Role of bile acids and bile acid binding agents in patients with collagenous colitis

BACKGROUND: In a retrospective study bile acid malabsorption was observed in patients with collagenous colitis. AIMS: To study the occurrence of bile acid malabsorption and the effect of bile acid binders prospectively in patients with chronic diarrhoea and collagenous colitis. METHODS: Over 36 months all patients referred because of chronic diarrhoea completed a diagnostic programme, including gastroscopy with duodenal biopsy, colonoscopy with biopsies, and the (75)Se-homocholic acid taurine ((75)SeHCAT) test for bile acid malabsorption. Treatment with a bile acid binder (cholestyramine in 24, colestipol in three) was given, irrespective of the results of the (75)SeHCAT test. RESULTS: Collagenous colitis was found in 28 patients (six men, 22 women), 27 of whom had persistent symptoms and completed the programme. Four patients had had a previous cholecystectomy or a distal gastric resection. The (75)SeHCAT test was abnormal in 12/27 (44%) of the collagenous colitis patients with (75)SeHCAT values 0.5-9.7%, and normal in 15 patients (56%). Bile acid binding treatment was followed by a rapid, marked, or complete improvement in 21/27 (78%) of the collagenous colitis patients. Rapid improvement occurred in 11/12 (92%) of the patients with bile acid malabsorption compared with 10/15 (67%) of the patients with normal (75)SeHCAT tests. CONCLUSION: Bile acid malabsorption is common in patients with collagenous colitis and is probably an important pathophysiological factor. Because of a high response rate without serious side effects, bile acid binding treatment should be considered for collagenous colitis, particularly patients with bile acid malabsorption.     

Long-term course in collagenous colitis and the impact of bile acid malabsorption and bile acid sequestrants on histopathology and clinical features.

BACKGROUND: Bile acid malabsorption is common in collagenous colitis, although long-term follow-up data on the impact of bile acids are limited. The aim was to study whether bile acid malabsorption is a permanent finding, with an impact on histopathology and clinical features in collagenous colitis. METHODS: The objective was to reinvestigate 27 patients with collagenous colitis > or = 3 years after index investigation. The clinical course was evaluated by means of an interview, a review of the hospital records and registration of symptoms over a period of 7 days. The patients were invited to undergo a repeat colonoscopy and 75SeHCAT measurement. Initial and follow-up data and 75SeHCAT values from 29 controls were compared. RESULTS: The median follow-up time was 4.2 (range 3-5.3) years. Twenty-two patients underwent a repeat 75SeHCAT test, 23 patients a colonoscopy and in 25 patients the clinical course could be evaluated. The 75SeHCAT values were abnormal in 32% at follow-up versus 44% at index, and the median retention value was 19% (range 2-69) versus 12% (range 0.5-41) (P = 0.024) although lower than in the control groups figure of 38% (range 8-91) (P < 0.005). Histopathology had improved independently of bile acid malabsorption, gender, smoking and autoimmune disease at follow-up. Four were normalized. Patients on bile acid binders had no significant change of histopathology. Four patients had recovered, seven displayed an intermittent course and 14 had continuous diarrhoea. CONCLUSIONS: Collagenous colitis and bile acid malabsorption seem to be associated yet independent disorders. The histopathology improves during the long-term course although only a few patients resolve.     

Impact of bile acid malabsorption on steatorrhoea and symptoms in patients with chronic diarrhoea

OBJECTIVE: Bile acids are important for fat absorption. The relationship between bile acid malabsorption and steatorrhoea and gastrointestinal symptoms in patients with chronic diarrhoea has only been studied on a limited scale. DESIGN: Ninety-four patients referred for chronic diarrhoea were prospectively investigated with the 75SeHCAT test, a faecal fat excretion test and registration of symptoms in addition to the standard clinical work-up. METHODS: The correlation between the 75SeHCAT value and the faecal fat excretion was calculated for different groups of patients. Symptoms were registered in a questionnaire over a period of seven consecutive days. RESULTS: Forty-two patients had a 75SeHCAT value < 10%. Mild steatorrhoea was common in patients with non-organic bile acid malabsorption (50%) and in patients with functional diarrhoea (38%). There was no correlation between low 75SeHCAT values and steatorrhoea, although some patients with severe organic disease had a concomitant malabsorption of fat and of bile acids. In coeliac disease, severe steatorrhoea was common even in patients with high 75SeHCAT values. Patients with bile acid malabsorption had more frequent (P < 0.008) and looser (P= 0.0021) stools compared with patients with functional diarrhoea. There was no difference in abdominal pain, distension or flatulence. CONCLUSION: Mild steatorrhoea is common in both non-organic bile acid malabsorption and functional diarrhoea. The 75SeHCAT value cannot predict the risk of steatorrhoea. The high prevalence of bile acid malabsorption in patients with chronic diarrhoea and the absence of specific symptoms, except frequent and more liquid stools, indicates that the 75SeHCAT test should be performed early in the investigation of these patients.     

