Structurally different mixed linkage β-glucan supplements differentially increase secondary bile acid excretion in hypercholesterolaemic rat faeces

2020 ◽  
Vol 11 (1) ◽  
pp. 514-523 ◽  
Author(s):  
Nunzia Iaccarino ◽  
Bekzod Khakimov ◽  
Mette Skau Mikkelsen ◽  
Tina Skau Nielsen ◽  
Morten Georg Jensen ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Bile Acid ◽  
Bile Acids ◽  
Acid Excretion ◽  
Secondary Bile Acid ◽  
Bile Acid Excretion ◽  
Secondary Bile Acids

This study demonstrates that structurally different barley β-glucans promote the primary and secondary bile acids’ excretion in a selective manner depending on β-glucans molecular structure.

scholarly journals PSXI-28 Commercial grain-free diet improved taurine status, but increased bile acid excretion when fed to Labrador Retrievers

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 317-318
Author(s):  
Renan Antunes Donadelli ◽  
Julia G Pezzali ◽  
Patrícia M Oba ◽  
Kelly S Swanson ◽  
Craig N Coon ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Whole Blood ◽  
Repeated Measures ◽  
Fecal Excretion ◽  
Feeding Period ◽  
Acid Excretion ◽  
Total Dietary Fiber ◽  
Bile Acid Excretion ◽  
Labrador Retrievers

Abstract In 2018 the Food and Drug Administration (FDA) released a statement that grain-free diets may be related to the increased incidence of dilated cardiomyopathy (DCM) in dogs. This statement was made despite all implicated diets meeting nutrient requirements published by the Association of American Feed Controls Official (AAFCO) and enforced by State Officials. Many of these dogs presented with low plasma or whole blood taurine concentrations, and as such, we hypothesized that feeding these diets would result in reduced taurine status over a 26 wk feeding period. The objective of this study was to determine the effects of feeding a grain-free diet to large breed dogs on taurine status and overall health. Eight Labrador Retrievers (4 males, 4 females; Four Rivers Kennel, MO) were individually housed and fed a commercial complete and balanced grain-free diet (Acana Pork and Squash formula; APS; moisture 8.40%, crude protein 37.81%, crude fat 18.78%, ash 8.06%, and total dietary fiber 11.40%) for 26 weeks. Fasted blood samples were collected at week 0 and 26 for analyses of plasma and whole blood taurine. Urine was collected by free catch and analyzed for taurine and creatinine. Fresh fecal samples were collected and analyzed for bile acids. Data were analyzed using the GLIMMIX procedure with repeated measures in SAS (v. 9.4). Dogs were healthy throughout the duration of the trial. Urinary taurine to creatinine ratio did not change throughout the feeding period (wk 0 = 0.25 vs. wk 26 = 0.28). Fecal bile acid excretion increased after 26 weeks of feeding APS to dogs. Despite the higher fecal excretion of bile acids, plasma and whole blood taurine increased over the 26 wk feeding period. In conclusion, feeding APS for 26 wk results in increased taurine status in large breed dogs, despite higher excretion of fecal bile acids.

Identification of unique bile acid-metabolizing bacteria from the microbiome of centenarians

2020 ◽  
Author(s):  
Kenya Honda ◽  
Yuko Sato ◽  
Koji Atarashi ◽  
Damian Plichta ◽  
Yasumichi Arai ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Lithocholic Acid ◽  
Multidrug Resistant ◽  
Bile Acid Metabolism ◽  
Critical Determinant ◽  
Secondary Bile Acid ◽  
Clostridioides Difficile ◽  
Vancomycin Resistant ◽  
Secondary Bile Acids

Abstract Centenarians, or individuals who have lived more than a century, represent the ultimate model of successful longevity associated with decreased susceptibility to ageing-associated illness and chronic inflammation. The gut microbiota is considered to be a critical determinant of human health and longevity. Here we show that centenarians (average 107 yo) have a distinct gut microbiome enriched in microbes capable of generating unique secondary bile acids, including iso-, 3-oxo-, and isoallo-lithocholic acid (LCA), as compared to elderly (85-89 yo) and young (21-55 yo) controls. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from a centenarian’s faecal microbiota, we identified Parabacteroides merdae and Odoribacteraceae strains as effective producers of isoalloLCA. Furthermore, we generated and tested mutant strains of P. merdae to show that the enzymes 5α-reductase (5AR) and 3β-hydroxysteroid dehydrogenase (3βHSDH) were responsible for isoalloLCA production. This secondary bile acid derivative exerted the most potent antimicrobial effects among the tested bile acid compounds against gram-positive (but not gram-negative) multidrug-resistant pathogens, including Clostridioides difficile and vancomycin-resistant Enterococcus faecium. These findings suggest that specific bile acid metabolism may be involved in reducing the risk of pathobiont infection, thereby potentially contributing to longevity.

