Serum Deoxycholic Acid Research Articles

Predictive value of bile acids as metabolite biomarkers for gallstone disease: A systematic review and meta-analysis.

The profiles of bile acids (BAs) in patients with gallstone disease (GSD) have been found to be altered markedly though in an inconsistent pattern. This study aims to characterize the variation of the BA profiles in GSD patients, thereby to discover the potential metabolite biomarkers for earlier detection of GSD. Literature search of eight electronic database in both English and Chinese was completed on May 11, 2023. The qualitative and quantitative reviews were performed to summarize the changes of BA profiles in GSD patients compared with healthy subjects. The concentrations of BAs were adopted as the primary outcomes and the weighted mean differences (WMDs) and 95% confidence interval (CI) were generated by random-effects meta-analysis models. A total of 30 studies were enrolled which included 2313 participants and reported the 39 BAs or their ratios. Qualitative review demonstrated serum Taurocholic Acid (TCA), Glycochenodeoxycholic acid (GCDCA), Glycocholic acid (GCA), Taurochenodeoxycholic acid (TCDCA), Glycodeoxycholic acid (GDCA) and Deoxycholic acid (DCA) were significantly increased in GSD patients compared with healthy subjects. Meta analysis was performed in 16 studies and showed that serum Total BAs (TBA) (WMD = 1.36μmol/L, 95%CI = 0.33; 2.4) was elevated however bile TBA (WMD = -36.96mmol/L, 95%CI = -52.32; -21.6) was declined in GSD patients. GCA (WMD = 0.83μmol/L, 95%CI = 0.06; 1.6) and TCA (WMD = 0.51μmol/L; 95%CI = 0.18; 0.85) were both increased in serum sample; TCDCA (WMD = 2.64mmol/L, 95%CI = 0.16; 5.12) was rising, however GCDCA (WMD = -13.82mmol/L, 95%CI = -21.86; -5.78) was falling in bile sample of GSD patients. The level of serum DCA in the GSD patients was found to be increased by using chromatography, yet decreased by chromatography mass spectrometry. The profiles of BAs demonstrated distinctive changes in GSD patients compared with healthy control subjects. Serum GCA, TCA and GCDCA, as the typically variant BAs, presented as a potential marker for earlier diagnosis of GSD, which could facilitate early prophylactic intervention. Yet, further validation of these biomarkers by longitudinal studies is still warranted in the future. PROSPERO registration number CRD42022339649.

Evaluation of gut dysbiosis using serum and fecal bile acid profiles.

Dysbiosis in the intestinal microflora can affect the gut production of microbial metabolites, and toxic substances can disrupt the barrier function of the intestinal wall, leading to the development of various diseases. Decreased levels of Clostridium subcluster XIVa (XIVa) are associated with the intestinal dysbiosis found in inflammatory bowel disease (IBD) and Clostridium difficile infection (CDI). Since XIVa is a bacterial group responsible for the conversion of primary bile acids (BAs) to secondary BAs, the proportion of intestinal XIVa can be predicted by determining the ratio of deoxycholic acid (DCA)/[DCA + cholic acid (CA)] in feces orserum. For example, serum DCA/(DCA+CA) was significantly lower in IBD patients than in healthy controls, even in the remission period. These results suggest that a low proportion of intestinal XIVa in IBD patients might be a precondition for IBD onset but not a consequence of intestinal inflammation. Another report showed that a reduced serum DCA/(DCA + CA) ratio could predict susceptibility to CDI. Thus, the BA profile, particularly the ratio of secondary to primary BAs, can serve as a surrogate marker of the intestinal dysbiosis caused by decreased XIVa.

Secondary bile acids mediate high-fat diet-induced upregulation of R-spondin 3 and intestinal epithelial proliferation.