Bile acid malabsorption investigated by selenium-75-homocholic acid taurine (SeHCAT) scans: Causes and treatment responses to cholestyramine in 298 patients with chronic watery diarrhoea

Background

The liver produces and secretes bile acids into the small intestine. In the small intestine, most of the bile acids are absorbed in the distal ileum with portal vein transportation back to the liver and resecretion (enterohepatic recycling). Increased spillover of bile acids from the small intestine into the colon (bile acid malabsorption) may affect the secretion of colonic water and electrolytes and result in watery diarrhoea.The aim of this study was to investigate the frequency of bile acid malabsorption and treatment responses to cholestyramine with ⁷⁵SeHCAT scanning among patients suffering from chronic watery diarrhoea.

Methods

This was a retrospective study that included all patients who received a ⁷⁵SeHCAT scan over a five-year period (2004-2009).

Results

In total, 298 patients (198 females, 100 men) with a median age of 42 years (range 16-82 years) were investigated.Bile acid malabsorption (⁷⁵SeHCAT retention < 15% after seven days) was identified in 201 patients (68%, 95% confidence interval (CI): 62%-73%). Bile acid malabsorption due to ileal dysfunction (Type I) was found in 77 patients, idiopathic bile acid malabsorption (Type II) was found in 68 patients and 56 patients with other conditions had bile acid malabsorption (Type III).Of the 150 patients who were able to take cholestyramine continuously, 108 patients (71%, CI: 63%-78%) reported a positive effect on their bowel habits.

Conclusions

Bile acid malabsorption is a frequent problem in patients with chronic watery diarrhoea. Treatment with bile acid binders was effective regardless of type and severity.     

Comparison of 75SeHCAT retention half-life and fecal content of individual bile acids in patients with chronic diarrheal disorders

Measurement of the retention of 23-75Se-25-homotaurocholic acid (SeHCAT) has been suggested as a new test for ileal function. We investigated 31 patients with chronic diarrhea, 10 with ileal Crohn's disease and 21 with diarrhea but without ileal disease. The whole-body retention half-life of 1 mu Ci SeHCAT was determined and compared to the fecal content of total and individual bile acids. Patients with ileal disease had increased primary fecal bile acids (chenodeoxycholic acid: mean 6.95 mg/g dry weight, range 3.15-10.6 mg/g; cholic acid: mean 18.15 mg/g, range 10.3-33.9 mg/g) and a short SeHCAT retention (mean 11.9 h, range 2-24 h), whereas patients with intact ileum had normal fecal bile acids and a SeHCAT retention of 85.9 h (range 28-216 h). SeHCAT retention half-life differentiated well between patients with ileal disease and patients with normal ileum, thus indicating the SeHCAT test as a valid investigation method for detection of primary bile acid malabsorption in patients with chronic diarrhea and ileal dysfunction.     

