scholarly journals Evaluating Hepatobiliary Transport with 18F-Labeled Bile Acids: The Effect of Radiolabel Position and Bile Acid Structure on Radiosynthesis and In Vitro and In Vivo Performance

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Stef De Lombaerde ◽  
Ken Kersemans ◽  
Sara Neyt ◽  
Jeroen Verhoeven ◽  
Christian Vanhove ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Membrane Vesicles ◽  
Hepatic Uptake ◽  
Hepatobiliary Transport ◽  
Bile Acid Transporters ◽  
Significant Difference ◽  
The Impact

Introduction. An in vivo determination of bile acid hepatobiliary transport efficiency can be of use in liver disease and preclinical drug development. Given the increased interest in bile acid Positron Emission Tomography- (PET-) imaging, a further understanding of the impact of 18-fluorine substitution on bile acid handling in vitro and in vivo can be of significance. Methods. A number of bile acid analogues were conceived for nucleophilic substitution with [18F]fluoride: cholic acid analogues of which the 3-, 7-, or 12-OH function is substituted with a fluorine atom (3α-[18F]FCA; 7β-[18F]FCA; 12β-[18F]FCA); a glycocholic and chenodeoxycholic acid analogue, substituted on the 3-position (3β-[18F]FGCA and 3β-[18F]FCDCA, resp.). Uptake by the bile acid transporters NTCP and OATP1B1 was evaluated with competition assays in transfected CHO and HEK cell lines and efflux by BSEP in membrane vesicles. PET-scans with the tracers were performed in wild-type mice (n=3 per group): hepatobiliary transport was monitored and compared to a reference tracer, namely, 3β-[18F]FCA. Results. Compounds 3α-[18F]FCA, 3β-[18F]FGCA, and 3β-[18F]FCDCA were synthesized in moderate radiochemical yields (4–10% n.d.c.) and high radiochemical purity (>99%); 7β-[18F]FCA and 12β-[18F]FCA could not be synthesized and included further in this study. In vitro evaluation showed that 3α-FCA, 3β-FGCA, and 3β-FCDCA all had a low micromolar Ki-value for NTCP, OATP1B1, and BSEP. In vivo, 3α-[18F]FCA, 3β-[18F]FGCA, and 3β-[18F]FCDCA displayed hepatobiliary transport with varying efficiency. A slight yet significant difference in uptake and efflux rate was noticed between the 3α-[18F]FCA and 3β-[18F]FCA epimers. Conjugation of 3β-[18F]FCA with glycine had no significant effect in vivo. Compound 3β-[18F]FCDCA showed a significantly slower hepatic uptake and efflux towards gallbladder and intestines. Conclusion. A set of 18F labeled bile acids was synthesized that are substrates of the bile acid transporters in vitro and in vivo and can serve as PET-biomarkers for hepatobiliary transport of bile acids.

scholarly journals Downregulation of CTRP-3 by Weight Loss In Vivo and by Bile Acids and Incretins in Adipocytes In Vitro

2020 ◽  
Vol 21 (21) ◽  
pp. 8168
Author(s):  
Andreas Schmid ◽  
Jonas Gehl ◽  
Miriam Thomalla ◽  
Alexandra Hochberg ◽  
Anja Kreiß ◽  
...  
Keyword(s):  
Weight Loss ◽  
Bile Acid ◽  
Bile Acids ◽  
Serum Levels ◽  
Receptor Expression ◽  
Low Calorie Diet ◽  
Calorie Diet ◽  
Bile Acid Receptor

The adipokine CTRP-3 (C1q/TNF-related protein-3) exerts anti-inflammatory and anti-diabetic effects. Its regulation in obesity and during weight loss is unknown. Serum and adipose tissue (AT) samples were obtained from patients (n = 179) undergoing bariatric surgery (BS). Moreover, patients (n = 131) participating in a low-calorie diet (LCD) program were studied. CTRP 3 levels were quantified by ELISA and mRNA expression was analyzed in AT and in 3T3-L1 adipocytes treated with bile acids and incretins. There was a persistent downregulation of CTRP-3 serum levels during weight loss. CTRP-3 expression was higher in subcutaneous than in visceral AT and serum levels of CTRP-3 were positively related to AT expression levels. A rapid decrease of circulating CTRP-3 was observed immediately upon BS, suggesting weight loss-independent regulatory mechanisms. Adipocytes CTRP-3 expression was inhibited by primary bile acid species and GLP 1. Adipocyte-specific CTRP-3 deficiency increased bile acid receptor expression. Circulating CTRP-3 levels are downregulated during weight loss, with a considerable decline occurring immediately upon BS. Mechanisms dependent and independent of weight loss cause the post-surgical decline of CTRP-3. The data strongly argue for regulatory interrelations of CTRP-3 with bile acids and incretin system.