A high-fat diet (HFD) contributes to the increased incidence of colorectal cancer, but the mechanisms are unclear. We found that R-spondin 3 (Rspo3), a ligand for leucine-rich, repeat-containing GPCR 4 and 5 (LGR4 and LGR5), was the main subtype of R-spondins and was produced by myofibroblasts beneath the crypts in the intestine. HFD upregulated colonic Rspo3, LGR4, LGR5, and β-catenin gene expression in specific pathogen-free rodents, but not in germ-free mice, and the upregulations were prevented by the bile acid (BA) binder cholestyramine or antibiotic treatment, indicating mediation by both BA and gut microbiota. Cholestyramine or antibiotic treatments prevented HFD-induced enrichment of members of the Lachnospiraceae and Rumincoccaceae, which can transform primary BA into secondary BA. Oral administration of deoxycholic acid (DCA), or inoculation of a combination of the BA deconjugator Lactobacillus plantarum and 7α-dehydroxylase-containing Clostridium scindens with an HFD to germ-free mice increased serum DCA and colonic Rspo3 mRNA levels, indicating that formation of secondary BA by gut microbiota is responsible for HFD-induced upregulation of Rspo3. In primary myofibroblasts, DCA increased Rspo3 mRNA via TGR5. Finally, we showed that cholestyramine or conditional deletion of Rspo3 prevented HFD- or DCA-induced intestinal proliferation. We conclude that secondary BA is responsible for HFD-induced upregulation of Rspo3, which, in turn, mediates HFD-induced intestinal epithelial proliferation.

Hepatocellular cystathionine γ lyase/hydrogen sulfide attenuates nonalcoholic fatty liver disease by activating farnesoid X receptor.

Hydrogen sulfide (H2 S) plays a protective role in NAFLD. However, whether cystathionine γ lyase (CSE), a dominant H2 S generating enzyme in hepatocytes, has a role in the pathogenesis of NAFLD is currently unclear. We showed that CSE protein expression is dramatically downregulated, especially in fibrotic areas, in livers from patients with NAFLD. In high-fat diet (HFD)-induced NAFLD mice or an oleic acid-induced hepatocyte model, the CSE/H2 S pathway is also downregulated. To illustrate a regulatory role for CSE in NAFLD, we generated a hepatocyte-specific CSE knockout mouse (CSELKO ). Feeding an HFD to CSELKO mice, they showed more hepatic lipid deposition with increased activity of the fatty acid de novo synthesis pathway, increased hepatic insulin resistance, and higher hepatic gluconeogenic ability compared to CSELoxp control mice. By contrast, H2 S donor treatment attenuated these phenotypes. Furthermore, the protection conferred by H2 S was blocked by farnesoid X receptor (FXR) knockdown. Consistently, serum deoxycholic acid and lithocholic acid (FXR antagonists) were increased, and tauro-β-muricholic acid (FXR activation elevated) was reduced in CSELKO . CSE/H2 S promoted a post-translation modification (sulfhydration) of FXR at Cys138/141 sites, thereby enhancing its activity to modulate expression of target genes related to lipid and glucose metabolism, inflammation, and fibrosis. Sulfhydration proteomics in patients' livers supported the CSE/H2 S modulation noted in the CSELKO mice. FXR sulfhydration is a post-translational modification affected by hepatic endogenous CSE/H2 S that may promote FXR activity and attenuate NAFLD. Hepatic CSE deficiency promotes development of nonalcoholic steatohepatitis. The interaction between H2 S and FXR may be amenable to therapeutic drug treatment in NAFLD.

Evaluation of the Risk of Clostridium difficile Infection Using a Serum Bile Acid Profile.

Since intestinal secondary bile acids (BAs) prevent Clostridium difficile infection (CDI), the serum BA profile may be a convenient biomarker for CDI susceptibility in human subjects. To verify this hypothesis, we investigated blood samples from 71 patients of the Division of Gastroenterology and Hepatology at the time of admission (prior to antibiotic use and CDI onset). Twelve patients developed CDI during hospitalization, and the other 59 patients did not. The serum unconjugated deoxycholic acid (DCA)/[DCA + unconjugated cholic acid (CA)] ratio on admission was significantly lower in patients who developed CDI than in patients who did not develop CDI (p < 0.01) and in 46 healthy controls (p < 0.0001). Another unconjugated secondary BA ratio, 3β-hydroxy (3βOH)-BAs/(3βOH + 3αOH-BAs), was also significantly lower in patients who developed CDI than in healthy controls (p < 0.05) but was not significantly different between patients who developed and patients who did not develop CDI. A receiver operating characteristic (ROC) curve determined a cut-off point of DCA/(DCA + CA) < 0.349 that optimally discriminated on admission the high-risk patients who would develop CDI (sensitivity 91.7% and specificity 64.4%). In conclusion, a decreased serum DCA/(DCA + CA) ratio on admission strongly correlated with CDI onset during hospitalization in patients with gastrointestinal and hepatobiliary diseases. Serum BA composition could be a helpful biomarker for predicting susceptibility to CDI.