Plasma Lathosterol as a Screening Test for Bile Acid Malabsorption Due to Ileal Resection: Correlation with 75SeHCAT Test and Faecal Bile Acid Excretion

1996 ◽  
Vol 90 (4) ◽  
pp. 315-319 ◽  
Author(s):  
M. A. Färkkilä ◽  
K. J. Kairemo ◽  
M. J. Taavitsainen ◽  
T. A. Strandberg ◽  
T. A. Miettinen
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Half Life ◽  
Screening Test ◽  
Acid Excretion ◽  
Bile Acid Malabsorption ◽  
Bile Acid Excretion ◽  
Control Subjects ◽  
Biological Half Life ◽  
Schilling Test

1. Plasma lathosterol concentration, known to reflect cholesterol and bile acid synthesis, was evaluated as a screening test for bile acid malabsorption, comparing it with faecal bile acid measurements, SeHCAT test and Schilling test in 22 subjects of whom six were healthy controls and 16 had Crohn's disease with ileal resections of varying length. 2. Plasma lathosterols and other non-cholesterol sterols were determined by GLC. Faecal bile acids were measured by GLC, and SeHCAT retention times by gamma camera. The study subjects were divided into two groups according to the degree of bile acid malabsorption: controls (faecal bile acids<10 mg day−1 kg−1, n = 9) and bile acid malabsorption (faecal bile acids > 10 mg day−1 kg−1, n = 13). 3. Faecal bile acid excretion was 5.9 ± 1.0 mg day−1 kg−1 in control subjects and 45.7 ± 6.1 mg day−1 kg−1 in the bile acid malabsorption group. The biological half-life of 75SeHCAT (T½) was 95.6 ± 16.3 h and 14.1 ± 4.1 h, respectively. Plasma lathosterol levels were significantly elevated in patients with bile acid malabsorption (742 ± 84 μg/ml compared with 400 ± 59 μg/ml in control subjects) and correlated closely with faecal bile acid levels (r = 0.779, P<0.001), with 75SeHCAT T½ (r = −0.524, P<0.05) and with Schilling test (r = −0.591, P<0.05). Significant correlations were also obtained for Δ8-cholestenol with faecal bile acids (r = 0.784, P<0.001) and 75SeHCAT (r = −0.505, P<0.05). The biological half-life of SeHCAT correlated with faecal bile acid excretion (r = −0.702, P<0.01). Using mean + 2 SD of lathosterol (In μg/ml cholesterol) as a cut-off value and 10 mg day−1 kg−1 as the upper limit for faecal bile acid excretion, the test gives 100% sensitivity and 82% specificity for plasma lathosterol determination to detect bile acid malabsorption. 4. The results indicate that both the 75SeHCAT test and plasma lathosterol detect bile acid malabsorption in patients with ileal resections for Crohn's disease. However, plasma lathosterol is a simpler and less expensive method.

Bile Flow and Composition During Bile Acid Depletion and Administration

1974 ◽  
Vol 52 (2) ◽  
pp. 334-348 ◽  
Author(s):  
Curtis D. Klaassen
Keyword(s):  
Bile Acid ◽  
Bile Salt ◽  
Bile Acids ◽  
Bile Flow ◽  
Enterohepatic Circulation ◽  
Acid Excretion ◽  
Bile Formation ◽  
Bile Acid Excretion ◽  
Rat Bile ◽  
Acid Administration

Relatively similar concentrations of the inorganic ions were detected in rat, rabbit, and dog bile; however, dog bile had a higher concentration of protein, cholesterol, phospholipid phosphorous, and percentage solids than rat bile, and rabbit bile had the lowest concentration. The biliary excretion of bile acids was altered in each species by: (1) interruption of the enterohepatic circulation; (2) rapid administration of an exogenous load of bile acids; and (3) constant infusion of an exogenous load of bile acids. Bile acid and phospholipid phosphorous concentration and percentage solids increased after bile acid administration in all three species; however, species differences in bilirubin concentration were observed and a marked decrease was detected in rabbit and dog bile but it markedly increased in rat bile. When the enterohepatic circulation was interrupted in the dog and rat, the bile acid concentration markedly decreased with only minor changes in bile flow. This not only supports the theory that there is a bile salt independent fraction of bile formation, but also demonstrates that canalicular bile formation can be maintained at relatively normal rates with almost no excretion of bile acids. Marked discrepancy between bile acid excretion and bile flow was observed in the rat after bile acid administration, in that a marked increase in bile acid excretion was observed but little or no increase in flow. When bile flow was plotted against bile acid excretion for the three species, the slope of the line was less during bile acid administration than during depletion, indicating that the bile acids are accompanied by less water during bile acid administration than during depletion. Variation in the bile flow intercept with zero bile acid excretion (thought to represent the bile salt-independent fraction) was relatively large, which is probably due in part to alteration in the production of the bile salt independent fraction when bile acid secretion is altered. It appears that both the choleretic property of bile acids varies during various rates of bile acid excretion and the bile salt-independent fraction is not constant. Therefore, calculation of the bile salt independent fraction as previously performed should be interpreted with extreme caution. Thus, it appears difficult to determine the quantitative importance of bile acid excretion in bile formation.

