlled, cross-over study. Each subject ingested 40 mg isosorbide dinitrate orally as a sustained-release formulation or oral placebo, in random order. Gastric emptying and gastroduodenal motility were measured using scintigraphic and manometric techniques. Isosorbide dinitrate did not change the area under the curve of gastric retention versus time, and did not influence the frequency of antral contractions as assessed at 15-min intervals or the integrated duodenal motility index, as recorded over consecutive 15-min periods. A 40 mg single dose of sustained-released isosorbide dinitrate does not seem to alter gastric emptying or gastroduodenal motility after a meal.

Bile acid malabsorption in patients with chronic diarrhoea: clinical value of SeHCAT test.

BACKGROUND: Bile acid malabsorption (BAM), a cause of chronic diarrhoea, can be diagnosed by the SeHCAT test. The purpose of this study was to evaluate the usefulness of SeHCAT testing by assessing the extent of BAM and describing the clinical characteristics in a group of patients with chronic diarrhoea. Clinical outcome after treatment with cholestyramine was also evaluated. METHODS: During a 5-year period (1997-2001) the SeHCAT test was performed in 135 patients in whom a primary programme for diagnostic evaluation of chronic diarrhoea had not revealed a cause. File data from 133 patients could be evaluated. RESULTS: In 44% of patients, bile acid absorption was normal with SeHCAT retention > or = 15%. Impaired SeHCAT retention was found in 56%. All patients with ileocaecal resections had retention values < 10%. Patients with microscopic colitis presented with BAM in 39%. Only one patient with idiopathic BAM presented with steatorrhoea as opposed to 11 patients with type 1 and 3 BAM. Patients with idiopathic BAM and/or SeHCAT retention values < 5% had the best response to treatment with cholestyramine. CONCLUSIONS: The SeHCAT test is of value in evaluation of patients with chronic diarrhoea as a second-line investigation with a high diagnostic yield. The only a priori parameter to predict BAM was the existence of ileocaecal resections. The result of the SeHCAT test seems to predict the benefit of treatment with cholestyramine.

Interstitial cells of Cajal in the striated musculature of the mouse esophagus.

Interstitial cells of Cajal (ICC) are important regulatory cells in the smooth muscle coats of the digestive tract. Expression of the Kit receptor tyrosine kinase was used in this study as a marker to study their distribution and development in the striated musculature of the mouse esophagus. Sections and whole-mounts were studied by immunohistochemistry. KitW-lacZ transgenic mice, which carry the lacZ reporter gene inserted in place of the first exon of the Kit gene, were processed for Xgal histochemistry, for quantitative analysis and for ultrastructural studies. Spindle-shaped ICC were scarce in both muscle layers of the thoracic esophagus, while their number increased steeply toward the cardia in the striated portion of the intraabdominal esophagus. They did not form networks and had no relationship with intrinsic myenteric ganglia and motor end-plates. They were often close to nerve fibers immunoreactive for neuronal nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP) or neuropeptide Y (NPY), but not to fibers immunoreactive for substance P (SP), calcitonin gene related peptide (CGRP), enkephalin, or the capsaicin receptor VRI. They were present in the fetus but absent in adult ICC-deficient KitW-lacZ/KitWv mice. Interstitial cells of Cajal were identified by electron microscopy by their ultrastructure in the striated muscle of the esophagus and exhibited Xgal labeling, while fibroblasts and muscle cells were unlabeled. Interstitial cells of Cajal are scattered between striated muscle cells in the mouse esophagus. They are close to nerves with defined neurochemical coding and could possibly represent specialized esophageal spindle proprioceptors.

CD34 immunoreactivity and interstitial cells of Cajal in the human and mouse gastrointestinal tract.

Immunoreactivity for the tyrosine kinase receptor Kit (Kit-ir) is an established marker for the interstitial cells of Cajal (ICC) of the gut. Recently, the presence of CD34 immunoreactivity (CD34-ir) has been reported in Kit-ir ICC around the myenteric plexus in human small intestine. Conversely, we observed that CD34-ir labeled Kit-negative fibroblast-like cells, closely adjacent to, but distinct from, the Kit-ir ICC. The existence of cells expressing both CD34-ir and Kit-ir remains controversial. CD34-ir and Kit-ir were studied by high-resolution confocal microscopy on cryostat sections of human and murine gut as well as murine whole-mounts, using specific antibodies raised to human and murine CD34, respectively. CD34-ir labeled numerous cells in all parts of the gut, in man and in mouse. CD34-ir was consistently observed in Kit-negative cells, distinct from the closely adjacent Kit-ir ICC. Thin processes of both cell types intermingled extensively, often at the limit of resolution for light microscopy. CD34-ir was also observed in Kit-negative mesenchymal cells in the submucosa, in capillaries and in mesothelial cells. CD34-ir is not a marker for Kit-ir ICC in the human and murine gut. No CD34-ir, Kit-ir-expressing cells were encountered. Conversely, CD34-ir cells, closely adjacent to, but distinct from, Kit-ir ICC were consistently identified. The intimate relationship between these cells may offer an alternative explanation for reports of CD34 and Kit co-localization. The ontogeny and function of CD34-ir cells in the gut, as well as the origin of gastrointestinal stromal tumors, remain unclear.