Comparison of the Predictive Value of MRD and PVA Score in Pediatric ALL.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1520-1520
Author(s):  
Anja Troeger ◽  
Gabriele Escherich ◽  
Udo zur Stadt ◽  
M. L Den Boer ◽  
Rob Pieters ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Correlation Coefficient ◽  
Predictive Value ◽  
Genetic Alterations ◽  
Relevant Parameter ◽  
Response To Chemotherapy ◽  
Significant Difference ◽  
The Impact

Abstract Early identification of patients (pts) at risk for relapse allows for development of risk-adapted treatment strategies, thus steadily improving the outcome in pediatric acute lymphoblastic leukemia (ALL). Besides classic prognostic factors such as age, initial leukocyte count (WBC), genetic alterations and the immune phenotype, the so called PVA Score, summarizing the in vitro resistance of blasts against prednisone, vincristine and asparaginase, has been applied for treatment stratification in the CoALL protocol, a German multicenter study for children with ALL. Over the past years it has become increasingly clear that the in vivo response to chemotherapy assessed by detection of residual malignant cells (MRD) by PCR technique can be predictive of prognosis. Here we compare for the first time the relevance of in vitro (PVA Score) and in vivo (MRD) treatment response in a large cohort of 275 children with ALL, age 1–17 years, uniformly treated according to the CoALL protocols 05–92 to 07–03. Children with B cell precursor ALL (BCP-ALL) and T-ALL were analyzed separately. Bone marrow samples of 160 children with BCP-ALL and of 115 T-ALL pts diagnosed between 1992–2005 were prospectively assessed for PVA Score at diagnosis and MRD levels at day (d) 15, 29 and 43 after informed consent was obtained from the parents or legal guardians at the time of enrolment. Of note, 7 of the BCP-ALL and 14 of the T-ALL pts with late morphological response were excluded from analysis. Overall median MRD levels in BCP-ALL pts (MRDd15: 6×10e-4; MRDd29: 2×10e-5) were one log lower than in T-ALL (MRDd15: 9×10e-3; MRDd29: 3×10e-4). We detected no association between PVA Score and MRD level in BCP-ALL (correlation coefficient: r=0.15; p=0.15) and only a weak correlation in T-ALL pts (correlation coefficient: r=0.43; p=0.0003). When assessing the impact of the PVA Score on relapse free survival (RFS), in BCP-ALL only score 3+4 (good response) vs. 8+9 (poor response) was prognostically relevant (RFS 0.86±0.05 vs. 0.59±0.12; p=0.03), whereas in T-ALL no significant difference between these subgroups was found (RFS 0.71±0.1 vs. 0.68±0.1; p=0.62). In multivariate analysis PVA Score 3+4 vs. 8+9 remained the most relevant parameter for RFS in BCP-ALL (p=0.05) when compared to age and initial WBC. However, MRD levels were of even higher predictive power, especially at later time points: MRD negativity at d29 in BCP-ALL identified pts with significantly superior RFS (RFS MRD neg.: 0.9±0.05 vs. pos.: 0.7±0.05; p=0.003) and low MRD levels indicated a favorable outcome in T-ALL (RFS MRD <10e-3: 0.89±0.05 vs. MRD >10e-3: 0.68±0.07; p=0.001). Moreover, both BCP-ALL and T-ALL pts characterized by MRD levels >10e-3 on d43 exhibited a poor outcome (RFS BCP-ALL: 0.42±0.17; RFS T-ALL: 0.47±0.14). MRD remained an independent marker in multivariate analysis including initial WBC and age, both in BCP- (MRDd29: p=0.006; MRDd43: p=0.001) and T-ALL (MRDd29: p=0.003; MRDd43: p=0.015). By multivariate analysis, in T-ALL low MRD levels on d29 predicted superior RFS independently from the PVA Score (MRD: p=0.002 vs. PVA: p=0.09), whereas in BPC-ALL these parameters were not completely independent from each other at that early time point (MRD: p= 0.059 vs. PVA: p= 0.063) but became independent at d43 (MRD: p= 0.018 vs. PVA: p= 0.253). While the predictive value of the PVA Score was limited to BCP-ALL, MRD was an independent prognostic marker for both BCP- and T-ALL and reliably identified pts at low and high risk for relapse.