scholarly journals Antibiotic-Induced Alterations of the Gut Microbiota Alter Secondary Bile Acid Production and Allow for Clostridium difficile Spore Germination and Outgrowth in the Large Intestine

mSphere ◽  
2016 ◽  
Vol 1 (1) ◽  
Author(s):  
Casey M. Theriot ◽  
Alison A. Bowman ◽  
Vincent B. Young
Keyword(s):  
Bile Acid ◽  
Clostridium Difficile ◽  
Gut Microbiota ◽  
Bile Acids ◽  
Large Intestine ◽  
Spore Germination ◽  
Secondary Bile Acid ◽  
Content Type ◽  
Secondary Bile Acids

ABSTRACT Antibiotics alter the gastrointestinal microbiota, allowing for Clostridium difficile infection, which is a significant public health problem. Changes in the structure of the gut microbiota alter the metabolome, specifically the production of secondary bile acids. Specific bile acids are able to initiate C. difficile spore germination and also inhibit C. difficile growth in vitro, although no study to date has defined physiologically relevant bile acids in the gastrointestinal tract. In this study, we define the bile acids C. difficile spores encounter in the small and large intestines before and after various antibiotic treatments. Antibiotics that alter the gut microbiota and deplete secondary bile acid production allow C. difficile colonization, representing a mechanism of colonization resistance. Multiple secondary bile acids in the large intestine were able to inhibit C. difficile spore germination and growth at physiological concentrations and represent new targets to combat C. difficile in the large intestine. It is hypothesized that the depletion of microbial members responsible for converting primary bile acids into secondary bile acids reduces resistance to Clostridium difficile colonization. To date, inhibition of C. difficile growth by secondary bile acids has only been shown in vitro. Using targeted bile acid metabolomics, we sought to define the physiologically relevant concentrations of primary and secondary bile acids present in the murine small and large intestinal tracts and how these impact C. difficile dynamics. We treated mice with a variety of antibiotics to create distinct microbial and metabolic (bile acid) environments and directly tested their ability to support or inhibit C. difficile spore germination and outgrowth ex vivo. Susceptibility to C. difficile in the large intestine was observed only after specific broad-spectrum antibiotic treatment (cefoperazone, clindamycin, and vancomycin) and was accompanied by a significant loss of secondary bile acids (deoxycholate, lithocholate, ursodeoxycholate, hyodeoxycholate, and ω-muricholate). These changes were correlated to the loss of specific microbiota community members, the Lachnospiraceae and Ruminococcaceae families. Additionally, physiological concentrations of secondary bile acids present during C. difficile resistance were able to inhibit spore germination and outgrowth in vitro. Interestingly, we observed that C. difficile spore germination and outgrowth were supported constantly in murine small intestinal content regardless of antibiotic perturbation, suggesting that targeting growth of C. difficile will prove most important for future therapeutics and that antibiotic-related changes are organ specific. Understanding how the gut microbiota regulates bile acids throughout the intestine will aid the development of future therapies for C. difficile infection and other metabolically relevant disorders such as obesity and diabetes. IMPORTANCE Antibiotics alter the gastrointestinal microbiota, allowing for Clostridium difficile infection, which is a significant public health problem. Changes in the structure of the gut microbiota alter the metabolome, specifically the production of secondary bile acids. Specific bile acids are able to initiate C. difficile spore germination and also inhibit C. difficile growth in vitro, although no study to date has defined physiologically relevant bile acids in the gastrointestinal tract. In this study, we define the bile acids C. difficile spores encounter in the small and large intestines before and after various antibiotic treatments. Antibiotics that alter the gut microbiota and deplete secondary bile acid production allow C. difficile colonization, representing a mechanism of colonization resistance. Multiple secondary bile acids in the large intestine were able to inhibit C. difficile spore germination and growth at physiological concentrations and represent new targets to combat C. difficile in the large intestine.

