Serum unconjugated bile acids in patients with small bowel bacterial overgrowth

Concentrations of total and unconjugated bile acids in serum were measured fasting and 2 h postprandially in 9 patients with a positive [14C]glycocholate breath test consistent with small bowel bacterial overgrowth and in 13 controls. Gas-liquid chromatography-mass spectrometry (GLC-MS) and enzymatic-fluorometric assays were both used. In contrast to previous work, total serum bile acids were only occasionally elevated in patients with bacterial overgrowth. Total 2 h postprandial unconjugated bile acids, however, were elevated in 7/9 patients when measured by GLC-MS and in 6/9 when measured by the enzymatic-fluorometric method. The best separation between patients and controls was achieved by GLC-MS determinations of 2 h postprandial unconjugated cholic acid or primary bile acids, which were abnormal in 8/9 patients. This study indicates that measurement of serum bile acids may be a useful approach to the diagnosis of bacterial overgrowth, but would require accessible methods for separating and measuring cholic acid or unconjugated primary bile acids in post-prandial sera.     

Unconjugated serum bile acids as a marker of small intestinal bacterial overgrowth

Non-invasive methods to detect small intestinal bacterial overgrowth often lack specificity in patients who have undergone an ileal resection or have an accelerated intestinal transit. Since elevated serum unconjugated bile acid levels have been found in patients with clinical signs of bacterial overgrowth, we studied the clinical value of unconjugated serum bile acids as a marker of small intestinal bacterial overgrowth. Patients with culture-proven bacterial overgrowth had significantly elevated fasting unconjugated serum bile acid levels (median and range: 4.5; 1.4-21.5 mumol l-1) as compared to healthy subjects (0.9; 0.3-1.7 mumol l-1, P less than 0.005), to persons with an accelerated intestinal transit (1.0; 0.3-1.9 mumol l-1, P less than 0.005) and to persons who have undergone an ileal resection (2.1; 0.7-3.6 mumol l-1, P less than 0.005). The same was true 30 and 60 min after ingestion of a Lundh meal. Serum unconjugated bile acid levels above 4 mumol l-1 were found in eight of 10 patients with culture-proven small intestinal bacterial overgrowth whereas serum levels above 4 mumol l-1 were found in none of the patients from the three control groups. These results suggest that determination of unconjugated serum bile acids is of clinical value in the evaluation of patients suspected of small intestine bacterial overgrowth.     

Fecal excretion of bile acids: a new technique for studying bile acid kinetics in patients with ileal resection

The fecal elimination and enterohepatic circulation of bile acid was studied in 11 patients. 10 patients with varying degrees of ileal disease or resection and 1 patient with pancreatic insufficiency and no ileal disease. A new technique was employed which involved the nearly simultaneous administration of cholic acid-¹⁴C and a nonabsorbable marker. ⁵¹CrCl₃. Each individual stool specimen was collected for 36-96 hr and analyzed separately. Assay of the radioactivity of each isotope allowed the accurate determination of an excretion rate for both cholic acid and ⁵¹Cr. The difference between these rates was used to calculate an absorption coefficient for cholic acid. In addition, bile acid concentration measured by the steroid dehydrogenase technique, and the water content of each stool was determined.     

Biological and medical aspects of active ileal transport of bile acids

The active transport of conjugated bile acids by the ileum is responsible for the enterohepatic circulation of bile acids, a physiological process that ensures an ample supply to the intestine of these key biological surfactants, irrespective of the rate of their biosynthesis from cholesterol. The ileal bile acid transport system is a high capacity, low affinity secondary active Na+ co-transport system that differs in substrate specificity from that present in the hepatocyte. Ileal transport is homeostatically regulated by feedback inhibition of the bile acids that are transported. The enterohepatic circulation is responsible for the concentration profile present in the intestine--high concentrations in the small intestine and low concentrations in the large intestine. Loss of ileal absorption, when mild, leads to a sequence of events that result in increased concentrations in the large intestine causing diarrhea. Severe bile acid malabsorption causes decreased concentrations in the small intestine which in turn lead to fat maldigestion and fat malabsorption. The increased passage of fatty acids into the colon contributes to diarrhea. Fat maldigestion and malabsorption also causes increased absorption of dietary oxalate from the colon which causes hyperoxaluria and contributes to nephrolithiasis. In cholestatic liver disease, inappropriate upregulation of ileal bile acid transport is likely to cause retention of hepatotoxic endogenous bile acids. In familial hypercholesterolemia, efficient bile acid absorption contributes to downregulation of LDL receptors and the maintenance of elevated plasma cholesterol levels; upregulation of bile acid transport during bile acid sequestrant therapy could diminish its efficacy. Efforts are in progress to develop a suitable bile acid analogue to be administered orally for conditions of bile acid deficiency in the small intestine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analysis of conjugated and unconjugated bile acids in serum and jejunal fluid of normal subjects

