Intestinal bacterial flora and bile salt studies in hypogammaglobulinaemia

Five patients with adult acquired hypogammaglobulinaemia, four of whom were achlorhydric, were studied. Jejunal bacterial counts were much higher than those in a control group of acid secretors, but were similar to those in a control group of patients with pernicious anaemia; Giardia lamblia were isolated from the jejunal content of all patients with hypogammaglobulinaemia. The concentration of conjugated bile acids in the fasting state was lower in hypogammaglobulinaemia than in pernicious anaemia, but in the two hypogammaglobulinaemic patients with steatorrhoea there was a normal bile salt response to a fatty meal.     

Primary bile acid malabsorption. Histologic and immunologic study in three patients

Three patients are presented with a history of chronic watery diarrhea due to bile acid malabsorption, proved by the tauro-23[75Se]selena-25 homocholic acid test and an unequivocal response to cholestyramine therapy. Fecal fat tests, Schilling tests, and barium studies of the small intestine and colon were all normal. Jejunal biopsies were normal but multiple biopsies of the terminal ileum, performed by retrograde ileoscopy, showed uniform crypt hyperplastic villous atrophy and features of colonic metaplasia with increased mononuclear infiltration of the lamina propria. All 3 patients demonstrated evidence of abnormal immune function, including the presence of serum autoantibodies, circulating immune complexes, and hypocomplementemia. One patient had Sj?gren's syndrome. This disorder, which might be immunologically mediated, should be called primary bile acid malabsorption and should be distinguished from other ileal disorders.     

Risk of giardiasis in Aucklanders: a case-control study.

BACKGROUND: Giardia is one of the leading protozoal causes of human gastrointestinal illnesses. It is prevalent in both developed and developing countries. Currently, giardiasis is the most commonly notified waterborne disease in New Zealand. The aim of the study was to identify potentially modifiable risk factors for Giardia infection in the adult population in Auckland. METHODS: This case-control study involved 183 Giardia-positive cases and 336 randomly selected controls, aged between 15 and 64 years. Exposure information was collected retrospectively over the telephone for the 21 days preceding the date of onset of symptoms. Both univariate and multiple logistic regression analyses were carried out. RESULTS: The majority of cases were in the 25-44-year age group and in the New Zealand European ethnic group. Housewives and nursing mothers were at significant risk of the disease (odds ratio (OR)=2.06; 95% CI=1.4-3.74), as were the occupational groups exposed to human wastes (OR=4.04, 95% CI=1.85-8.85). Consumption of drinking water from New Zealand supplies other than metropolitan mains supplies (OR=2.11, 95% CI=1.36-3.27) or from sources outside New Zealand (OR=7.97, 95% CI=4.20-15.12) represented a significantly higher risk, as did traveling (OR=7.57, 95% CI=4.03-14.23) and swimming in pools or fresh water at least once a week (OR=2.04, 95% CI= 1.33-3.12). CONCLUSIONS: The study identified potentially modifiable risk factors for Giardia infection. These findings should be investigated further in different groups and settings to ensure better protection of the public health.     

Differential effects of metformin on bile salt absorption from the jejunum and ileum

Aims: The antidiabetic drug metformin is often associated with a small reduction in total circulating cholesterol, but the mechanism responsible is unknown. As bile salts contribute significantly to cholesterol homeostasis, this study has investigated the effect of metformin on the absorption of bile salts by the jejunum and ileum, and their transfer into bile.
Methods: Sodium-[1-¹⁴C]-glycocholate was administered into the jejunum or ileum of anaesthetized rats with and without metformin (250 mg/kg). Appearance of ¹⁴C-glycocholate in plasma and bile was followed for 150 min.
Results: Absorption of ¹⁴C-glycocholate from the ileum, which is a high-capacity active process, was 10-fold greater than absorption from the jejunum, which is mainly a passive process. Metformin increased threefold the absorption of ¹⁴C-glycocholate from the jejunum. Metformin similarly increased the appearance of jejunal ¹⁴C-glycocholate in plasma and bile. In contrast to the jejunum, absorption of ¹⁴C-glycocholate from the ileum was suppressed by more than half with metformin. This was associated with corresponding reductions of ¹⁴C-glycocholate in plasma and bile.
Discussion: Thus, metformin induced a large suppression of active bile salt absorption from the ileum compared with a small increase in passive absorption from the jejunum. This suggests that the ileal effect of metformin to reduce overall bile salt absorption could contribute to the modest cholesterol-lowering effect of this drug.     

Diagnostic value of serum primary bile acids in detecting bile acid malabsorption.

