Serum Total Bile Acids in Relation to Gastrointestinal Cancer Risk: A Retrospective Study.
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ABSTRACT: Background
Bile acids (BAs) have been proposed to promote gastrointestinal cells carcinogenesis. However, studies on serum total bile acid (TBA) levels and gastrointestinal cancers (GICs) risk are rare.Methods
We conducted a retrospective case-control study from 2015 to 2019 at the First Affiliated Hospital of Air Force Military Medical University, in which 4,256 GICs cases and 1,333 controls were recruited. Patients' demographic, clinical and laboratory data were collected. The odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using binary logistic regression models.Results
Positive associations were observed between serum TBA levels and risks of esophageal cancer (EC), gastric cancer (GC) and colorectal cancer (CRC). Overall, ORs of EC, GC and CRC risk rose with the TBA levels increasing. After adjustment for potential confounders, the OR of TBA-positive for EC risk was 4.89 (95% CI: 3.20-7.49), followed by GC (OR: 3.92, 95% CI: 2.53-6.08), and CRC (OR: 3.32, 95% CI: 2.04-5.11). Patients aged 60 years or older have a higher risk of GICs, especially for EC patients. Males are associated with a higher risk of GC, while females are associated with a higher risk of CRC. Preoperative serum TBA positive and negative was significantly different in the presence or absence of hematogenous metastasis among EC patients (P=0.014), and lymph node metastasis among GC patients (P=0.018).Conclusions
This retrospective study showed positive associations between serum TBA level and GICs risk, and a higher serum TBA level constitutes a risk factor for GICs.
SUBMITTER: Li S
PROVIDER: S-EPMC9213662 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC4243585 | biostudies-literature
Project description:ImportanceBile acids play essential roles in metabolic modulation. Excessive serum total bile acid (sTBA) levels during pregnancy are associated with adverse perinatal outcomes; however, their association with the risk of intrauterine growth restriction (IUGR) remains unclear.ObjectiveTo investigate the association between maternal sTBA concentration during pregnancy and the risk of IUGR.Design, setting, and participantsThis retrospective cohort study included pregnant individuals who delivered live singleton neonates and had regular antenatal examination records available at a hospital-based center in Shanghai, China, from 2014 to 2018. Data were analyzed from July to November 2020.ExposuresMaternal sTBA concentration during pregnancy.Main outcomes and measuresFetal birth weight and probability of low birth weight (LBW) and IUGR.ResultsThis study included 68 245 singleton pregnancies with live births for analysis. The mean (SD) age of the pregnant individuals was 30.5 (3.8) years, 67 168 patients (98.4%) were Han, and 50 155 (73.5%) were nulliparous. Nonlinear regression models suggested that there was an inverted J-shaped association between maternal sTBA level during pregnancy and fetal birth weight, with a steep decrease in birth weight at high sTBA levels (estimated mean [SE] birth weight for sTBA of 40.8 ug/mL, 2879 [39.9] g) and greater birth weights at lower sTBA levels (estimated mean [SE] birth weight for sTBA 0.4 μg/mL, 3290 [3.9] g; and for 4.1 μg/mL, 3334 [1.6] g). Lower birth weight and a higher incidence of IUGR were observed in patients with gestational hypercholanemia (sTBA ≥4.08 μg/mL) compared with those without gestational hypercholanemia (birth weight: estimated adjusted mean [SE], 3309 [3.32] vs 3338 [0.80] g; P = .005; incidence of IUGR: 62 of 4467 [1.4%] vs 312 of 63 778 [0.5%]; P < .001). Moreover, compared with patients with sTBA concentrations of less than 4.08 μg/mL, those with gestational hypercholanemia had an increased risk of LBW (adjusted odds ratio [aOR], 1.29; 95% CI, 1.09-1.53) and IUGR (aOR, 2.18; 95% CI, 1.62-2.91). In addition, there was an additive interaction between hypertensive disorders in pregnancy (HDP) and hypercholanemia on LBW and IUGR risk. The highest risks of LBW and IUGR were found in pregnant individuals with both HDP and hypercholanemia compared with those with normotensive pregnancies with sTBA concentrations less than 4.08 μg/mL (LBW: aOR, 9.13; 95% CI, 6.88-12.12; IUGR: aOR, 19.14; 95% CI, 12.09-30.28).Conclusions and relevanceThis study found that gestational hypercholanemia was associated with an increased risk of LBW and IUGR, especially in pregnant individuals with HDP. Therefore, it would be meaningful to monitor sTBA concentration during the follow-up of pregnancies with potential IUGR.