On-Line Hemodiafiltration with Pre- and Postdilution: A Comparison of Efficacy

1997 ◽  
Vol 20 (2) ◽  
pp. 81-90 ◽  
Author(s):  
P. Ahrenholz ◽  
R.E. Winkler ◽  
W. Ramlow ◽  
M. Tiess ◽  
W. Müller
Keyword(s):  
Molecular Weight ◽  
Theoretical Description ◽  
Convective Transport ◽  
Small Molecular Weight ◽  
Dialysate Flow ◽  
Significant Difference ◽  
On Line ◽  
The Impact

Since the introduction of on-line substituate preparation, high substituate rates (Qs) in pre- and postdilution for hemodiafiltration (HDF) procedures can be realized. During postdilution HDF (POD-HDF) and additional convective removal is possible, but in vivo Qs is limited to approx. 1/3Qb (bloodflow). With predilution HDF (PRD-HDF) higher Qs and therefore high convective transport rates by ultrafiltration can be reached. On the other hand the blood concentration is diminished by predilution. Further decrease of the diffusive transport is caused by reduced dialysate flow Qd due to separation of the substituate from the dialysate (Fresenius 4008 On-Line HDF, Gambro AK100 Ultra). The theoretical description of the combined diffusive-convective transport is limited to 1-dimensional models and small UF-rates. Therefore for practical and theoretical purposes the assessment of the efficacy of on-line PRD-HDF and POD-HDF in different molecular weight ranges is desirable. By means of in vitro experiments the effective clearances Keff of hemodialysis (HD, dialyzer: Fresenius F60) for urea, creatinine, vitamin B12 and inulin were compared with measured and theoretical Keff of POD- and PRD-HDF. The theoretical expectation is confirmed that Keff for small molecular weight substances decreases slightly with PRD-HDF and increases for larger molecules. In the case of POD-HDF Keff for small molecular weight substances increases slightly and strongly for larger molecules. In vivo experiments were performed to measure the real substance removal from patient's blood and to figure out the impact of dialysate flow (collection of the used dialysate during the 1. treatment hour and concentration measurements for urea, creatinine, phosphate, ß2-MG). The results show that the substraction of Qs from Qd reduces Keff for urea, creatinine and phosphate but not for ß2-MG. PRD-HDF with Qd = 500 ml/min is significantly less effective for small molecules than HD. There is no significant difference of Keff for urea, creatinine, phosphate during HD and PRD-HDF with Qd = 800 ml/min, but a significant increase of 10-15% for POD-HDF Keff for ß2-MG increases by 75% for PRD-HDF and 95% for POD-HDF compared with HD (Qd = 500 ml/min).

Trastuzumab versus MYL-1401O (a proposed trastuzumab biosimilar) in a phase I bioequivalence study: In vivo and in vitro immunomodulation.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 10-10
Author(s):  
Régine Audran ◽  
Haithem Chtioui ◽  
Anne-Christine Thierry ◽  
Carole Mayor ◽  
Laure Vallotton ◽  
...  
Keyword(s):  
Phase I ◽  
Mononuclear Cell ◽  
Ex Vivo ◽  
Reference Drug ◽  
Gm Csf ◽  
Significant Difference ◽  
Ifn Γ ◽  
The Impact

