scholarly journals 29. Rapid Restoration of Bile Acid Compositions After Treatment with Investigational Microbiota-based Therapeutic RBX2660 for Recurrent clostrioides Difficile Infection

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S15-S16
Author(s):  
Nicky Ferdyan ◽  
Romeo Papazyan ◽  
Dana Walsh ◽  
Sarah Klein ◽  
Steve Qi ◽  
...  
Keyword(s):  
Bile Acid ◽  
Lithocholic Acid ◽  
Recurrence Risk ◽  
Intestinal Microbiome ◽  
Phase 2 Trial ◽  
Liquid Chromatography Tandem Mass ◽  
Rapid Restoration ◽  
Stool Samples ◽  
Double Blinded ◽  
To Receive

Abstract Background Recurrent Clostrioides difficile infection (rCDI) is a public health threat associated with intestinal microbiome disruption (dysbiosis), which is postulated to increase CDI recurrence risk via disruption of bile acid(BA)-mediated resistance to C. difficile colonization. RBX2660 is an investigational microbiota-based therapeutic in clinical development for reducing rCDI recurrence. Herein, we assessed BA composition among participants in a Phase 2 trial of RBX2660 for rCDI. Methods In a double-blinded trial (PUNCH CD2), rCDI participants were randomized to receive RBX2660 or placebo. Primary efficacy was defined as absence of CDI recurrence at 8 weeks after the last study treatment. Participants were asked to provide stool samples before (baseline) and up to 24 months after treatment. A liquid chromatography tandem mass spectrometry method was developed to extract and quantify 36 BAs from a total of 167 participant stool samples from 47 participants. Participant-matched samples at baseline and 1, 4, and 8 weeks were compared with a linear mixed effects model. Results Primary BAs predominated at baseline but were significantly reduced (p< .02) as early as 1 week after treatment and remained so to 24 months. Concurrently, secondary BAs, most notably deoxycholic acid (DCA) and lithocholic acid (LCA), were significantly increased (p< .01) after treatment and remained so throughout. Moreover, increases in DCA and LCA were associated with treatment response (p=.05 and p< .01, respectively), recognizing the limited sample size of treatment failures. Observed BA changes coincided with changes in taxonomic compositions—a shift from Gammaproteobacteria and Bacilli predominance before treatment to Clostridia and Bacteroidia predominance after treatment. Figure 1: BA restoration of successfully-treated participants Conclusion In a trial of RBX2660 for rCDI, participant BA compositions significantly changed from before to after treatment, remained so for at least two years, and correlated with treatment outcome. The resulting predominance of secondary BAs coincided with microbiome compositional changes. Because secondary BA are thought to repress C. difficile colonization, these changes may partly explain how RBX2660 reduced CDI recurrence. Continued evaluation of RBX2660 for rCDI is underway. Disclosures Romeo Papazyan, PhD, Ferring Pharmaceuticals (Employee) Dana Walsh, PhD, Rebiotix Inc. (Employee) Steve Qi, PhD, Ferring Pharmaceuticals (Employee) Ken Blount, PhD, Rebiotix Inc. (Employee) Karthik Srinivasan, PhD, Ferring Pharmaceuticals (Employee) Bryan Fuchs, PhD, Ferring Pharmaceuticals (Employee)

scholarly journals Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment in a randomized trial of preterm infants

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jordan T. Russell ◽  
J. Lauren Ruoss ◽  
Diomel de la Cruz ◽  
Nan Li ◽  
Catalina Bazacliu ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Gut Microbiome ◽  
Antibiotic Use ◽  
Intestinal Microbiome ◽  
Preterm Neonates ◽  
Gamma Aminobutyric Acid ◽  
Microbiome Diversity ◽  
Infant Gut Microbiome ◽  
Stool Samples ◽  
To Receive

AbstractAntibiotic use in neonates can have detrimental effects on the developing gut microbiome, increasing the risk of morbidity. A majority of preterm neonates receive antibiotics after birth without clear evidence to guide this practice. Here microbiome, metabolomic, and immune marker results from the routine early antibiotic use in symptomatic preterm Neonates (REASON) study are presented. The REASON study is the first trial to randomize symptomatic preterm neonates to receive or not receive antibiotics in the first 48 h after birth. Using 16S rRNA sequencing of stool samples collected longitudinally for 91 neonates, the effect of such antibiotic use on microbiome diversity is assessed. The results illustrate that type of nutrition shapes the early infant gut microbiome. By integrating data for the gut microbiome, stool metabolites, stool immune markers, and inferred metabolic pathways, an association was discovered between Veillonella and the neurotransmitter gamma-aminobutyric acid (GABA). These results suggest early antibiotic use may impact the gut-brain axis with the potential for consequences in early life development, a finding that needs to be validated in a larger cohort.Trial Registration This project is registered at clinicaltrials.gov under the name “Antibiotic ‘Dysbiosis’ in Preterm Infants” with trial number NCT02784821.

scholarly journals Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment: a randomized trial of preterm infants

2020 ◽  
Author(s):  
Jordan T. Russell ◽  
J. Lauren Ruoss ◽  
Diomel de la Cruz ◽  
Nan Li ◽  
Catalina Bazacliu ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Antibiotic Use ◽  
Intestinal Microbiome ◽  
Preterm Neonates ◽  
Gamma Aminobutyric Acid ◽  
Immune Markers ◽  
Microbiome Diversity ◽  
Infant Gut Microbiome ◽  
Stool Samples ◽  
To Receive