Distribution and ultrastructure of interstitial cells of Cajal in the mouse colon, using antibodies to Kit and Kit(W-lacZ) mice.

The roles of the interstitial cells of Cajal in the stomach and intestine are becoming increasingly clear. Interstitial cells of Cajal in the colon are less well known, however. We studied the development and distribution of the interstitial cells of Cajal in the mouse colon, using the tyrosine kinase receptor Kit as a marker. Sections and whole mounts were studied by confocal microscopy after double immunofluorescence with specific antibodies. The ultrastructure of Kit-expressing cells was examined by electron microcopy in KitW-lacz/+ transgenic mice, which carry the lacz gene inserted in place of the first exon of the Kit gene. In the subserosa, the interstitial cells of Cajal formed a two-dimensional plexus. In the myenteric area, the interstitial cells of Cajal formed a dense plexus that gradually merged with the interstitial cells of Cajal in the outer half of the circular muscle. The inner half of the circular layer was devoid of interstitial cells of Cajal whereas in the submuscular region the interstitial cells of Cajal formed a two-dimensional plexus. Tertiary nerves with various chemical codings closely followed interstitial cell of Cajal processes. By electron microscopy, Kit-expressing cells in the outer parts of the musculature had scattered caveolae, inconspicuous basal lamina and numerous mitochondria, whereas in the submuscular region they had more pronounced myoid features. Kit-expressing cells in the mouse colon are identifiable as interstitial cells of Cajal by their ultrastructure. The interstitial cells of Cajal in the mouse colon mature postnatally. They are organized into a characteristic plexus, close to the nerves with various chemical codings.

Interstitial cells of Cajal in human gut and gastrointestinal disease.

This paper reviews the distribution of interstitial cells of Cajal (ICC) in the human gastrointestinal (GI) tract, based on ultrastructural and immunohistochemical evidence. The distribution and morphology of ICC at each level of the normal GI tracts is addressed from the perspective of their functional significance. Alterations of ICC reported in achalasia of cardia, infantile hypertrophic pyloric stenosis, chronic intestinal pseudoobstruction, Hirschsprung's disease, inflammatory bowel diseases, slow transit constipation, and some other disorders of GI motility as well as in gastrointestinal stromal tumors are reviewed, with emphasis on the place of ICC in the pathophysiology of disease.

CD34+ cells in human intestine are fibroblasts adjacent to, but distinct from, interstitial cells of Cajal.

Interstitial cells of Cajal (ICC) generate the pacemaker component of the gut and play important roles in the control of gut motility. The tyrosine kinase receptor Kit is an established marker for ICC. Recently, it has been reported that immunoreactivity for the sialomucin CD34 may be present on ICC in human intestine. Gastrointestinal stromal tumors express both Kit and CD34, suggesting that these tumors may derive from ICC. We characterized the distribution of CD34 immunoreactivity at the cellular level in the normal human gut, using double immunofluorescence immunohistochemistry and confocal microscopy. CD34 immunoreactivity identified previously unrecognized cells closely adjacent to, but distinct from, the Kit immunoreactive ICC. These CD34 immunoreactive cells expressed the fibroblast marker prolyl 4-hydroxylase-whereas ICC did not-and were also distinct from smooth muscle cells, glial cells, and macrophages. In the human gut, CD34 immunoreactivity is not expressed by ICC but by a population of fibroblasts, likely corresponding to the "fibroblast-like cells" described in previous ultrastructural studies. Our findings also challenge the hypothesis that stromal tumors originate from ICC.

Fructans of chicory: intestinal transport and fermentation of different chain lengths and relation to fructose and sorbitol malabsorption.