10 Background: Trastuzumab is a humanized monoclonal antibody targeting breast cancer cells overexpressing the HER2-oncoprotein. During a Phase-I single centre, single dose, randomized, double-blind, cross-over study assessing the bioequivalence of a proposed trastuzumab biosimilar (MYL-1401O) versus the initially marketed drug (Herceptin), we investigated in addition a large panel of pharmacodynamics parameters comparing the immunomodulatory activity of both drugs. Methods: 22 healthy males were included, 19 subjects receiving randomly a single intravenous infusion of MYL-1401O and 22 of Herceptin, separated by 16 to 22 week wash-out. Blood samples drawn pre- and post- infusion were assessed for in vivo serum cytokines induction (IL-1β, IL-2, IL-6, IL-10, IL-12, TNF-α, GM-CSF and IFN-γ) whereas the impact of treatment on mononuclear cell subsets and their level of activation was tested ex vivo. Volunteers’ PBMC (peripheral blood monocnuclear cells) were stimulated in vitro with recall antigens and mitogen for cytokine production. At baseline, we performed in addition a cytokine release assay on PBMC upon stimulation with trastuzumab as a preclinical safety test. Results: Trastuzumab infusion induced a transient and weak peak of serum IL-6 at 6h, and a modulation of mononuclear cell subset profile and level of activation. Notably CD16+ cells frequency decreased at 3h and peaked at 48h. Except for CD8+ T cells, there were no significant differences between Herceptin and its proposed biosimilar ex vivo. PBMC stimulated in vitro with trastuzumab secreted IL-6, TNF-a, IL-1β, GM-CSF, IFN-γ, and IL-10, but no IL-2. There was no significant difference between the two mAbs. Conclusions: Based on these in vivo, ex vivo and in vitro experiments, there is a strong assumption that MYL-1401O is biosimilar to the reference drug Herceptin for its immunomodulation properties as already proven for its bioequivalence. Clinical trial information: 2011-001406-94.

scholarly journals Ileal bile acid transporter inhibition, CYP7A1 induction, and antilipemic action of 264W94

2002 ◽  
Vol 43 (8) ◽  
pp. 1320-1330 ◽  
Author(s):  
Carolyn Root ◽  
Chari D. Smith ◽  
Scott S. Sundseth ◽  
Heather M. Pink ◽  
Joan G. Wilson ◽  
...  
Keyword(s):  
Bile Acid ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Membrane Vesicles ◽  
Human Model ◽  
Diurnal Fluctuation ◽  
Bile Acid Transporter ◽  
Acid Transporter

264W94 was designed to inhibit the ileal bile acid transporter (IBAT). Evaluated in vitro, 264W94 dose-dependently inhibited sodium-dependent uptake of 10 μM [3H]taurocholic acid (TC) by rat and monkey brush border membrane vesicles with IC50s of 0.24 μM and 0.41 μM, and had a competitive profile with Ki of 0.2 μM against TC in Chinese hamster ovary cells expressing human IBAT. In distal ileum in situ, 1–10 μM of 264W94 rapidly decreased uptake of 3mM TC by 24–39%, with corresponding decreases in biliary recovery. In rats and mice in vivo, oral 264W94 decreased absorption of TC analog, 23,25-75Se-homocholic acid taurine (75SeHCAT; quantitated in feces), with ED30 of 0.02 mg/kg bid. 75SeHCAT traced through the GI-tract revealed that peak (97%) inhibition of 75SeHCAT absorption by the distal quarter of small intestine occurred at 4 h after single dose of 264W94 (0.1 mg/kg). Inhibition of IBAT by 264W94 in rats was associated with compensatory, same-day, 4-fold induction of hepatic cholesterol 7α-hydroxylase (CYP7A1) activity, exhibiting normal diurnal fluctuation for 3 days of dosing. In diet induced hypercholesterolemic rats, 264W94 (0.03–1.0 mg/kg bid) dose-dependently reduced serum LDL+VLDL cholesterol up to 61%.In conclusion, 264W94 is a potent new cholesterol lowering agent that acts through inhibition of IBAT and exhibits activity in a human model.

The Development of a new Hemoperfusion Column: The Filmadsorber

1982 ◽  
Vol 5 (3) ◽  
pp. 181-184 ◽  
Author(s):  
Ad van Berlo ◽  
Ad Verkooyen ◽  
A. Tangerman
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Bile Ducts ◽  
Average Diameter ◽  
In Vitro Studies ◽  
In Vivo Studies ◽  
Different Types ◽  
Collodion Film

A hemoperfusion system has been developed in wich very small charcoal particles (average diameter 40 μm) are embedded and immobilized in a collodion film (Filmadsorber). In vitro studies revealed that the absorption of bile acids by these small charcoal particles is superior to that by larger ones (size: 0.5 to 5 mm) as used in commercially available adsorbers. In vivo studies confirmed these results: dogs with ligated bile ducts were subjected to hemoperfusion through different types of charcoal adsorbers. Bile acid clearances of filmadsorbers containing less charcoal than the commercials were significantly higher.