Clinical application of a selenium (75Se)-labelled bile acid for the investigation of terminal ileal function

With the introduction of a selenium bile acid SeHCAT (tauro-23-75Se-Selena-25 homocholic acid) a new and clinically valuable test for the functioning of the terminal ileum has been made available. Previous studies have shown that the test detects patients with bile acid malabsorption due to ileal disease. In this study SeHCAT retention was evaluated in nine patients with Crohn's disease and in seven healthy controls after intravenous administration of 0.15 MBq (4 muCi). A simple way of expressing the results is proposed. By using the calculated time required to eliminate 50% of the SeHCAT (WBR50), information is obtained as to the degree of terminal ileum malfunction regarding bile acid absorption. Accurate values seem to be achieved within 48 hours. As the SeHCAT is a gamma-ray emitter the dose retained could be measured by external counting. We suggest a practical design for the test using a simple scintillation spectro-photometer with a single detector in a low-background room. In patients and healthy controls the SeHCAT retention as calculated by WBR50 was 63 hrs (15-163) and 120 hrs (range 99-141), respectively. There was no overall relation between SeHCAT elimination and the intestinal transit time, although in the patient group a significant correlation was demonstrated, probably secondary to the impairment of the terminal ileum. A significant correlation was shown between the outcome of the test and the faecal excretion of total bile acids.     

Comparison of maximal postprandial serum cholylglycine concentration with the retention of 75Se-homotaurocholic acid in ileal dysfunction

The retention of 75Se-homotaurocholic acid (75SeHCAT) was measured in 12 healthy controls and in 21 patients with Crohn's disease and compared with the maximum postprandial rise in the serum concentration of cholylglycine (CG) in order to detect bile acid malabsorption. The retention of 75SeHCAT was lowered in all patients with inflammation or resection of the terminal ileum over a length more than 20 cm. In 64% of these patients bile acid malabsorption could also be detected by the absence of a significant rise of the postprandial CG serum level but only if the loss of the ileal function exceeded 30 cm. Although less sensitive than the 75SeHCAT retention, the CG method is simpler to apply in terms of laboratory technology and does not involve exposure to radioactivity. The CG method appears to be of use to detect bile acid malabsorption in certain cases. In the case of negatively if still bile acid malabsorption is suspected more sensitive tests such as 75SeHCAT retention should be carried out to further evaluate bile acid malabsorption.     

Long-term Course in Collagenous Colitis and the Impact of Bile Acid Malabsorption and Bile Acid Sequestrants on Histopathology and Clinical Features

Background: Bile acid malabsorption is common in collagenous colitis, although long-term follow-up data on the impact of bile acids are limited. The aim was to study whether bile acid malabsorption is a permanent finding, with an impact on histopathology and clinical features in collagenous colitis. Methods:     

75Se HCAT test in the detection of bile acid malabsorption in functional diarrhoea and its correlation with small bowel transit.

The purpose of this study was to evaluate whether bile acid malabsorption assessed by the 75SeHCAT test, had a pathogenetic role in functional chronic diarrhoea and to ascertain whether the small bowel transit time (SBTT) could be correlated with the 75SeHCAT test results. The test was based on the counting of the abdominal retention of a 75-selenium labelled homotaurocholic acid. The 75SeHCAT test was carried out in a control group of 23 healthy adults and in 46 patients, 38 of whom were suffering from irritable bowel syndrome (IBS) of diarrhoeic form and eight patients who had undergone cholecystectomy and were suffering from chronic diarrhoea. Faecal bile acid loss was determined in nine patients, and in 14, serum bile acid increase after a standard meal was measured. In 17, SBTT was studied by hydrogen breath test after lactulose administration (21 g in 300 ml water). In 15 patients, choledochocaecal transit time was estimated by Tc99m-HIDA (111 MBq) cholescintigraphy. In 20 of 46 subjects, 75SeHCAT retention was below normal level, and in 19 cholestyramine administration relieved diarrhoea. 75SeHCAT results were related to faecal bile acid loss, while no correlation was found with serum bile acids and SBTT. The data suggest a possible wider use of the 75SeHCAT test in chronic diarrhoea to estimate bile acid malabsorption in irritable bowel syndrome, diarrhoeic form, and provide an effective treatment. In our patients small bowel transit velocity does not seem to be a pathogenetic factor of bile acid malabsorption.     