Serum cholic and chenodeoxycholic acid conjugates were measured in fasting conditions and after meals in 14 patients with bile acid malabsorption due to ileal resection. Mean serum fasting levels of both primary bile acids did not differ from the controls. After meals, serum cholic acid peaks were lower in patients with ileal resection than in control subjects (p less than 0.001), while chenodeoxycholic acid peaks were reduced in colectomised patients (p less than 0.01). In the sera from patients with ileal resection, the glycine/glycine + taurine ratio for cholic and chenodeoxycholic acid increased (p less than 0.001) from morning to evening, and glycine/glycine + taurine ratio for chenodeoxycholic acid was significantly (p less than 0.01) different from the controls in the sera collected in the evening. The results are consistent with the concept of a better intestinal conservation of chenyl, mainly of the glycine conjugated from, than of cholylconjugates, in patients with ileal resection; this is probably because of passive absorption in the intestine. The postprandial peaks of serum cholic acid conjugates may therefore be regarded as a test of ileal dysfunction, while peaks of chenodeoxycholic acid conjugates suggest colonic impairment.     

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

Bile acid loss (mg/m2 24h) in the stools of 43 cystic fibrosis (CF) children with pancreatic insufficiency was 751-1 +/- 48-3, while that of six without clinical evidence of pancreatic disease (133-4 +/- 15-9) did not differ from values in 25 controls (109-8 +/- 9-8). There was a good correlation between the degree of bile acid (BA) and fat sequestration. Concomitant changes in bile acid and fat loss were observed in the one group of six patients studied on and off pancreatic enzymes as well as in a second group of seven children treated with pancreatic supplements and maintained on a normal diet followed by a low fat diet supplemented with medium chain triglycerides. Administration of NA bicarbonate led to a significant decrease in fat loss (15-8 +/- 2-7 leads to 10-3 +/- 1-9) without any simultaneous change in bile acid excretion (533-1 +/- 58-3 leads to 500-4 +/- 58-6). Qualitative bile acid patterns in controls, in infants after an ileal resection, and in patients with CF or with coeliac disease showed that the percentage of primary BA followed closely the total amount excreted except in situations where antibiotics were administered. The exact mechanism for the increased loss of BA in CF is unknown. It is found in all age groups and is related to the presence and degree of pancreatic insufficiency. The possibility that unhydrolysed triglycerides may interfere with the intestinal absorption of bile acid needs further confirmation.     

Apparent selective bile acid malabsorption as a consequence of ileal exclusion: effects on bile acid, cholesterol, and lipoprotein metabolism.

A new model has been developed to characterise the effect of a standardised ileal exclusion on bile acid, cholesterol, and lipoprotein metabolism in humans. Twelve patients treated by colectomy and ileostomy for ulcerative colitis were studied on two occasions: firstly with a conventional ileostomy and then three months afterwards with an ileal pouch operation with an ileoanal anastomosis and a protective loop ileostomy, excluding on average 95 cm of the distal ileum. The ileostomy contents were collected during 96 hours and the excretion of bile acids and cholesterol was determined using gas chromatography-mass spectrometry. Fasting blood and duodenal bile samples were collected on two consecutive days. After the exclusion of the distal ileum, both cholic and chenodeoxycholic acid excretion in the ileostomy effluent increased four to five times without any change in cholesterol excretion. Serum concentrations of lathosterol (a marker of cholesterol biosynthesis) and 7 alpha-hydroxycholesterol (a marker for bile acid biosynthesis) were increased several fold. Plasma concentrations of total VLDL triglycerides were also increased whereas the concentrations of total and LDL cholesterol, and apolipoprotein B were decreased. There were no changes in biliary lipid composition or cholesterol saturation of bile. The results show that the exclusion of about 95 cm of distal ileum causes malabsorption of bile acids but apparently not of cholesterol. The bile acid malabsorption leads to increased synthesis of both bile acids and cholesterol in the liver. It is suggested that bile acids can regulate cholesterol synthesis by a mechanism independent of the effect of bile acids on cholesterol absorption. The enhanced demand for cholesterol also leads to a decrease in plasma LDL cholesterol and apolipoprotein B concentrations. The malabsorption of bile acids did not affect biliary lipid composition or cholesterol saturations of VLDL triglycerides.     