Depletion of Bile Acids and Bilirubin in Dogs with Biliary Obstruction by Plasmaperfusion of Usp-Charcoal-Coated Glass Beads

1980 ◽  
Vol 3 (5) ◽  
pp. 281-285 ◽  
Author(s):  
B.H. Lauterburg ◽  
E.R. Dickson ◽  
A.A. Pineda ◽  
H.F. Taswell
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Glass Beads ◽  
Bile Acid Concentration ◽  
Coated Glass ◽  
Duct Ligation ◽  
Conventional Medical Therapy ◽  
Better Than

Patients with severe, inoperable cholestasis and intractable pruritus not responding to conventional medical therapy might benefit from a depletion of their bile acid pool by sorbent perfusion since accumulated bile acids are possibly responsible for their itching. In vitro, USP-charcoal-coated glass beads removed bile acids from human plasma far better than any other sorbent tested. In order to demonstrate the safety and efficacy of charcoal plasmaperfusion in vivo, five dogs underwent plasmapheresis one week following cholecystectomy and bile duct ligation, and 2.2 ± 0.2 (x̄ ± SD) times their plasma volume was passed over a column containing 400 ml of charcoal-coated glass beads prior to reinfusion. During the procedure the plasma bile acid concentration was reduced by 40.2 ± 4.0% and the bilirubin level by 48.2 ± 3.3%. The columns, whose capacity was far from being saturated, retained 1.3 ± 0.4 times the pre-perfusion plasma pool of bile acids (1.1 ± 0.2 for bilirubin) suggesting that substantial amounts of bile acids and bilirubin were mobilized from tissue stores. The procedure was well tolerated by the animals and might have promising clinical applications.

scholarly journals Bile acid N-acetylglucosaminidation. In vivo and in vitro evidence for a selective conjugation reaction of 7 beta-hydroxylated bile acids in humans.

1992 ◽  
Vol 89 (6) ◽  
pp. 1981-1987 ◽  
Author(s):  
H U Marschall ◽  
H Matern ◽  
H Wietholtz ◽  
B Egestad ◽  
S Matern ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids

scholarly journals Amylase-Producing Myeloma Cells Reduced Sensitivity to Dexamethasone and Bortezomib.

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5690-5690
Author(s):  
Shohei Mizuno ◽  
Ichiro Hanamura ◽  
Akinobu Ota ◽  
Karnan Sivasundaram ◽  
Tomoko Narita ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Conflicts Of Interest ◽  
Constitutive Expression ◽  
Proliferation Rate ◽  
Specific Gene ◽  
Significant Difference ◽  
Mock Control ◽  
The Impact