Bile acid malabsorption after intestinal bypass surgery for obesity. A comparison between jejunoileal shunt and biliointestinal bypass

Seventeen patients were operated on with intestinal shunts for morbid obesity, in eight a biliointestinal bypass (BI) was constructed and in the rest a conventional jejunoileal (JI)-shunt. The reduction in weight was similar in both groups, and so was malabsorption of fat, but the BI-group had significantly less bowel motions with less watery diarrhoea. Bile acid malabsorption was measured both chemically by estimating the total amount of faecal bile acids excreted, as well as indirectly by using a 75Se-labelled synthetic bile acid (SeHCAT). Both techniques revealed a substantial loss of bile acid after both types of operation, but patients with BI bypass surgery had significantly lower elimination time of the bile acid than those with JI-shunts. There was a significant negative correlation between SeHCAT retention and total faecal bile acids. However, some patients with low SeHCAT retention had normal or even reduced output of faecal bile acids. Estimation of faecal bile acids may display false negative results when the bile acid pool is decreased. The SeHCAT-test seems to be a better technique for measuring bile acid losses. The study suggests that BI bypass surgery for obesity seems to be advantageous over the JI shunt in reducing the postoperative loss of bile acids and choleretic diarrhoea, without influencing the weight loss.     

Bile acid malabsorption caused by gastrointestinal motility dysfunction? An investigation of gastrointestinal disturbances in familial amyloidosis with polyneuropathy.

Gastrointestinal dysfunction due to autonomous neuropathy is a complication described in various diseases such as diabetes mellitus, multiple sclerosis, and familial amyloidosis with polyneuropathy. We present the results of a prospective investigation of bile acid malabsorption in 17 patients with familial amyloidosis by means of 75Se-labelled homocholic-tauro acid (SeHCAT). The diagnosis was in all cases verified by the DNA test for mutation of transthyretin in position 30. Small-intestinal biopsy specimens were examined for deposits of amyloid, and the presence of gastric retention was evaluated by gastroscopy. In addition, the patients were investigated for bacterial overgrowth by means of the bile acid breath test (BABT). A high frequency of abnormal BABT results (44%) was encountered. However, 65% also had abnormal low SeHCAT values, indicating bile acid malabsorption. Only two patients had abnormal BABT and normal SeHCAT results, indicating bacterial contamination of the small intestine. Bile acid losses increased with the duration of gastrointestinal symptoms. Significantly lower SeHCAT values were encountered in patients with gastric retention, whereas the occurrence of amyloid deposits in small-intestinal biopsy specimens was without effect on SeHCAT retention. Bile acid malabsorption is frequently encountered in familial amyloidosis with polyneuropathy and seems to be more closely associated with gastrointestinal motility dysfunction than with amyloid deposits in the intestinal mucosa.     

Colonic epithelial cell turnover: possible implications for ulcerative colitis and cancer initiation

Gastrointestinal dysfunction due to autonomous neuropathy is a complication described in various diseases such as diabetes mellitus, multiple sclerosis, and familial amyloidosis with polyneuropathy. We present the results of a prospective investigation of bile acid malabsorption in 17 patients with familial amyloidosis by means of ⁷⁵Se-labelled homocholic-tauro acid (SeHCAT). The diagnosis was in all cases verified by the DNA test for mutation of transthyretin in position 30. Small-intestinal biopsy specimens were examined for deposits of amyloid, and the presence of gastric retention was evaluated by gastroscopy. In addition, the patients were investigated for bacterial overgrowth by means of the bile acid breath test (BABT). A high frequency of abnormal BABT results (44%) was encountered. However, 65% also had abnormal low SeHCAT values, indicating bile acid malabsorption. Only two patients had abnormal BABT and normal SeHCAT results, indicating bacterial contamination of the small intestine. Bile acid losses increased with the duration of gastrointestinal symptoms. Significantly lower SeHCAT values were encountered in patients with gastric retention, whereas the occurrence of amyloid deposits in small-intestinal biopsy specimens was without effect on SeHCAT retention. Bile acid malabsorption is frequently encountered in familial amyloidosis with polyneuropathy and seems to be more closely associated with gastrointestinal motility dysfunction than with amyloid deposits in the intestinal mucosa.     

