Relationship between bile acid malabsorption and pancreatic insufficiency in cystic fibrosis.

Weber, Andrée; Roy, Claude; Chartrand, L; Lepage, Guy; Dufour, O.; Morin, Claude; Lasalle, R

doi:10.1136/gut.17.4.295

Cited by 98 publications

(55 citation statements)

References 17 publications

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“…In 2 patients without steatorrhoea we found bile acid excretions within control limits, and this has also been found by other workers (Weber et al, 1976). Normal excretion in patients retaining some pancreatic function suggests that the excessive bile acid loss usually found in CF is not a primary manifestation of the basic defect but is in some way associated with the fat malabsorption.…”

Section: Discussionsupporting

confidence: 88%

“…About 15% of CF patients retain sufficient pancreatic enzyme secretory function to prevent steatorrhoea. As far as we can ascertain from wide inquiry and from clinical experience, portal hypertension and cirrhosis are not seen in such patients without steatorrhoea and who have been shown by Weber et al (1976) and by ourselves not to be losing bile acids. Furthermore, hepatic fibrosis is associated with bile acid loss and altered bile acid metabolism in adults with ileal bypass for morbid obesity (Bagheri et al, 1974;Sherr et al, 1974 Control data for faecal bile acid excretion were determined in our own laboratory from 11 healthy children, 5 boys and 6 girls, aged from 6 months to 13-8 years, mean age 6 3 years (Goodchild et a!., 1975 the diet record varied from 1 * 2 g-5 * 6 g fat/kg body weight per day.…”

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confidence: 78%

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Reduction of bile acid loss in cystic fibrosis by dietary means.

Smalley¹,

Brown²,

Parkes³

et al. 1978

Archives of Disease in Childhood

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SUMMARY On a 'normal' diet increased faecal bile acid excretion was found in 14 of 16 children with cystic fibrosis who had steatorrhoea, but excretion was normal in 2 such children without steatorrhoea. The 16 children with steatorrhoea took 3 regimens of diet and therapy: a 'normal' diet with pancreatic enzyme supplements, a diet of reduced long-chain triglycerides with added mediumchain triglycerides, and the same diet with added pancreatic enzyme supplements. On each of these three regimens steatorrhoea and faecal bile acid loss were significantly less than on no treatment, with the lowest excretions occurring on the diet of reduced long-chain triglycerides with added medium-chain triglycerides and pancreatic enzyme supplements. Although a reduction in steatorrhoea was nearly always accompanied by a decrease in bile acid excretion, the initial bile acid loss was very variable and could not be predicted for any given degree of steatorrhoea. This suggests that at least one other factor, possibly liver disease or bile acid pool size, influences bile acid loss in the faeces.

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Section: Discussionsupporting

confidence: 88%

mentioning

confidence: 78%

Reduction of bile acid loss in cystic fibrosis by dietary means.

Smalley¹,

Brown²,

Parkes³

et al. 1978

Archives of Disease in Childhood

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“…The relationship of fecal bile acid output to dietary fat intake may be partly explained by changes in fecal fat output. Weber et al (49,50) have shown in children with malabsorption that bile acid excretion is related to fecal fat excretion.…”

Section: Discussionmentioning

confidence: 99%

“…How this increase in fecal fat might influence the change in fecal bile acid output is not clear. Long chain fatty acids are said to inhibit bile acid reabsorption in the terminal ileum (56) but Weber et al (50) have suggested that fecal triglycerides are more important than total fecal fat output in determining bile acid excretion in children with malabsorption. Increased fat intake however might mean simply a small increase in fat not absorbed in the small bowel on the basis that a constant (although high) proportion of dietary fat is absorbed.…”

Section: Discussionmentioning

confidence: 99%

Influence of diets high and low in animal fat on bowel habit, gastrointestinal transit time, fecal microflora, bile acid, and fat excretion.