Detection of Gut Dysbiosis due to Reduced Clostridium Subcluster XIVa Using the Fecal or Serum Bile Acid Profile.

Dysbiosis, especially a reduced Clostridium subcluster XIVa (XIVa), has been reported in several gastrointestinal diseases. Since XIVa is thought to be the main bacterial cluster that metabolizes bile acids (BAs) in the human intestine, we hypothesized that the BA profile in feces, and possibly in serum, could be a convenient biomarker for intestinal XIVa activity. First, blood and feces were collected from 26 healthy controls and 20 patients with gastrointestinal diseases, and the relationships among fecal microbiomes and fecal and serum BA compositions were studied. Second, serum BA compositions of 30 healthy controls and the remission and exacerbation states of 14 Crohn's disease (CD) and 12 ulcerative colitis (UC) patients were compared. Fecal microbiomes were analyzed by terminal restriction fragment length polymorphism analysis, and BA compositions were quantified by HPLC-MS/MS. The highest positive correlation was observed between the fecal XIVa proportion and fecal unconjugated deoxycholic acid (DCA)/(DCA+unconjugated cholic acid [CA]) (r = 0.77, P < 0.0001) or serum DCA/(DCA+CA) (r = 0.52, P < 0.001). Diurnal variation in serum XIVa candidate markers also showed that DCA/(DCA+CA) was most stable and not affected by the contraction of the gallbladder. Serum DCA/(DCA+CA) was not significantly different between remission and exacerbation states in either CD or UC patients, but was significantly reduced in those in the remission state of CD and the remission and exacerbation states of UC compared with healthy controls (P < 0.05). Decreased XIVa exhibits a strong correlation with reduced intestinal BA metabolism. Fecal and serum DCA/(DCA+CA) could be useful surrogate markers for the intestinal proportion of XIVa.

The membrane bile acid receptor TGR5 drives cell growth and migration via activation of the JAK2/STAT3 signaling pathway in non-small cell lung cancer

Mounting evidence suggests that an emerging G protein-coupled receptor, TGR5, plays a crucial role ranging from metabolic diseases to cancers. However, the biological functions of TGR5 in non-small cell lung cancer (NSCLC) remain elusive. We found that TGR5 was aberrantly expressed in NSCLC and positively correlated with an advanced clinical stage in NSCLC patients. We further discovered that TGR5 knockdown prevented JAK2 and STAT3 phosphorylation and repressed the expression of STAT3 target genes, thus inhibiting cell proliferation, migration and invasion in NSCLC. Moreover, the promotive effects of TGR5 were significantly reversed by a JAK2 inhibitor or STAT3 knockdown. Additionally, we demonstrated a positive correlation between TGR5 and p-STAT3 expression in NSCLC tissue samples. Patients with both high TGR5 and p-STAT3 expression had the worst prognosis. In addition, the serum levels of deoxycholic acid (DCA), ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) in NSCLC patients were much higher than those in the healthy controls and the patients with higher serum DCA levels had stronger TGR5 expression simultaneously. Moreover, DCA markedly promoted NSCLC cell migration and invasion through a TGR5-dependent way. Taken together, these results indicate that TGR5 drives cell growth and migration through JAK2/STAT3 signaling pathway in NSCLC.