A reliable method is described for the determination of conjugated and unconjugated bile acids in serum and jejunal fluid. Bile acids are extracted using reverse-phase octadecylsilane bonded silica cartridges and are separated into their unconjugated and conjugated fractions using the lipophilic anion exchanger diethylaminohydroxypropyl Sephadex LH-20 (DEAP-LH-20). The conjugated fraction can be separated into a glycine and a taurine fraction, using the same anion exchanger. The bile acids are measured using a hydroxysteroid dehydrogenase-fluorimetric assay for serum and a hydroxysteroid dehydrogenase-photometric assay for jejunal fluid. The normal fasting serum value of total 3 alpha-hydroxy bile acids amounts to 3.5 +/- 2.8 mumol/l (mean +/- SD, range 1.4-10.8, n = 22). The corresponding unconjugated bile acid fraction amounts to 39.9 +/- 11.2% (range 20.7-64.6%) of total bile acids. The concentration of conjugated bile acids became significantly elevated 30, and 60 min after a standard meal, whereas that of unconjugated bile acids remained unchanged. In jejunal fluid only conjugated bile acids are found, as well in fasting subjects as postprandial, 30 or 60 min after a standard meal.     

Glucuronides of unconjugated 6-hydroxylated bile acids in urine of a patient with malabsorption

The excretion of bile acids in urine from a patient with chronic malabsorption was investigated. Bile acids were separated according to mode of conjugation using a lipophilic anion exchanger, diethylaminohydroxypropyl Sephadex LH-20. Following hydrolysis, individual bile acids were analyzed by computerized GC/MS. In addition, bile acid glucuronides were isolated and their methyl ester trimethylsilyl ether derivatives were directly analyzed by GC/MS. The patient had a normal or slightly increased excretion of bile acids in urine. Bile acids carrying a hydroxyl group at C-6 constituted about 40% of the total. Tetrahydroxylated bile acids were present which have not been found in healthy subjects. Glucuronides of otherwise unconjugated bile acids accounted for 20% of the total. About 90% of these conjugates were 6-hydroxylated, hyodeoxycholic acid being the major bile acid. It is suggested that a specific abnormality of bile acid metabolism is related to the disease in this patient.     

Serum concentrations and excretion of bile acids in cirrhosis.

Bile acid concentrations in serum, and urinary and faecal excretion of bile acids have been studied in ten patients with liver cirrhosis as a consequence of alcohol abuse. Eight of the patients were categorized as Child group A, whereas the remaining two patients comprised Child group C. Individual bile acids were isolated and identified by gas chromatography coupled to mass spectrometry. Total fasting serum bile acid concentrations were elevated in all patients, but not correlated to conventional tests of liver function. Eight of the patients had increased urinary excretion of bile acids. Faecal bile acid-excretion was highly variable between patients, and also between Child's group A and C patients. Total fasting serum bile acid concentrations were not correlated to either urinary, faecal, or total bile acid excretion (= synthesis of bile acids) or to the ratio between urinary and faecal excretion of bile acids. The daily synthesis of bile acids showed a large overlap between Child's group A and C patients. The percentage of chenodeoxycholic acid and its metabolites relative to total daily excretion of bile acids did not correlate, indicating that the synthesis pathways for the primary bile acids does not systematically change in relation to the rate of synthesis. We conclude that even in mild cirrhosis, serum bile acid concentrations are elevated. However, no consistent changes in synthesis of bile acids or synthesis pathways was observed in such patients.     