Fructans (fructooligosaccharides and inulin) are of increasing interest to clinical nutritionists as functional food additives. The chemically closely related food carbohydrates fructose and sorbitol are implicated in functional bowel disease. Intestinal handling of these carbohydrates is incompletely understood. Intestinal absorption, transit, and fermentation (breath hydrogen and methane, venous acetate, blood glucose, and urine fructans) after ingestion of 10-30 g short- and long-chain fructans from chicory were studied by single-blind, crossover randomization in 10 healthy adults. Responses were compared with responses after ingestion of lactulose, fructose, and sorbitol. Breath hydrogen and venous acetate production increased in proportion to increasing fructan dose and were similar to responses to lactulose. The transit times of long-chain fructans were longer than those of short-chain fructans (75 compared with 30 min, P<0.001). Semiquantitative estimates of unabsorbed carbohydrate were not significantly different with either short-chain fructans or lactulose as nonabsorbable standards. Venous acetate curves were less precise estimates of the magnitude of carbohydrate malabsorption than were breath-hydrogen curves (P<0.01). All subjects showed malabsorption of 50 g fructose, resulting in significantly more symptoms than 20 g fructose (P<0.05). Ingestion of sorbitol with equimolar amounts of glucose did not reduce malabsorption or abdominal distress. Abdominal symptoms after fructans increased with increasing dose and decreasing chain length. The overall gastrointestinal effects of short-chain fructans seem similar to those of lactulose. Fructans with different chain lengths may have different physiologic properties and further studies of fructans in disease states are warranted.

Interstitial cells of Cajal as targets for pharmacological intervention in gastrointestinal motor disorders.

Interstitial cells of Cajal (ICCs) have recently been identified as the pacemaker cells for contractile activity of the gastrointestinal tract. These cells generate the electrical 'slow-wave' activity that determines the characteristic frequency of phasic contractions of the stomach, intestine and colon. Slow waves also determine the direction and velocity of propagation of peristaltic activity, in concert with the enteric nervous system. Characterization of receptors and ion channels in the ICC membrane is under way, and manipulation of slow-wave activity markedly alters movement of contents through the gut organs. Here Jan Huizinga, Lars Thuneberg, Jean-Marie Vanderwinden and Jüri Rumessen, suggest that, as ICCs are unique to the gut, they might be ideal targets for pharmacological intervention in gastrointestinal motility disorders, which are very common and costly.

[Strategies for investigating non-assimilation. A critical status]. / Strategier ved udredning af malassimilation. En kritisk status.

This review reevaluates the rational basis for choice of diagnostic strategies in patients with suspected malassimilation. Prospective evaluation of diagnostic tests must fulfil several requirements for a correct assessment of their clinical value. Very few studies meet such requirements, resulting in unnecessary investigations as well as overlooked cases with a negative impact on patients and society. This problem includes evaluation of assimilation of macronutrients (carbohydrate, fat, protein) as well as micronutrients (e.g. vitamin B12), and it is further complicated by the occurrence of conditions with occult (compensated) malassimilation. Malassimilation of carbohydrates may be physiological (starch, fructose, sugar alcohols etc., in certain ethnic groups lactose) as well as pathological. In both instances chronic gastro-intestinal distress may arise in sensitive individuals. The diagnosis is based on tolerance tests, combined with blood tests or breath tests (hydrogen excretion). The latter is considered the most reliable, but the available evidence for choice of tests is not solid. Similar reservations apply to conditions of bacterial overgrowth of the small intestine, which may lead to diffuse malassimilation. The frequency and clinical importance of this condition is in all probability underestimated. Screening for coeliac disease may be achieved by several serological tests (reticulin-, gliadin-, endomysial antibodies), of which IgA-endomysial antibodies seem superior. Comparative studies are often flawed in design, however, and permeability tests may also eventually find their place in the test battery. There is thus a strong need for more evidence-based diagnostic strategies in patients with suspected malassimilation.

Ultrastructure of interstitial cells of Cajal at the colonic submuscular border in patients with ulcerative colitis.

BACKGROUND & AIMS: Submuscular interstitial cells of Cajal (ICC) are putative pacemaker cells of the colonic external muscle. Although motility disturbances and smooth muscle dysfunction are prevalent in patients with ulcerative colitis (UC), ICC have never been studied in this disease. The aim of this study was to examine the ultrastructure of submuscular ICC in UC. METHODS: Transmission electron microscopy of the colonic submuscular region was performed using specimens from 4 adult patients who had undergone resection for severe UC. The specimens were compared with similarly processed control samples. RESULTS: ICC often showed multiple secondary lysosomes, large confluent lipid bodies, and disrupted aggregates of vacuolated glycogen clusters. Intermediate filaments showed margination and clumping. Intramuscular and submucosal nerve terminals were often swollen. Macrophages were frequent, often close to nerves and ICC. Muscle cells of the innermost circular layer, fibroblast-like cells, and glial cells appeared undisturbed. Other inflammatory cells were inconspicuous. CONCLUSIONS: Alterations of ICC ultrastructure are present in the submuscular pacemaker region of the colon in patients with severe UC. The changes in ICC may result from primary damage or changes secondary to defective muscular function, or they may reflect neuroimmune-mediated metabolic responses. It is suggested that ICC are actively involved in the pathogenesis of motility disturbances in UC.