| S-EPMC8290304 | biostudies-literature
Project description:Host-gut microbiota metabolic interactions are closely associated with health and disease. A manifestation of such co-metabolism is the vast structural diversity of bile acids (BAs) involving both oxidative stereochemistry and conjugation. Herein, we describe the development and validation of a LC-MS-based method for the analysis of human C24 BA metabolome in serum and urine. The method has high throughput covering the discrimination of oxidative stereochemistry of unconjugated species in a 15-min analytical cycle. The validated quantitative performance provided an indirect way to ascertain the conjugation patterns of BAs via enzyme-digestion protocols that incorporated the enzymes, sulfatase, β-glucuronidase, and choloylglycine hydrolase. Application of the method has led to the detection of at least 70 unconjugated BAs including 27 known species and 43 newly found species in the post-prandial serum and urine samples from 7 nonalcoholic steatohepatitis patients and 13 healthy volunteers. Newly identified unconjugated BAs included 3α, 12β-dihydroxy-5β-cholan-24-oic acid, 12α-hydroxy-3-oxo-5β-cholan-24-oic acid, and 3α, 7α, 12β-trihydroxy-5β-cholan-24-oic acid. High-definition negative fragment spectra of the other major unknown species were acquired to facilitate future identification endeavors. An extensive conjugation pattern is the major reason for the "invisibility" of the newly found BAs to other common analytical methods. Metabolomic analysis of the total unconjugated BA profile in combination with analysis of their conjugation patterns and urinary excretion tendencies have provided substantial insights into the interconnected roles of host and gut microbiota in maintaining BA homeostasis. It was proposed that the urinary total BA profile may serve as an ideal footprint for the functional status of the host-gut microbial BA co-metabolism. In summary, this work provided a powerful tool for human C24 BA metabolome analysis that bridges the gap between GC-MS techniques in the past age and LC-MS techniques currently prevailing in biomedical researches. Further applications of the present method in clinical, translational research, and other biomedical explorations will continue to boost the construction of a host-gut microbial co-metabolism network of BAs and thus facilitate the decryption of BA-mediated host-gut microbiota crosstalk in health and diseases. Graphical abstract ᅟ.
| S-EPMC6424582 | biostudies-literature
Project description:BackgroundBile acids (BAs) not only play an important role in lipid metabolism and atherosclerosis but also have antiapoptotic and neuroprotective effects. However, few studies have focused on the relationship of the total bile acid (TBA) levels with the severity and prognosis of acute ischemic stroke (AIS).ObjectivesThe aim of this study was to investigate the potential associations of the fasting serum TBA levels on admission with the stroke severity, in-hospital complication incidence and 3 -month all-cause mortality in patients with AIS.MethodsA total of 777 consecutive AIS patients were enrolled in this study and were divided into four groups according to the quartiles of the serum TBA levels on admission. Univariate and multivariate logistic regression analyses were used to explore the relationship between the fasting TBA levels and the stroke severity, in-hospital complications, and 3-month mortality in AIS patients.ResultsPatients in group Q3 had the lowest risk of severe AIS (NIHSS > 10) regardless of the adjustments for confounders (P < 0.05). During hospitalization, 115 patients (14.8%) had stroke progression (NIHSS score increased by ≥ 2), and 222 patients (28.6%) developed at least one complication, with no significant difference among the four groups (P > 0.05). There was no significant difference in the incidence of pneumonia, urinary tract infection (UTI), hemorrhagic transformation (HT), gastrointestinal bleeding (GIB), seizures or renal insufficiency (RI) among the four groups (P > 0.05). A total of 114 patients (14.7%) died from various causes (including in-hospital deaths) at the 3-month follow-up, including 42 (21.3%), 26 (13.3%), 19 (9.9%) and 27 (13.9%) patients in groups Q1, Q2, Q3 and Q4 respectively, with significant differences (P = 0.013). After adjusting for confounding factors, the risk of death decreased (P -trend < 0.05) in groups Q2, Q3, and Q4 when compared with group Q1, and the OR values were 0.36 (0.16-0.80), 0.30 (0.13-0.70), and 0.29 (0.13-0.65), respectively.ConclusionsTBA levels were inversely associated with the 3-month mortality of AIS patients but were not significantly associated with the severity of stroke or the incidence of complications.