Faecal bile acid analysis and intestinal absorption in Crohn''s disease before and after ileal resection

Abstract. Faecal bile acids were analysed by gas chromatography in 104 patients. Total bile acids exceeded 1.5 mmol/24 h in 33% of forty-five unoperated patients and in 90% of those having undergone an ileal resection. Lithocholic and deoxycholic fractions were lower in the unoperated patients than in the control group ( P < 0.05 and P < 0.005) and much lower after ileal resection than in unoperated patients ( P < 0.001). A significant correlation ( r = 0.58; P < 0.001) was found between total bile acids and relative proportions of primary bile acids in operated patients, untreated by antibiotics or sulfasalazine. Dihydroxy bile acids (predominantly chenodeoxycholic acid) correlated with faecal weight in unoperated patients ( r = 0.47, P < 0.01) and in 0–50 cm ( r = 0.69, P < 0.001) and 50–100 cm ( r = 0–63, P < 0.01) ileal resection groups. Our results suggest that the frequently altered bile acid composition is related to a shortening of colonic transit time which reduces the exposure of primary bile acids to bacterial 7α-dehydroxylase.     

Identification and quantitative determination of urinary bile acids excreted in cholestasis

The monohydroxy bile acids, 3β-hydroxy-5-cholenoic acid and lithocholic acid and the dihydroxy bile acid, ursodeoxycholic acid have been identified by means of combined gas chromatography-mass spectrometry in urine of patients suffering from acute hepatitis, obstructive jaundice and intermittent jaundice, due to cholelithiasis. The occurrence of these bile acids in obstructive jaundice is suggested to be due to primary hepatic synthesis, since deoxycholic acid, the most sensitive indicator for the enterobacterial metabolism of bile acids, failed to be detected in significant quantities in the urine of these patients. The decrease of the content of deoxycholic acid in the urinary bile acid fraction seems to be of diagnostic value in recognition of complete obstruction. The total daily excretion of bile acids with the urine correlates with the degree of cholestasis, as could be judged from comparisons with serum bilirubin values. The occurrence of 3β-hydroxy-5-cholenoic acid seems to reflect an altered sterol metabolism in cholestasis.     

Serum bile acids after a test meal in Crohn's disease

The serum levels of conjugated cholic and chenodeoxycholic acid have been studied before and during a 4 h period after the intake of a liquid test meal in seven control subjects and in fourteen patients with Crohn's disease. The concentrations of serum bile acids were determined by radioimmunoassay. The control group showed a postprandial increase of both conjugates with a return to the fasting level for cholic acid within 4 h. The chenodeoxycholic acid conjugate did not return to the fasting level within the test period. The serum bile acid concentration in Crohn's disease divided the patients in two groups; one group with decreased or normal fasting levels and low postprandial increase and another group with elevated fasting levels and a postprandial increase without return to the fasting levels within the test period.     

溃疡性结肠炎患者全结直肠切除+回肠贮袋肛管吻合术 术后自我关注的质性研究

目的：了解与探讨溃疡性结肠炎（ulcerative colitis，UC）患者全结直肠切除+回肠贮袋肛管吻合（ileal pouch anal anastomosis，IPAA）术后患者自我关注情况。方法：采用目的抽样法，选取14例UC 行IPAA术后患者，行半结构式深入访谈并采用Colaizzi 7步分析法分析访谈资料。结果：患者多因为自身对术后恢复的期望或疾病相关知识的不足引起对术后排便、饮食、贮袋状态等方面的自我关注。结论：医护人员应注重患者术后自我关注情况，采取相应的心理疏导措施，在饮食、贮袋状态等方面给予患者更加专业细致的指导和教育，加强出院后延续护理，以提高患者术后生活质量，促进疾病康复。     

Diet and intestinal bacterial overgrowth: Is there evidence?

The intestinal microbiota and its role in health and disease processes have been the subject of several studies. It is known that changes in the intestinal microbiota occur due to several factors, such as the use of medication, age, lifestyle and diseases, which can modify intestinal homeostasis and lead to excessive growth of bacteria in the small intestine, triggering a clinical condition called small bowel bacterial overgrowth (SIBO). Individuals with SIBO may present gastrointestinal symptoms ranging from nausea, diarrhea and/or constipation, and flatulence to distension and abdominal pain, resulting from poor absorption of nutrients or changes in intestinal permeability. The gold-standard treatment is based on the use of antibiotics to eradicate bacterial overgrowth. Some studies have evaluated diets in the treatment of SIBO; however, the studies are of low methodological quality, making extrapolation of the results to clinical practice unfeasible. Thus, there is still not enough scientific evidence to support a specific type of diet for the treatment of SIBO.