scholarly journals Strain-dependent inhibition of Clostridioides difficile by commensal Clostridia encoding the bile acid inducible (bai) operon

2020 ◽  
Author(s):  
A.D. Reed ◽  
M.A. Nethery ◽  
A. Stewart ◽  
R. Barrangou ◽  
C.M. Theriot
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Culture System ◽  
Dependent Manner ◽  
Secondary Bile Acid ◽  
Clostridioides Difficile ◽  
The Relationship ◽  
Strain Dependent ◽  
Secondary Bile Acids

AbstractClostridioides difficile is one of the leading causes of antibiotic-associated diarrhea. Gut microbiota-derived secondary bile acids and commensal Clostridia that encode the bile acid inducible (bai) operon are associated with protection from C. difficile infection (CDI), although the mechanism is not known. In this study we hypothesized that commensal Clostridia are important for providing colonization resistance against C. difficile due to their ability to produce secondary bile acids, as well as potentially competing against C. difficile for similar nutrients. To test this hypothesis, we examined the ability of four commensal Clostridia encoding the bai operon (C. scindens VPI 12708, C. scindens ATCC 35704, C. hiranonis, and C. hylemonae) to convert CA to DCA in vitro, and if the amount of DCA produced was sufficient to inhibit growth of a clinically relevant C. difficile strain. We also investigated the competitive relationship between these commensals and C. difficile using an in vitro co-culture system. We found that inhibition of C. difficile growth by commensal Clostridia supplemented with CA was strain-dependent, correlated with the production of ∼2 mM DCA, and increased expression of bai operon genes. We also found that C. difficile was able to outcompete all four commensal Clostridia in an in vitro co-culture system. These studies are instrumental in understanding the relationship between commensal Clostridia and C. difficile in the gut, which is vital for designing targeted bacterial therapeutics. Future studies dissecting the regulation of the bai operon in vitro and in vivo and how this affects CDI will be important.ImportanceCommensal Clostridia encoding the bai operon such as C. scindens have been associated with protection against CDI, however the mechanism for this protection is unknown. Herein, we show four commensal Clostridia that encode the bai operon effect C. difficile growth in a strain-dependent manner, with and without the addition of cholate. Inhibition of C. difficile by commensals correlated with the efficient conversion of cholate to deoxycholate, a secondary bile acid that inhibits C. difficile germination, growth, and toxin production. Competition studies also revealed that C. difficile was able to outcompete the commensals in an in vitro co-culture system. These studies are instrumental in understanding the relationship between commensal Clostridia and C. difficile in the gut, which is vital for designing targeted bacterial therapeutics.

Relation between dietary cholesterol and bile acid excretion in the rat

1962 ◽  
Vol 203 (6) ◽  
pp. 1029-1032 ◽  
Author(s):  
Jean D. Wilson
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Dietary Cholesterol ◽  
Acid Synthesis ◽  
Cholesterol Content ◽  
Bile Acid Synthesis ◽  
Fecal Excretion ◽  
Acid Excretion ◽  
Cholesterol Feeding ◽  
Bile Acid Excretion

The influence of dietary cholesterol on fecal excretion of bile acids has been studied in rats fed isocaloric quantities of purified diets that varied only in cholesterol content. Addition of dietary cholesterol clearly resulted in an increase in excretion of total bile acids, as well as in conversion of cholesterol-4-C14 to bile acid-C14. An acceleration in bile acid excretion as a result of cholesterol feeding was demonstrated to be independent of dietary cholic acid and to occur despite suppression of the bowel flora. These results suggest that not only does absorbed dietary cholesterol play a role in determining the rate of bile acid formation but that the adaptation of bile acid synthesis to cholesterol feeding may in part be a determining factor in the varying response of different species to cholesterol feeding.

scholarly journals Temporal Fluctuations of Gut Microbiota and Bile Acid Metabolism in Critically Ill Children

2021 ◽  
Author(s):  
Iain Robert Louis Kean ◽  
Josef Wagner ◽  
Anisha Wijeyesekera ◽  
Marcus de Goffau ◽  
Sarah Thurston ◽  
...  
Keyword(s):  
Bile Acid ◽  
Critical Illness ◽  
Gut Microbiota ◽  
Bile Acids ◽  
Critically Ill ◽  
Critically Ill Children ◽  
Bile Acid Metabolism ◽  
Rrna Gene ◽  
Secondary Bile Acid ◽  
Secondary Bile Acids