Use of 23-selena-25-homocholyltaurine to detect bile acid malabsorption in patients with illeal dysfunction or diarrhea

Abdominal gamma-counting after oral administration of 23-selena-25-homocholyltaurine (75SeHCAT) was carried out on 23 healthy volunteers and 66 patients: 33 with distal ileum resections, 3 with Crohn's disease of the ileum, 17 suffering from various intestinal diseases but with normal ileum, and 13 with chronic diarrhea syndrome but without evident intestinal or extraintestinal pathology. The percentage value of 75SeHCAT abdominal retention was assessed by analysis of the activity versus time curve, obtained by single exponential least-squares fit in five consecutive measurements (time zero and 1, 3, 5, and 7 days after 75SeHCAT administration) and directly by the gamma-camera countings on days 3, 5, and 7. The percentage values obtained from the curve on the third day were found to be the most suitable for differentiating between the groups, giving the 75SeHCAT test a 94% sensitivity and a 100% specificity. Our data show that this test is a valid indicator of bile acid loss: actually, it gave evidence of idiopathic malabsorption of bile salts in 6 patients with diarrhea of unknown origin who responded to cholestyramine and showed a correlation (correlation index = 0.585) with the residual ileum of the last meter in resected patients. Moreover, the 75SeHCAT test is easy to perform in any hospital with gamma-counting facilities and has negligible radiation risk.     

Bile Acid Malabsorption in Patients with Chronic Diarrhoea

The presence of bile acid malabsorption was studied in 24 patients with chronic diarrhoea without established cause despite extensive investigations. Bile acid absorption was evaluated with the ⁷⁵Se-homocholic acid taurine (SeHCAT) test. A therapeutic trial of cholestyramine was performed in 11 patients. Fourteen of the patients (58%) showed evidence of bile acid malabsorption. Of the 11 patients who were treated with cholestyramine, 3 had no improvement of their diarrhoea and also had a normal SeHCAT test result. Of the other eight patients, who also had pathologic SeHCAT test result, five improved on treatment, whereas three had no change of their diarrhoea. Seven of the 24 patients had a previous history of cholecystectomy. Four of them showed bile acid malabsorption; three of these were treated with cholestyramine and responded favourably. The results suggest that bile acid malabsorption may be common in chronic diarrhoea patients but may not always be the primary cause of diarrhoea.     

Normal or increased bile acid uptake in isolated mucosa from patients with bile acid malabsorption

INTRODUCTION: Bile acid malabsorption as reflected by an abnormal Se-labelled homocholic acid-taurine (SeHCAT) test is associated with diarrhoea, but the mechanisms and cause-and-effect relations are unclear. OBJECTIVES: Primarily, to determine whether there is a reduced active bile acid uptake in the terminal ileum in patients with bile acid malabsorption. Secondarily, to study the linkage between bile acid malabsorption and hepatic bile acid synthesis. METHODS: Ileal biopsies were taken from patients with diarrhoea and from controls with normal bowel habits. Maximal active bile acid uptake was assessed in ileal biopsies using a previously validated technique based on uptake of C-labelled taurocholate. To monitor the hepatic synthesis, 7alpha-hydroxy-4-cholesten-3-one, a bile acid precursor, was assayed in blood. The SeHCAT-retention test was used to diagnose bile acid malabsorption. RESULTS: The taurocholate uptake in specimens from diarrhoea patients was higher compared with the controls [median, 7.7 (n=53) vs 6.1 micromol/g per min (n=17)] (P<0.01) but no difference was seen between those with bile acid malabsorption (n=18) versus diarrhoea with a normal SeHCAT test (n=23). The SeHCAT values and 7alpha-hydroxy-4-cholesten-3-one were inversely correlated. CONCLUSIONS: The data do not support bile acid malabsorption being due to a reduced active bile acid uptake capacity in the terminal ileum.     

Serum 7 alpha-hydroxy-4-cholesten-3-one concentrations in the evaluation of bile acid malabsorption in patients with diarrhoea: correlation to SeHCAT test.

The synthesis of bile acids is regulated by a homeostatic mechanism in which bile acids returning to the liver from the intestine inhibit their own synthesis. Serum concentrations of the bile acid intermediate 7 alpha-hydroxy-4-cholesten-3-one reflect the rate of bile acid synthesis whereas bile acid malabsorption can be determined by the SeHCAT test. This study was done to evaluate the correlation between the two tests in humans. Twenty eight patients with chronic diarrhoea were included in the study. Fasting serum was collected for the determination of 7 alpha-hydroxy-4-cholesten-3-one, and on the same day the gamma emitting bile acid analogue SeHCAT was given orally and its fractional catabolic rate assessed by repeated external counting over the upper abdomen during the next seven days. There was a highly significant positive correlation between the two tests (Rs = 0.80, p < 0.001). The results show a close relation between intestinal loss and hepatic synthesis of bile acids and imply that analysis of 7 alpha-hydroxy-4-cholesten-3-one in serum should now be evaluated as a possible convenient method for assessing bile acid malabsorption in patients with diarrhoea.     