Role of bacterial toxins,bile acids,and free fatty acids in colonic water malabsorption in tropical sprue

Colonic perfusion studies in 10 southern Indian patients with tropical sprue and nine matched healthy adults revealed a defect of water and sodium absorption from the colon in sprue. Heat-labile and heat-stable enterotoxin production was not detected in coliforms cultured from the feces of any of the 19 subjects. The 24-hr fecal bile acid output was increased in patients with sprue, but fecal aqueous bile acid concentrations remained within normal limits, and these did not correlate with defects in colonic water and sodium absorption. Fecal free fatty acid excretion was markedly increased in sprue. There was a negative correlation between fecal excretion of unsaturated free fatty acids and colonic water and sodium absorption.     

A study of malabsorption after resection of the entire jejunum and the proximal half of the ileum

Biochemical, haematological, and radiological investigations are reported in a young child in whom nearly 80% of the small intestine was resected. The prognosis in a child after such extensive resection is probably better than in an adult, as natural growth can still occur with the expectation of greater adaptability as well as of increased length of the remaining segments.     

Adaptive regulation of hepatic bile salt transport. Effect of prolonged bile salt depletion in the rat

Exposure of the liver to increased bile salt flux can increase the bile salt maximum secretory rate (SRm), presumably through the induction of new transport sites. The converse, i.e., the down-regulation of SRm upon bile salt deprivation, has not been demonstrated. We examined the effects of bile salt depletion for 24 h and 48 h on taurocholate SRm and bromsulphalein (BSP) SRm, and on [14C]taurocholate binding to isolated liver surface membranes in unrestrained external biliary fistula rats. Taurocholate SRm was significantly decreased by 35% and 51% in 24-h-depleted and 48-h-depleted rats, respectively, compared with control, sham-operated rats. Maximal taurocholate concentration in bile was also significantly lower in bile salt-deprived rats. In contrast, BSP SRm was not significantly different between depleted animals and controls. Bile salt depletion for 24 h and 48 h did not significantly alter liver surface membrane protein recovery and membrane enzyme specific activity, including Na+ + K+-ATPase. Specific [14C]taurocholate binding to liver surface membranes was significantly decreased by 25% in 24-h-depleted rats compared with control rats. In contrast to taurocholate SRm, bile salt depletion for 48 h did not result in further reduction of specific taurocholate binding sites. This study demonstrates that taurocholate SRm progressively decreased in 24-h- and 48-h-bile salt-depleted rats, this being consistent with adaptive down-regulation of hepatic bile salt transport.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression of bacterial beta-glucuronidase in human bile: an in vitro study

BACKGROUND: Bacterial beta-glucuronidase causes deconjugation of bilirubin diglucuronide resulting in the precipitation of calcium bilirubinate, which contributes to biliary sludge and stone formation. This process is attributed to enzyme activity produced by the aerobic enterobacteriaceae such as Escherichia coli and Klebsiella sp. The presence of Clostridium sp. was detected in 48 of 56 intrahepatic stones by using polymerase chain reaction techniques and cultured Clostridium perfringens from 14 of 18 unblocked biliary stents. Such bacteria are reported to produce beta-glucuronidase activity. The aim of this study was to determine the proportion of biliary bacteria isolated from pigment stones and stents that produce beta-glucuronidase and to compare the enzyme activity expressed by the different bacteria in human bile. METHODS: A total of 202 bacteria were isolated from blocked and unblocked biliary stents and pigment ductal stones recovered from patients. Of these, 61 bacteria expressed beta-glucuronidase activity in brain heart infusion broth. These 61 bacteria were subsequently grown in human bile under aerobic or anaerobic conditions to the early stationary phase and assayed for beta-glucuronidase activity by using rho-nitrophenyl beta-D glucuronide as substrate. Results were normalized and reported as units of enzyme activity per milligram protein of the bacteria. RESULTS: C. perfringens produced beta-glucuronidase enzyme activity that was 34-fold higher than that for E coli, Staphylococcus, Corynebacterium sp., Bacillus sp., Enterococcus sp., Acinetobacter sp., Streptococcus sp., and Klebsiella sp. CONCLUSION: C. perfringens with its higher enzyme activity is more important in the deconjugation of bilirubin diglucuronide than E coli and Klebsiella sp.     

Gallstone ileus: endoscopic removal of a gallstone obstructing the upper jejunum

In a 91-year-old female patient admitted with an ileus, ultrasound and computed tomography demonstrated the obstruction of the upper jejunum by a large gallstone. Due to concurrent diseases the patient was unfit for surgery. An attempt was made to remove the impacted stone endoscopically. After successful mobilization and fragmentation by mechanical lithotripsy the obstruction was cleared away. Since the patient improved considerably after this procedure, the gallbladder and the cholecystoduodenal fistula were left in place.