| S-EPMC8783998 | biostudies-literature
Project description:Introduction: MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in post-transcriptional gene regulation and have recently been shown to play a role in cancer metastasis. In solid tumors, especially breast cancer, alterations in miRNA expression contribute to cancer pathogenesis, including metastasis. Considering the emerging role of miRNAs in metastasis, the identification of predictive markers is necessary to further understanding of stage-specific breast cancer development. This is a retrospective analysis that aimed to identify molecular biomarkers related to distant breast cancer metastasis development.<br><br>Methods: A retrospective case cohort study was performed in 64 breast cancer patients treated during the period from 1998-2001. The case group (n=29) consisted of patients with a poor prognosis who presented with breast cancer recurrence or metastasis during follow up. The control group (n=35) consisted of a random sample of patients with a good prognosis who did not develop breast cancer recurrence or metastasis. These patient groups were stratified according to TNM clinical stage (CS) I, II and III, and the main clinical features of the patients were homogeneous. miRNA profiling was performed using formalin-fixed, paraffin-embedded tumors. Biomarkers related to metastatic potential were identified independent of clinical stage, and a cutoff point was selected based on the optimal sensitivity and specificity (ROC curve). Finally, a hazard risk analysis of these biomarkers was performed to evaluate their relation to metastatic potential. <br><br>Results: miRNA expression profiling identified several miRNAs that were either specific and shared across all clinical stages (p?0.05). Among these, we identified miRNAs previously associated with cell motility (let-7 family), cell proliferation and invasion (hsa-miR-16 and has-miR-205) and distant metastasis (hsa-miR-21). In addition, hsa-miR-494 and hsa-miR-21 were up-regulated in metastatic cases of CSI and II. Furthermore, the combination of the 3 miRNAs identified for CSII (hsa-miR-494, hsa-miR-183 and hsa-miR-21) was significant and were a more effective risk marker compared to the single miRNAs. <br><br>Conclusions: Women with metastatic breast cancer, especially CSII, presented up-regulated levels of miR-183, miR-494 and miR-21, which were associated with a poor prognosis. These miRNAs therefore represent new risk biomarkers of breast cancer metastasis and may be useful for future targeted therapies.
2013-08-07 | E-MEXP-3947 | biostudies-arrayexpress
Project description:ObjectiveTo evaluate enzymatic total serum bile acid quantification as a monitoring strategy for women with intrahepatic cholestasis of pregnancy (ICP) treated with ursodeoxycholic acid (UDCA).DesignCohort.SettingOne UK university hospital.Population29 ICP cases treated with UDCA.MethodsSerial samples were collected prospectively throughout gestation. Total serum bile acids were measured enzymatically and individual bile acids by high-performance liquid chromatography-tandem mass spectrometry. Data were log-transformed and analysed with random effects generalised least square regression.Main outcome measuresThe relationship between enzymatic total bile acid measurements and individual bile acid concentrations after UDCA treatment.ResultsIn untreated women, cholic acid was the principal bile acid (51%) and UDCA concentrations were <0.5%, whereas UDCA constituted 60% (IQR 43-69) of serum bile acids following treatment and cholic acid fell to <20%. Changes in the total bile acid measurement reflected similar alterations in the concentrations of the pathologically elevated bile acids, e.g. a two-fold increase in enzymatic total bile acids is accompanied by approximately a two-fold increase in cholic acid and chenodeoxycholic acid at most UDCA doses (P < 0.001). Most of the effects of UDCA on cholic acid occur in the first week of treatment (60% relative reduction, P = 0.025, 95% CI 0.2-0.9, from 10 micromol/l (4.7-17.6) to 3.5 micromol/l (1.4-7.5).ConclusionUrsodeoxycholic acid becomes the main component of the bile acid measurement after treatment. Enzymatic total bile acid assays are good predictors of both cholic acid and chenodeoxycholic acid, the primary bile acids that are raised prior to treatment.Tweetable abstractUrsodeoxycholic acid constitutes approximately 60% of the bile acid measurement and reduces pathological cholic acid in treated women.
| S-EPMC6899621 | biostudies-literature
Project description:Enzymatic assays based on bacterial 3?-hydroxysteroid dehydrogenase are the method of choice for quantification of total bile acids (BAs) in serum. Although non-specific, it is generally considered precise and robust. The aim of this study was to investigate how changes in the BA spectrum might affect the reliability of the method. We measured standard solutions of twenty-three human and murine BAs using a commercial enzymatic assay and compared the measured vs. expected concentrations. Additionally, total BA concentrations in rat and human cholestatic samples with an abnormal BA spectrum were measured using an enzymatic assay, and a more specific LC-MS/MS method. We observed a great variability in the response of individual BAs in the enzymatic assay. Relative signal intensities ranged from 100% in glycocholic acid (reference) to only 20% in ?-muricholic acid. The enzymatic assay markedly underestimated the BA concentrations in both human and rat cholestatic sera when compared to the LC-MS/MS assay. Our study indicated that the performance of an enzymatic assay largely depends on the BA spectrum, and the total concentration of BAs can be markedly underestimated. Samples with an atypical BA spectrum (viz. in rodents) should preferably be measured by other methods.