Deoxycholic Acid, a Metabolite of Circulating Bile Acids, and Coronary Artery Vascular Calcification in CKD

Vascular calcification is common among patients with chronic kidney disease (CKD),and it is associated with all-cause and cardiovascular disease mortality. Deoxycholic acid, a metabolite of circulating bile acids, is elevated in CKD and induces vascular mineralization and osteogenic differentiation in animal models. Cohort analysis of clinical trial participants. 112 patients with moderate to severe CKD (estimated glomerular filtration rate, 20-45mL/min/1.73m2) who participated in a randomized controlled study to examine the effects of phosphate binders on vascular calcification. Serum deoxycholic acid concentration. Baseline coronary artery calcification (CAC) volume score and bone mineral density (BMD) and change in CAC volume score and BMD after 9 months. Deoxycholic acid was assayed in stored baseline serum samples using liquid chromatography-tandem mass spectrometry, CAC was measured using a GE-Imitron C150 scanner, and BMD was determined using computed tomographic scans of the abdomen with calibrated phantom of known density. Higher serum deoxycholic acid concentrations were significantly correlated with greater baseline CAC volume and lower baseline BMD. After adjusting for demographics, coexisting illness, body mass index, estimated glomerular filtration rate, and concentrations of circulating markers of mineral metabolism, including serum calcium, phosphorus, vitamin D, parathyroid hormone, and fibroblast growth factor 23, a serum deoxycholic acid concentration > 58ng/mL (the median) was positively associated with baseline CAC volume (β=0.71; 95% CI, 0.26-1.16; P=0.003) and negatively associated with baseline BMD (β=-20.3; 95% CI,-1.5 to-39.1; P=0.04). Serum deoxycholic acid concentration > 58ng/mL was not significantly associated with change in CAC volume score after 9 months (β=0.06; 95% CI,-0.09 to 0.21; P=0.4). The analysis for the relationship between baseline deoxycholic acid concentrations and change in BMD after 9 months was not statistically significant, but was underpowered. The use of nonfasting serum samples is a limitation because deoxycholic acid concentrations may vary based on time of day and dietary intake. Few trial participants with complete data to evaluate the change in CAC volume score (n=75) and BMD (n=59). No data for changes in deoxycholic acid concentrations over time. Among patients with moderate to severe CKD, higher serum deoxycholic acid concentrations were independently associated with greater baseline CAC volume score and lower baseline BMD.

Organic anion-transporting polypeptide 1a4 (Oatp1a4) is important for secondary bile acid metabolism

Organic anion transporting polypeptides (human: OATPs; rodent: Oatps) were thought to have important functions in bile acid (BA) transport. Oatp1a1, 1a4, and 1b2 are the three major Oatp1 family members in rodent liver. Our previous studies have characterized the BA homeostasis in Oatp1a1-null and Oatp1b2-null mice. The present study investigated the physiological role of Oatp1a4 in BA homeostasis by using Oatp1a4-null mice. Oatp1a4 expression is female-predominant in livers of mice, and thereby it was expected that female Oatp1a4-null mice will have more prominent changes than males. Interestingly, the present study demonstrated that female Oatp1a4-null mice had no significant alterations in BA concentrations in serum or liver, though they had increased mRNA of hepatic BA efflux transporters (Mrp4 and Ostα/β) and ileal BA transporters (Asbt and Ostα/β). In contrast, male Oatp1a4-null mice showed significantly altered BA homeostasis, including increased concentrations of deoxycholic acid (DCA) in serum, liver and intestinal contents. After feeding a DCA-supplemented diet, male but not female Oatp1a4-null mice had higher concentrations of DCA in serum and livers than their WT controls. This suggested that Oatp1a4 is important for intestinal absorption of secondary BAs in male mice. Furthermore, loss of Oatp1a4 function did not decrease BA accumulation in serum or livers of bile-duct-ligated mice, suggesting that Oatp1a4 is not likely a BA uptake transporter. In summary, the present study for the first time demonstrates that Oatp1a4 does not appear to mediate the hepatic uptake of BAs, but plays an important male-predominant role in secondary BA metabolism in mice.