Interstitial cells of Cajal in human colon and in Hirschsprung's disease.

BACKGROUND & AIMS: Subpopulations of interstitial cells of Cajal are regarded as the source of spontaneous slow waves of the gut musculature (pacemaker cells). Their ontogeny remains unclear, but a role of the tyrosine kinase receptor c-kit in their development has recently been recognized. This study examined the interstitial cells in the human colon and in Hirschsprung's disease (aganglionosis). METHODS: The distribution of the c-kit receptor was studied using specific antibodies in 5 normal patients, 10 patients with Hirschsprung's disease, and 3 patients with diversion loop enterostomies. c-kit immunohistochemistry was also combined with reduced nicotinamide adenine dinucleotide phosphate diaphorase histochemistry or with c-kit ligand (stem cell factor) immunohistochemistry. Transmission electron microscopy was performed in 1 patient with Hirschsprung's disease. RESULTS: c-kit immunoreactivity labeled a network of interstitial cells at the outer edge of the submucosa, in the muscular layers, and around the myenteric plexus. In aganglionic segments, interstitial cells were scarce and its network appeared disrupted. Interstitial cells of Cajal were identified in aganglionic regions by electron microscopy. Interstitial cells of Cajal are identifiable in newborns and exhibit similar distribution in diversion loops independent of contact with luminal nutrients. CONCLUSIONS: Our morphological data may explain the abnormal spontaneous electrical activity in aganglionic segments of Hirschsprung's disease and may give new insight into the ontogeny of interstitial cells.

Pacemaker cells in the gastrointestinal tract: interstitial cells of Cajal.

Interstitial cells of Cajal (ICC) were described a century ago as primitive neurons in the intestines. Through the years, ICC have been mistaken for neurons, glial cells, fibroblasts, smooth muscle cells, and macrophages. We identified ICC in the musculature of mouse small intestine by their characteristic morphology and topography, and we analysed the relation between ICC, autonomic nerves, and smooth muscle. Subsequent morphological and electrophysiological evidence has strongly supported our hypotheses that some ICC populations are gut pacemakers and may hold other fundamental regulatory functions (coordinative, mechanoreceptive, mediating nervous input). Recognition of common principles of ICC organization (confinement to specific locations in relation to smooth muscle layers; formation of extensive cellular networks through tight coupling of overlapping thin processes; innervation patterns; characteristic patterns of contact with smooth muscle cells) and ultrastructure (myoid features: basal lamina, caveolae, rich in sER and mitochondria, often prominent filament bundles and dense bands/bodies) has allowed the identification of ICC in the GI musculature of all species investigated. However, variation in organization and ultrastructure is significant, between both species and regions of the GI tract. Our studies of ICC in human intestine permit an extension of the above hypotheses to man and provide a basis for further studies of ICC pathology and pathophysiology. The latter may become a fruitful area of research in the coming decades.

Breath hydrogen analysis in patients with ileoanal pouch anastomosis.

The possible influence on functional outcomes of hydrogen production in the ileoanal pouch after restorative proctocolectomy was investigated by means of lactulose H2 breath tests. Eight of 15 patients had significant increases in breath hydrogen after 10 g lactulose. One patient declined to participate in further investigations, the remaining seven responders had no evidence of small bowel bacterial overgrowth after glucose H2 breath tests. The ability to produce hydrogen by anaerobic fermentation of lactulose in the pouch was unrelated to the age of the patients or of the pouch. Seven of eight responders had successive breath tests after ingestion of lactulose 20 g and wheat starch 100 g. Five of seven had significant increases after lactulose but none after wheat starch. The overall function of the pouch continence, spontaneity of defecation, and 24 hour stool frequency was significantly better in responders than in non-responders. The absence of H2 production of 100 g wheat starch may indicate either increased absorption or defective fermentation.

Intestinal transport and fermentation of resistant starch evaluated by the hydrogen breath test.