| S-EPMC7380613 | biostudies-literature
Project description:BACKGROUND & AIMS:The degree of cholestasis is an important disease driver in alcoholic hepatitis, a severe clinical condition that needs new biomarkers and targeted therapies. We aimed to identify the largely unknown mechanisms and biomarkers linked to cholestasis in alcoholic hepatitis. METHODS:Herein, we analyzed a well characterized cohort of patients with alcoholic hepatitis and correlated clinical and histological parameters and outcomes with serum bile acids and fibroblast growth factor 19 (FGF19), a major regulator of bile acid synthesis. RESULTS:We found that total and conjugated bile acids were significantly increased in patients with alcoholic hepatitis compared with controls. Serum FGF19 levels were strongly increased and gene expression of FGF19 was induced in biliary epithelial cells and ductular cells of patients with alcoholic hepatitis. De novo bile acid synthesis (CYP7A1 gene expression and C4 serum levels) was significantly decreased in patients with alcoholic hepatitis. Importantly, total and conjugated bile acids correlated positively with FGF19 and with disease severity (model for end-stage liver disease score). FGF19 correlated best with conjugated cholic acid, and model for end-stage liver disease score best with taurine-conjugated chenodeoxycholic acid. Univariate analysis demonstrated significant associations between FGF19 and bilirubin as well as gamma glutamyl transferase, and negative correlations between FGF19 and fibrosis stage as well as polymorphonuclear leukocyte infiltration, in all patients with alcoholic hepatitis. CONCLUSION:Serum FGF19 and bile acids are significantly increased in patients with alcoholic hepatitis, while de novo bile acid synthesis is suppressed. Modulation of bile acid metabolism or signaling could represent a promising target for treatment of alcoholic hepatitis in humans. LAY SUMMARY:Understanding the underlying mechanisms that drive alcoholic hepatitis is important for the development of new biomarkers and targeted therapies. Herein, we describe a molecule that is increased in patients with alcoholic hepatitis. Modulating the molecular pathway of this molecule might lead to promising targets for the treatment of alcoholic hepatitis.
| S-EPMC6054564 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is a commonly diagnosed malignancy with poor prognosis. Rising incidence of HCC may be due to rising prevalence of metabolic dysfunction-associated fatty liver disease, where altered bile acid metabolism may be implicated in HCC development. Thirty-five bile acids were quantified using ultra-performance liquid chromatography triple-quadrupole mass spectrometry assays in pre-diagnostic serum of 100 HCC cases and 100 matched controls from the Singapore Chinese Health Study. Conditional logistic regression was used to assess associations for bile acid levels with risk of HCC. Conjugated primary bile acids were significantly elevated whereas the ratios of secondary bile acids over primary bile acids were significantly lower in HCC cases than controls. The respective odds ratios and 95% confidence intervals of HCC were 6.09 (1.75-21.21) for highest vs. lowest tertile of cholic acid species and 30.11 (5.88-154.31) for chenodeoxycholic acid species. Doubling ratio of taurine-over glycine-conjugated chenodeoxycholic acid was associated significantly with 40% increased risk of HCC whereas doubling ratio of secondary over primary bile acid species was associated with 30-40% reduced risk of HCC. In conclusion, elevated primary bile acids and taurine over glycine-conjugated ratios were strongly associated with HCC risk whereas the ratios of secondary bile acids over primary bile acids were inversely associated with HCC risk.
| S-EPMC8198655 | biostudies-literature
Project description:BackgroundAs metabolic molecules, bile acids (BAs) not only promote the absorption of fat-soluble nutrients, but they also regulate many metabolic processes, including the homeostasis of glucose and lipids. Although total serum BA (TBA) measurement is a readily available clinical test related to coronary artery disease (CAD), myocardial infarction (MI), and type 2 diabetes mellitus (T2DM), the relationship between TBA and these pathological conditions remain unclear, and research on this topic is inconclusive.MethodsThis study enrolled 20,255 menopausal women aged over 50 years, including 6,421 T2DM patients. The study population was divided into different groups according to the median TBA level in order to explore the clinical characteristics of menopausal women with different TBA levels. Spline analyses, generalized additive model (GAM) model and regression analyses based on TBA level were used to explore the relationship between TBA and different diseases independently, including CAD and MI, or in combination with T2DM.ResultsBoth in the general population and in the T2DM subgroup, the TBA level was significantly lower in CAD patients than in non-CAD patients. Spline analyses indicated that within normal clinical range of TBA concentration (0-10 µmol/L), the presence of CAD and MI showed similar trends in total and T2DM population. Similarly, the GAM model indicated that within the 0-10 μmol/L clinical range, the predicted probability for CAD and MI alone and in combination with T2DM was negatively correlated with TBA concentration. Multivariate regression analysis suggested that low TBA level was positively associated with the occurrence of CAD combined with T2DM (OR: 1.451; 95%CI: 1.141-1.847).ConclusionsIn menopausal women, TBA may represent a valuable clinical serum marker with negative correlation for CAD and MI in patients with T2DM.
| S-EPMC8524089 | biostudies-literature