Serum bile acids, programmed cell death and cell proliferation in the mucosa of patients with colorectal adenomas

Background. Deoxycholic acid induced programmed cell death and an imbalance with cell proliferation may favour colorectal tumourigenesis according to ‘in vitro’ studies, but information is lacking on the relationships occurring ‘in vivo’ in humans. Aims. To evaluate whether serum deoxycholic acid is associated with programmed cell death and cell proliferation in colonic mucosa. Methods. In 10 patients with colorectal adenomas, we measured fasting serum levels of bile acids; and, in normal colonic mucosa, programmed cell death by the TUNEL technique and cell proliferation by immunohistochemical staining with anti-Ki67. Total and compartmental indices for both activities were calculated. Results. Among serum bile acids, only total deoxycholic acid (median: 0.89 μmol/L ±0.54 95% CI), showed a significant positive correlation with the total and basal compartments PCD Index ( r = 0.68, p < 0.05). Total proliferation index showed no correlation with either total PCD Index, or bile acids. Within the median compartment of the crypt, cell proliferation was negatively associated with all unconjugated bile acids. Conclusions. The positive association between deoxycholic acid and programmed cell death in the basal compartment of the crypt, and the negative association of cell proliferation and unconjugated bile acids in the median compartment, do not seem to support the co-carcinogenic effect of deoxycholic acid.

Does Ursodeoxycholic Acid Change the Proliferation of the Colorectal Mucosa?

Background: In animal models ursodeoxycholic acid (UDCA) showed a chemoprotective effect against colon cancer. To explain this, a reduced proliferation of the colorectal mucosal proliferation was suggested. We, therefore, examined the influence of UDCA on the proliferation of normal colorectal mucosa in humans. Methods: Following endoscopic polypectomy, 20 patients with colorectal adenomas were randomized to receive either UDCA (750 mg/day, n = 10, group A) or placebo (n = 10, group B) for 6 months in a double-blinded way. Colorectal biopsies were sampled before and at the end of the medication by total colonoscopy. Colorectal mucosal proliferation was measured by FACScan analysis of propidium iodine labeling. Serum was sampled, and serum bile acids were analyzed by gas chromatography. Results: The proliferation rates at the end of the study were similar in both groups (median 15.4%; range 12.0–20.9 in group A; median 16.0%, 14.0–20.2 in group B, p = 0.41). Serum lithocholic acid levels at the end of the study were significantly higher in group A (1.3 µmol/l, 0.9–1.8) than in group B (0.7 µmol/l, 0–1.7, p < 0.02), whereas serum deoxycholic acid levels were similar in both groups. Conclusions: In this study, UDCA treatment for 6 months does not seem to induce changes in the proliferative behavior of the colorectal mucosa in patients with adenomas. It seems likely that a putative chemopreventive effect of UDCA in humans is not exerted by a reduction of the colorectal proliferation.

Effects of cisapride on gall bladder emptying, intestinal transit, and serum deoxycholate: a prospective, randomised, double blind, placebo controlled trial

BACKGROUNDOctreotide inhibits gall bladder emptying and prolongs intestinal transit. This leads to increases in the proportion of deoxycholic acid in, and cholesterol saturation of, gall bladder bile, factors that contribute...

Influence of pH on the phase distribution of nascent deoxycholic acid in fresh human cecal aspirates.

Prolonged large bowel transit time and an associated increase in the proportion of deoxycholic acid (DCA) in serum and bile have been implicated in the development of cholesterol-rich gallstones and colon cancer. Prolongation of intestinal transit also increases intracolonic pH that, we hypothesized, should favor the solubilization and absorption of newly formed DCA within the colon. To test this hypothesis, we performed in vitro studies on homogenized cecal aspirates (obtained at colonoscopy) that were incubated anaerobically with [14C]cholic acid for 16 h after which the pH was adjusted to between 4.0 and 7.0 in 0.5-pH unit steps. The resultant reaction mixtures were centrifuged to separate the supernatant from the precipitate, and the specific activity of [14C]DCA was quantitated in both phases. As the pH in the aspirates was manipulated from 4.0 to 7.0, the proportion of newly formed, labeled DCA increased in the supernatant and fell in the precipitate, particularly at a hydrogen ion concentration of <100 x 10(-7) (equivalent to pH 5.0-7.0). These results show that the solubility of DCA in colonic contents increases with increasing pH. If solubility is rate limiting, this should lead to increased absorption that, in turn, would explain why the proportion of DCA in serum and bile increases with the prolongation of large bowel transit time.