Cummings¹,

Wiggins²,

Jenkins³

et al. 1978

J. Clin. Invest.

201

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A B S T R A C T Epidemiological observations and animal experiments suggest that large bowel cancer is related to several factors. Among them, high dietary intakes of animal fat, the presence in the colon of relatively high levels of bile acids, specific patterns of intestinal microflora, slow transit through the gut, and low stool weights. Under metabolic conditions we have observed the effect on these variables of diets containing 62 or 152 g/day of fat mainly of animal origin in six healthy young men over 4-wk periods. No change attributable to the diet was observed in the subjects' bowel habit, fecal weight, mean transit time through the gut, or in the excretion of dry matter. Total fecal bile acid excretion was significantly higher on the high fat diet (320±+120 mg/day) than on the low fat diet (139.7 +63 mg/day) t test = 7.78 P < 0.001 as also was the total fecal fatty acid excretion, 3.1+0.71 and 1.14±0.35 g/day, respectively t test = 11.4 P < 0.001). The fecal microflora including the nuclear dehydrogenating clostridia were unaltered by the dietary changes as was fecal /3-glucuronidase activity. Dietary changes which increase animal fat intake clearly influence fecal bile acid excretion in a way that would favor the development of large bowel cancer if current theories prove to be true. Dietary fat however has no effect on overall colonic function so other components of the diet must be responsible for the observed associations of bowel cancer with slow transit and reduced fecal bulk.

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“…The bile acid recirculation is disturbed, resulting in an increased faecal loss (8), probably due to a disorder of the absorption in the terminal ileum (2). This may lead to a reduction of the bile acid pool as well as a decreased excretion of bile acid in the duodenum.…”

Section: Bile Acidsmentioning

confidence: 99%

Problems in the treatment of malabsorption in CF

1985

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). Problems in the treatment of malabsorption in CF. Acta Paed Scand Suppl 317.Several factors play a role in the cause of malabsorption in CF. Besides the enzyme deficiency in the secretion of the exocrine pancreas, decreased bile-salt concentration in the gut may also be an important factor in the fat malabsorption. The contribution to the fat absorption by other lipases, such as lingual lipase and gastric lipase, remains to he proved. The therapeutic measures are only partly effective because of the breakdown of swalled enzymes by gastric acid. Some improvement is reached by using a new acid-resistant coating for the enzyme supplement. Newly developed and essential for its success is the application of small coated particles to prevent retention in the stomach, and the easy breakdown of the coating in an alkaline solution. The treatment of the bile salt deficiency has not been successful until now. A trial with additional Tween 80, with the option of supplementing the detergent activity which was found to he successful in Crohn disease, was without marked success.Malabsorption is one of the more serious problems in CF. The fat and protein digestion and absorption and, to a lesser extent, also the carbohydrate digestion are disturbed. The disorder of the intraluminal digestion is caused mainly by insufficiency of the exocrine pancreas, in particular by the decreased secretion of bicarbonate, lipase and trypsin. Moreover, the digestion is disturbed by a deficiency of bile salts in the proximal gut which results in a reduced emulsifying capacity and a decrease in enzyme induction.The supposed high viscosity of the intestinal fluids may hamper the transport of digested products. This would explain many of the CF-related disorders, such as intestinal obstruction and ileus symptoms and the thick unstirred water layer on the brushborder of the epithelium (1). Finally, a specific intracellular transport defect of bile salts has recently been suggested (2).In the following survey, we consider the role of these factors in C F patients. EnzymesIn the majority of C F patients, pancreatic enzyme deficiency is such that both fat and protein absorption is seriously diminished. The main enzymes involved are lipase, the lipase-colipase complex, lingual lipase, phospholipase, and the protein and carbohydrate splitting enzymes. This was repeatedly shown, among others, by Wong et al. (3) using the pancreozymin secretin stimulation test. Their results revealed that the enzyme activity of lipase reached only 3 % of normal levels, whereas trypsin and chymotrypsin amounted to 30 %. However, the usual treatment consisting of the administration of supplemental pancreas extract is only partly effective. Fat absorption does improve, but without reaching a normal level. In this connection, DiMagno et al. (4) carried out a study of enzyme activity in the duodenum following the administration of pancreatic extracts. In the distal part of the duodenum, this resulted in 22% of the administered dose for trypsin activity and only 3 % for the l...

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Relationship between bile acid malabsorption and pancreatic insufficiency in cystic fibrosis.

Cited by 98 publications

References 17 publications

Reduction of bile acid loss in cystic fibrosis by dietary means.

Reduction of bile acid loss in cystic fibrosis by dietary means.

Influence of diets high and low in animal fat on bowel habit, gastrointestinal transit time, fecal microflora, bile acid, and fat excretion.

Problems in the treatment of malabsorption in CF

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