Chronic diarrhoea after radiotherapy for gynaecological cancer: occurrence and aetiology.

The occurrence of chronic diarrhoea was evaluated in 173 consecutive patients previously treated with radiation for gynaecological cancer. A survey of gastrointestinal symptoms showed a high frequency of diarrhoea; 13% of the patients had 21 or more bowel movements a week and 3% had 28 or more. Significantly more patients who had a cholecystectomy were in the group with diarrhoea (chi 2 = 6.26; p less than 0.02). Twenty patients with chronic or intermittent diarrhoea were subject to extended gastrointestinal investigation. Bile acid malabsorption was evaluated by the 75Selenahomocholic acid-taurine test (SeHCAT). Bile acid malabsorption was found in 13 (65%) of the 20 patients further investigated, of whom seven had extremely low whole body retention values, which is consistent with severe malabsorption. The results suggest that bile acid malabsorption is a common cause of diarrhoea after radiation treatment for gynaecological cancer. Bacterial contamination was diagnosed in nine patients (45%) by the [14C]-D-xylose breath test or by the cholyl-[14C]-glycine breath test in combination with a normal test for bile acid malabsorption. All patients with vitamin B-12 deficiency, who were tested for bile acid malabsorption, had low retention times for the SeHCAT (p = 0.05). A significant decline in the frequency of diarrhoea was found after treatment with antibiotics or bile acid sequestrants, or both, in combination with a reduced fat diet.     

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 &#83 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.     

Bile acid malabsorption in Crohn's disease and indications for its assessment using SeHCAT.

Patients with Crohn's disease who suffer from longstanding diarrhoea that does not respond to conventional treatment pose a common clinical problem. Bile acid malabsorption is a possible cause, although its prevalence and clinical importance is unclear. This paper explores the clinical indications for referring patients with Crohn's disease for bile acid assessment and the extent of bile acid malabsorption in this selected group of patients. The selenium labelled bile acid SeHCAT was used to assess the effect of disease on the integrity of the enterohepatic circulation. Altogether 76% of the patients referred for bile acid assessment had longstanding diarrhoea that had not responded to conventional anti-diarrhoeal treatment or an increase in steroid therapy as their sole or predominant symptom. Ninety per cent of patients with bowel resections, almost exclusively ileocaecal, had abnormal SeHCAT retention (< 5% at seven days). Twenty eight per cent of patients with Crohn's disease who had not undergone resection 28% had a SeHCAT retention < 5%, signifying bile acid malabsorption. Nineteen of 22 patients given cholestyramine treatment subsequent to the SeHCAT test had a good symptomatic response. In conclusion, the prevalence of bile acid malabsorption in this selected group with Crohn's disease is sufficiently high to justify performing the SeHCAT test in order to separate the various differential diagnoses.     

Reversible functional disorders of the intestinal tract caused by abdominal radiotherapy

In 20 patients with malignancies receiving abdominal radiotherapy, tests for disturbed intestinal functions were performed at the beginning and at the end of the therapy and after 6 to 12 month following radiation. Four noninvasive tests were performed: 75Se-homotaurocholate (75SeHCAT) test for estimation of bile acid malabsorption; Schillings test for quantification of vitamin B12 absorption; H2-breath analysis before and after a test meal containing lactose as a parameter of lactose malabsorption; and 51Cr-EDTA test for estimation of intestinal permeability. Both bile acid and vitamin B12 absorption decreased significantly towards the end of abdominal radiotherapy in more than 50% of patients. Only one patient developed lactose malabsorption. After 6 to 12 month, these abnormalities had completely disappeared. In contrast, small intestinal permeability did not increase during radiotherapy but was significantly elevated 6 to 12 month following treatment as the only indication of chronic injury of small intestinal mucosa. During radiotherapy, a significant correlation existed between the severity of diarrhea and the degree of bile acid malabsorption.