Mechanism for the transit-induced increase in colonic deoxycholic acid formation in cholesterol cholelithiasis

Background & Aims: Many patients with cholesterol gallbladder stones (GBS) have a high percentage of deoxycholic acid (DCA) in gallbladder bile (all of which are in the conjugated form), probably as a result of prolonged large bowel transit times (LBTT). However, whether the prolonged LBTT increases DCA formation, solubilization, or absorption (or all 3) is not known. Methods: In 40 subjects (20 with GBS; age range, 24–74 years), we measured LBTT using radiopaque markers, and intestinal luminal pH by radiotelemetry. We also measured quantitative anaerobic bacteriology and the activities of 2 bile acid–metabolizing enzymes in fresh cecal aspirates obtained during clinically indicated unprepared colonoscopy, and related these results to the percentage of DCA in fasting serum measured by gas chromatography–mass spectrometry. Results: Compared with controls, GBS patients had longer LBTT (mean 23.1 ± SEM 2.8 h vs. 36.5 ± 3.3 h; P < 0.01); more total (2.7 ± 0.6 × 109 vs. 5.9 ± 1.5 × 109 cfu/mL) and Gram-positive (9.5 ± 3.1 × 108 vs. 18.0 ± 4.1 × 108 cfu/mL; P < 0.05) anaerobes; and greater 7α-dehydroxylating (7α-DH) activity (3.39 ± 0.59 vs. 10.37 ± 1.15 × 10−4 U/mg protein) in the cecal aspirates. They also had higher intracolonic pH values (P < 0.02) and increased percentages of DCA in fasting serum (13.4% ± 1.52% vs. 21.8% ± 2.19%; P < 0.005). Results of univariate and multivariate analyses confirmed that LBTT was critical in determining the percentage of DCA in serum and showed that 7α-DH activity and apparent distal colonic pH were also significant independent variables. Conclusions: Slow colonic transit (more time), increased Gram-positive anaerobes (more bacteria), and greater 7α-DH activity (more enzyme) favor enhanced DCA formation; transit-induced increases in distal colonic luminal pH favor enhanced DCA solubilization/bioavailability; and increases in LBTT (more time) again favor DCA absorption.GASTROENTEROLOGY 2000;119:806-815

Review: pathogenesis of gallstones.

The aim of this article is to review selected aspects of the pathogenesis of cholesterol-rich, gall-bladder stones (GBS)--with emphasis on recent developments in biliary cholesterol saturation, cholesterol microcrystal nucleation, statis within the gall-bladder and, particularly, on the roles of intestinal transit and altered deoxycholic acid (DCA) metabolism, in GBS development. In biliary cholesterol secretion, transport and saturation, recent developments include evidence in humans and animals, that bile lipid secretion is under genetic control. Thus in mice the md-2 gene, and in humans the MDR-3 gene, encodes for a canalicular protein that acts as a 'flippase' transporting phospholipids from the inner to the outer hemi-leaflet of the canalicular membrane. In the absence of this gene, there is virtually no phospholipid or cholesterol secretion into bile. Furthermore, when inbred strains of mice that have 'lith genes' are fed a lithogenic diet, they become susceptible to high rates of GBS formation. The precipitation/nucleation of cholesterol microcrystals from supersaturated bile remains a critical step in gallstone formation. methods of studying this phenomenon have now been refined from the original 'nucleation time' to measurement of cholesterol appearance/detection times, and crystal growth assays. Furthermore, the results of recent studies indicate that, in addition to classical Rhomboid-shape monohydrate crystals, cholesterol can also crystallize, transiently, as needle-, spiral- and tubule-shaped crystals of anhydrous cholesterol. A lengthy list of promoters, and a shorter list of inhibitors, has now been defined. There are many situations where GB stasis in humans is associated with an increased risk of gallstone formation--including iatrogenic stone formation in acromegalic patients treated chronically with octreotide (OT). As well as GB stasis, however, OT-treated patients all have 'bad' bile which is supersaturated with cholesterol, has excess cholesterol in vesicles, rapid microcrystal mulceation times and a two-fold increase in the percentage DCA in bile. This increase in the proportion of DCA seems to be due to OT-induced prolongation of large bowel transit time (LBTT). Thus LBTT is linearly related to (i) the percentage of DCA in serum; (ii) the DCA pool size; and (III) the DCA input or 'synthesis' rate. Furthermore, the intestinal prokinetic, cisapride, counters the adverse effects of OT on intestinal transit, and 'normalizes' the percentage of DCA in serum/bile. Patients with spontaneous gallstone disease also have prolonged LBTTs, more colonic gram-positive anaerobes, increased bile acid metabolizing enzymes and higher intracolonic pH values, than stone-free controls. Together, these changes lead to increased DCA formation, solubilization and absorption, Thus, in addition to the 'lithogenic liver' and 'guilty gall-bladder' one must now add the 'indolent intestine' to the list of culprits in cholesterol gallstone formation.