Abstract Despite recent progress in treatment for multiple myeloma (MM), a complete cure remains elusive. To further improve the therapeutic outcome of patients with MM, elucidation of the pathology of refractory cases is important. Hyperamylasemia, which is associated with ectopic amylase (AMY) production by MM cells, is a rare condition, and it has been reported to present with poor prognosis showing rapid tumor growth, extramedullary tumor mass formation, and refractoriness of the condition. However, to date, there have been no biological analyses of MM cells ectopically producing AMY. In this study we generated transfectants that stably expressed AMY with human MM cells, and investigated the impact that ectopic AMY production has on tumor proliferation and changes in drug susceptibility in vitro and in vivo. Two human MM cell lines (RPMI8226 and KMS11) and the cDNA encoding AMY1 were used to establish transfectants with ViraPower™ Lentiviral Gateway Expression Kit (Invitrogen), because the increased AMY isotype was salivary type, which is coded in AMY1, in all MM patients previously reported. The constitutive expression and production of AMY1 were confirmed in the AMY-transfectants (8226/AMY and KMS11/AMY), while they were not in the mock controls. These transfectants were assayed for proliferation and apoptosis after exposure to dexamethasone (Dex), bortezomib (Bz) and lenalidomide (Len) in vitro. The anti-myeloma activity of Bz was also tested in vivo in a xenograft model generated by injecting 8226/AMY or the mock cells into NOD-SCID mice. 8226/AMY had no growth advantage in vitro but grew rapidly when subcutaneously transplanted in mice compared with the mock control (2,177±878 vs 970±131 mm3, p = 0.044). 8226/AMY showed a higher cell proliferation rate than the mock control in vitro when treated with Dex (40uM), Bz (2nM), and Len (1mM). The number of apoptotic 8226/AMY cells decreased after exposure to Bz and Len, but the number after exposure to Dex was equivalent compared with the mock control by the Annexin / Propidium Iodide assay. Therefore, 8226/AMY became less sensitive to Bz and Len partly through the inhibition of apoptosis induced by these drugs. 8226/AMY grew rapidly subcutaneously in mice compared with the mock control when treated with Bz (0.3mg/kg, twice weekly) (p = 0.017). As for KMS11/AMY, the AMY-transfectant showed a higher proliferation rate than the mock control in vitro. KMS11/AMY showed reduced susceptibility to Dex, no change in the susceptibility to Bz, and an enhanced susceptibility to Len unexpectedly in comparison with the mock control. The reason for a difference in the effect of ectopic AMY expression on the susceptibility to anti-MM drugs between 8226/AMY and KMS11/AMY is unclear; however, it might be due to the nature of their parental cells. No significant difference was observed in the gene expression profiling between both AMY-transfectants and each of the respective mock controls, except for AMY1, suggesting that ectopic AMY expression did not affect the expression level of the specific gene in MM. In conclusion, we found that 8226/AMY had reduced susceptibility to Dex, Bz, and Len in vitro and also rapid tumor growth with a weakened anti-tumor effect of Bz in vivo. All of these were consistent with the clinical course of previously reported patients with ectopic AMY-producing MM. On the other hand, KMS11/AMY showed an enhanced susceptibility to Len compared with the mock control, indicating that Len might be effective for some patients with AMY-producing MM. Our data provided beneficial clues for elucidating the molecular pathology and developing a treatment strategy for this clinical setting. Disclosures No relevant conflicts of interest to declare.

scholarly journals A model screening pipeline for bile acid converting anti-Clostridioides difficile bacteria reveals unique biotherapeutic potential of Peptacetobacter hiranonis

2021 ◽  
Author(s):  
Akhil A. Vinithakumari ◽  
Belen G. Hernandez ◽  
Sudeep Ghimire ◽  
Seidu Adams ◽  
Caroline Stokes ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Fecal Microbiota Transplantation ◽  
Bile Acid Metabolism ◽  
In Vitro Tests ◽  
Essential Information ◽  
Clostridioides Difficile ◽  
Gut Colonization

Clostridioides difficile is an antibiotic-resistant bacterium that causes serious, toxin-mediated enteric disease in humans and animals. Gut dysbiosis and resultant alterations in the intestinal bile acid profile play an important role in the pathogenesis of C. difficile infection (CDI). Restoration of the gut microbiota and re-establishment of bacterial bile acid metabolism using fecal microbiota transplantation (FMT) has been established as a promising strategy against this disease, although this method has several limitations. Thus, a more defined and precise microbiota-based approach using bacteria that biotransform primary bile acids into secondary bile acids could effectively overcome these limitations and control CDI. Therefore, a screening pipeline was developed to isolate bile acid converting bacteria from fecal samples. Dogs were selected as a model CDI-resistant microbiota donor for this pipeline, which yielded a novel Peptacetobacter hiranonis strain that possesses unique anti-C. difficile properties, and both bile acid deconjugation and 7-α dehydroxylating activities to perform bile acid conversion. The screening pipeline included a set of in vitro tests along with a precision in vivo gut colonization and bile acid conversion test using altered Schadler flora (ASF) colonized mice. In addition, this pipeline also provided essential information on the growth requirements for screening and cultivating the candidate bacterium, its survival in a CDI predisposing environment, and potential pathogenicity. The model pipeline documented here yielded multiple bile acid converting bacteria, including a P. hiranonis isolate with unique anti-C. difficile biotherapeutic potential, which can be further tested in subsequent preclinical and human clinical trials.

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