OBJECTIVE: To study fermentability of different samples of resistant starch (RS), compared to one another and to lactulose, and to study the effect on gastric emptying of addition of RS to test meal. Finally to study if adaptation to RS results in a measurable change in fermentation pattern, (H2/CH4 production). Sources of RS: Raw potato starch (RPS), 58% RS; corn flakes (CF), 5% RS; hylon VII high amylomaize starch, extrusion cooked and cooled (HAS) 30% RS; highly retrograded hylon VII high amylomaize starch (HRA) 89% RS. DESIGN: (1) Fermentation: seven healthy volunteers ingested in randomized order 50 g RPS, 100 g CF, 75 g HAS, 25 g HRA. End-expiratory H2/CH4 was measured every 30 min for 12 to 22 hours post-ingestion as a measure of fermentation. A dose-response study of RPS, 5, 10, 25, 50, 75 and 100 g was performed. (2) Adaptation: In five 3-week periods seven volunteers added daily to their usual diet 50 g of either RPS, HAS, oat bran, wheat bran or common maize starch. The polysaccharides were administered in randomized order. The test periods were separated by 1 week's wash out. Basic end-expiratory H2/CH4 was measured once a week prior to and during the test periods. (3) Gastric emptying: The rate of increase in blood glucose was measured after test meals consisting of 50 and 100 g of RPS, 50 g HAS and 50 g glucose dissolved in a gel, alone, and mixed with 25 g of RPS. As controls we chose wheat bran and oat bran. RESULTS: (1) We found that RPS is fermentable, although the cumulated excessive H2 production after 50 g RPS corresponding to 29 g RS was clearly less than after 10 g lactulose. The time from ingestion of RPS to a sustained increase in end-expiratory H2 (apparent transit time; 5-11 h) was longer than lactulose (1-4 h), indicating either a slow passage through the small intestine or a slow fermentation rate. 100 g of corn flakes (4.6 g RS) resulted in a measurable increase in H2 production, equivalent to 10-20 g RPS, whereas neither of the two samples of hylon VII high amylomaize resulted in any significant increase in H2 production. The dose-response study with RPS showed that even 5 g of RPS resulted in a measurable increase in end-expiratory H2, and increasing doses from 5 g to 100 g resulted in a seemingly exponential increase in H2 production. (2) 3 weeks' daily administration of HAS resulted in a slightly elevated increase in basic end-expiratory H2, although the increase did not reach statistical significance. RPS resulted in a sustained increase in basic end-expiratory H2. Both RS samples increased measurable end-expiratory CH4 in volunteers with measurable CH4 production after a lactulose load, but 3 weeks' daily challenge with these slowly fermentable substrates did not increase measurable CH4 in volunteers, who prior to the study only produced CH4 intermittently. (3) The rate of increase in blood sugar was unaffected by addition of RS or non-starch-polysaccharides to the test meal, indicating that addition of the polysaccharides does not affect gastric emptying. CONCLUSIONS: A fraction of RPS is resistant to digestion in the small intestine, and it is fermentable by the colonic microbial flora. RS from CF, HAS and RPS give very different H2 responses, either due to differences in digestion patterns or fermentation patterns. Short-term adaptation (3 weeks) to HAS or RPS does not change the H2/CH4 response. RS does not affect gastric emptying of a test meal consisting of glucose dissolved in a gel.

Carbohydrate malabsorption: quantification by methane and hydrogen breath tests.

BACKGROUND: Previous studies in small series of healthy adults have suggested that parallel measurement of hydrogen and methane resulting from gut fermentation may improve the precision of quantitative estimates of carbohydrate malabsorption. Systematic, controlled studies of the role of simultaneous hydrogen and methane measurements using end-expiratory breath test techniques are not available. METHODS: We studied seven healthy, adult methane and hydrogen producers and seven methane non-producers by means of end-expiratory breath test techniques. Breath gas concentrations and gastrointestinal symptoms were recorded at intervals for 12h after ingestion of 10, 20 and 30 g lactulose. RESULTS: In the seven methane producers the excretion pattern was highly variable; the integrated methane responses were disproportional and not reliably reproducible. However, quantitative estimates of carbohydrate malabsorption on the basis of individual areas under the methane and hydrogen excretion curves (AUCs) tended to improve in methane producers after ingestion of 20 g lactulose by simple addition of AUCs of methane to the AUCs of the hydrogen curves. Estimates were no more precise in methane producers than similar estimates in non-producers. Gastrointestinal symptoms increased significantly with increasing lactulose dose; correlation with total hydrogen and methane excretion was weak. CONCLUSIONS: Our study suggests that in methane producers, simple addition of methane and hydrogen excretion improves the precision of semiquantitative measurements of carbohydrate malabsorption. The status of methane production should, therefore, be known to interpret breath tests semiquantitatively. The weak correlation between hydrogen and methane excretion and gas-related abdominal complaints suggests that other factors than net production of these gases may be responsible for the symptoms.