Transit induced changes in serum deoxycholic acid stimulate increased mitoses within colonic crypts: Controls vs patients with adenomatous polyps

Transit induced changes in serum deoxycholic acid stimulate increased mitoses within colonic crypts: Controls vs patients with adenomatous polyps

Prolonged large bowel transit increases serum deoxycholic acid: a risk factor for octreotide induced gallstones

BACKGROUNDTreatment of acromegaly with octreotide increases the proportion of deoxycholic acid in, and the cholesterol saturation of, bile and induces the formation of gallstones. Prolongation of intestinal transit has been...

Colonic mucosal proliferation is related to serum deoxycholic acid levels

Hyperproliferation of the colorectal mucosa is regarded as an early step in colorectal carcinogenesis. Deoxycholic acid, a secondary bile acid, stimulates colorectal epithelial proliferation in animals and is considered a tumor promoter in human colorectal carcinogenesis. The aim of this study was to investigate the correlation between colorectal mucosal proliferation and the serum deoxycholic acid level. From each of 19 patients (10 men and 9 women) with (n = 3) or without (n = 16) colorectal adenoma, 18 biopsy specimens were obtained by colonoscopy, 3 from each of the 6 colonic segments. A crude nuclei fraction was prepared, and DNA was stained by propidium iodide to determine the proliferative index (the percentage of cells in the S and G2/M phases of the cell cycle) by flow cytometry. Serum levels of deoxycholic acid were determined by gas-liquid chromatography. The colonic proliferation rates (median of the values obtained in all segments, 14.1%; range, 10.0-18.7%) and the fasting serum deoxycholic acid levels (median, 0.86 micromol/L; range, 0.28-1.58 micromol/L) showed a significant correlation (r = 0.51, P = 0.03). Serum lithocholic, cholic, chenodeoxycholic, and ursodeoxycholic acid levels were not correlated with the proliferation rates. Levels of deoxycholic acid in serum are correlated with the rates of the colorectal mucosa. These results are consistent with the concept that deoxycholic acid promotes colorectal carcinogenesis.

Colonic mucosal proliferation is related to serum deoxycholic acid levels

Colonic mucosal proliferation is related to serum deoxycholic acid levels

Bile acids in serum and bile of patients with cholesterol gallstone.

AIM:To analyze serum bile acids and biliary lipids of patients with cholesterol gallstone(CS) and explore the relationship between deoxycholic acid (DCA) and CS disease.METHODS: Analysis of bile acids in serum was done with gas-chromatography in two groups: CS group (n=151) and control group (n=256). Serum bile acids and biliary lipids were also studied in 90 matched samples.RESULTS: The serum DCA was 0.955&mgr;mol/L plus minus 0.078&mgr;mol/L in CS group, which was more than that of control group (0.696&mgr;mol/L plus minus 0.047&mgr;mol/L), P < 0.01. The ratio of DCA/chenodeoxycholic acids (CDCA) was 1.76 plus minus0.30 in CS group, about two times that in control group (0.92 plus minus 0.14). The mole percent of DCA in bile was positively related to cholesterol saturation index (CSI) (P < 0.01) and the mole percent of CDCA in bile negatively to CSI (P = 0.01). There was correlation between the mole percent of DCA, CDCA and cholic acid in bile and in serum.CONCLUSION: It is suggested that DCA is lithogenic and the increased amount of DCA or the ratio of DCA/CDCA in serum may be one of the features of cholesterol gallstone patients.