Abstract Background: Critical illness frequently requires the use of broad-spectrum antimicrobials to treat life-threatening infection. The resulting impact on microbiome diversity is profound, influencing gastrointestinal fermentation endpoints, host immune response and metabolic activity including the conversion of primary bile acids to secondary bile acids. We previously observed reduced fermentation capacity in the gut microbiota of critically ill children upon hospital admission, but the functional recovery trajectory of the paediatric gut microbiome during critical illness has not been well defined. Here, we longitudinally studied the intestinal microbiome and faecal bile acid profile of critically ill children during hospitalisation in a paediatric intensive care unit (PICU). The composition of the microbiome was determined by sequencing of the 16s rRNA gene, and bile acids were measured from faecal water by liquid chromatography hyphenated to mass spectrometry. Results: In comparison to admission faecal samples, members of Clostridium cluster XIVa and Lachnospiraceae recovered during the late-acute phase (days 8-10) of hospitalisation. Patients with infections had a lower proportion of Lachnospiraceae in their gut microbiota than control microbiota and patients with admitting diagnoses. The proportion of Recovery Associated Bacteria (RAB) was observed to decline with the length of PICU admission. Additionally, the proportions of RAB were reduced in those with systemic infection, respiratory failure, and undergoing surgery. Notably, Clostridioides were positively associated with the secondary bile acid deoxycholic acid, which we hypothesised to driven by secondary bile acid induced sporulation; the ratio of primary to secondary bile acids demonstrated recovery during critical illness. Conclusion: The recovery of secondary bile acids occurs quickly after intervention for critical illness. Bile acid recovery may be induced by the Lachnospiraceae , the composition of which shifts during critical illness. Our data suggest that gut health and early gut microbiota recovery can be assessed by readily quantifiable faecal bile acid profiles.

scholarly journals The influence of probiotics on individual fecal secondary bile acid levels: a two-case study of schizophrenic patients receiving an atypical antipsychotic drug

2017 ◽  
Vol 7 (11) ◽  
pp. 849
Author(s):  
Yosuke Saito ◽  
Hiroyuki Nishimiya ◽  
Yasue Kondo ◽  
Toyoaki Sagae
Keyword(s):  
Bile Acid ◽  
Bile Salt ◽  
Bile Acids ◽  
Acid Metabolism ◽  
Bile Acid Metabolism ◽  
Bile Salt Hydrolase ◽  
Atypical Antipsychotic Drug ◽  
Secondary Bile Acid ◽  
Secondary Bile Acids ◽  
Bsh Activity

Background: Probiotics is used as a promising approach in the prevention and treatment of hypercholesterolemia. Modification of bile acid metabolism through the deconjugation of bile salts by microbial bile salt hydrolase (BSH) is considered to be the core mechanism of the hypocholesterolemic effects of probiotics. Nevertheless, BSH activity is reported to be detrimental to the human host due to the generation of toxic secondary bile acids. Thus, the influence of probiotic intake on bile acid metabolism needs to be elucidated. We analyzed the bile acid levels and microbiota in human fecal samples after probiotic supplementation to assess the influence of probiotic intake on fecal bile acid levels. Two patients hospitalized for schizophrenia and dyslipidemia, receiving an atypical antipsychotic drug, were enrolled in this study (Subjects A and B). Both subjects received Lactobacillus rhamnosus GG (LGG) for 4 weeks, and no probiotics for the following 4 weeks. Fecal samples were collected at baseline and after 4 and 8 weeks.Results: Conjugated bile acids may be modified by indigenous intestinal bacteria into unconjugated bile acids and secondary bile acids through deconjugation reactions by BSH activity and the subsequent 7a-dehydroxylation pathway, respectively. In the fecal microbiota from Subject A, the relative abundance of Bifidobacterium increased after LGG supplementation (30%–49%). Most Bifidobacterium and Lactobacillus strains that colonize mammalian intestines may report BSH activity, and in general bifidobacteria reveals a higher BSH activity than lactobacilli. The fecal unconjugated bile acid and secondary bile acid levels in Subject A increased after the LGG supplementation (0.36–1.79 and 1.82–16.19 mmol/g respectively). Although the LGG supplementation appears to promote bile acid deconjugation, most of the unconjugated bile acids in Subject A appear to have been modified into secondary bile acids. Alternatively, in Subject B there were no significant changes throughout the study.Conclusion: We observed a significant increase in the fecal secondary bile acid levels after probiotic administration in one of our cases. Further studies are needed to elucidate the factors affecting 7a-dehydroxylation of bile acids to confirm the safety of using probiotics.Keywords: bile salt hydrolase; BSH; dihydroxylation; Bifidobacterium

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