AbstractAntibiotic use in neonates can have detrimental effects on the developing gut microbiome, increasing the risk of morbidity. A majority of preterm neonates receive antibiotics after birth without clear evidence to guide this practice. Here microbiome, metabolomic, and immune marker results from the Routine Early Antibiotic use in SymptOmatic preterm Neonates (REASON) study are presented. The REASON study is the first trial to randomize symptomatic preterm neonates to receive or not receive antibiotics in the first 48 hours after birth. Using 16S rRNA sequencing of stool samples collected longitudinally for 91 neonates, the effect of such antibiotic use on microbiome diversity is assessed. The results illustrate that type of nutrition shapes the early infant gut microbiome. By integrating data for the gut microbiome, stool metabolites, stool immune markers, and inferred metabolic pathways, an association was discovered between Veillonella and the neurotransmitter gamma-aminobutyric acid (GABA). These results suggest early antibiotic use may impact the gut-brain axis with the potential for consequences in early life development, a finding that needs to be validated in a larger cohort.

scholarly journals Association of Gut Microbiota and Metabolites With Disease Progression in Children With Biliary Atresia

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Song ◽  
Li-Ying Sun ◽  
Zhi-Jun Zhu ◽  
Lin Wei ◽  
Wei Qu ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Biliary Atresia ◽  
Disease Progression ◽  
Lithocholic Acid ◽  
Early Stage ◽  
Intestinal Microbiome ◽  
Metagenomic Sequencing ◽  
Clinical Indicators ◽  
Microbiota Structure

Background and AimsBiliary atresia is the most common cause of liver disease and liver transplantation in children. The accumulation of bile acids in hepatocytes and the stimulation of the intestinal microbiome can aggravate the disease progression. This study investigated changes in the composition of the gut microbiota and its metabolites in biliary atresia and the possible effects of these changes on disease progression.MethodsStool samples of biliary atresia at different disease stages and matched control individuals were collected (early stage: 16 patients, 16 controls; later stage: 16 patients, 10 controls). Metagenomic sequencing was performed to evaluate the gut microbiota structure. Untargeted metabolomics was performed to detect and analyze the metabolites and bile acid composition.ResultsA disturbed gut microbiota structure occurred in the early and later stages of biliary atresia. Klebsiella, Streptococcus, Veillonella, and Enterococcus have always been dominant. The abundance of V. atypica displayed significant changes between the early and later stages of biliary atresia. Combined with clinical indicators, Spearman’s analysis showed that Klebsiella and Veillonella atypica strongly correlated with liver enzymes. Enterococcus faecium had an enormously positive relationship with lithocholic acid derivatives. Metabolites involved in tryptophan metabolism were changed in the patients with biliary atresia, which had a significant association with stool V. atypica and blood total bilirubin (p < 0.05).ConclusionsThe liver damage of biliary atresia was directly or indirectly exacerbated by the interaction of enriched Klebsiella (K. pneumoniae), Veillonella (V. atypica), and Enterococcus (E. faecium) with dysmetabolism of tryptophan and bile acid.

Pharmacological effects of secondary bile acid microparticles in diabetic murine model

2020 ◽  
Vol 16 ◽  
Author(s):  
Armin Mooranian ◽  
Nassim Zamani ◽  
Bozica Kovacevic ◽  
Corina Mihaela Ionescu ◽  
Giuseppe Luna ◽  
...  
Keyword(s):  
Bile Acid ◽  
Blood Glucose ◽  
Bile Acids ◽  
Lithocholic Acid ◽  
Diabetes Treatment ◽  
Secondary Bile Acid ◽  
Glucose Levels ◽  
Anti Inflammatory ◽  
Antidiabetic Effects

Aim: Examine bile acids effects in Type 2 diabetes. Background: In recent studies, the bile acid ursodeoxycholic acid (UDCA) has shown potent anti-inflammatory effects in obese patients while in type 2 diabetics (T2D) levels of the pro-inflammatory bile acid lithocholic acid were increased, and levels of the anti-inflammatory bile acid chenodeoxycholic acid were decreased, in plasma. Objective: Hence, this study aimed to examine applications of novel UDCA nanoparticles in diabetes. Methods: Diabetic balb/c adult mice were divided into three equal groups and gavaged daily with either empty microcapsules, free UDCA, or microencapsulated UDCA over two weeks. Their blood, tissues, urine, and faeces were collected for blood glucose, inflammation, and bile acid analyses. UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Results: UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Conclusion: Bile acids modulated the bile profile without affecting blood glucose levels.

Fecal Microbiome and Bile Acid Metabolome in Adult Short Bowel Syndrome

2021 ◽  
Author(s):  
Harold J. Boutte ◽  
Jacqueline Chen ◽  
Todd N. Wylie ◽  
Kristine M. Wylie ◽  
Yan Xie ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Short Bowel Syndrome ◽  
Lithocholic Acid ◽  
Intestinal Failure ◽  
Patient Specific ◽  
Rrna Gene ◽  
Healthy Controls ◽  
Fecal Microbiome ◽  
Short Bowel

Background & Aims: Loss of functional small bowel surface area causes short bowel syndrome (SBS), intestinal failure, and parenteral nutrition (PN) dependence. The gut adaptive response following resection may be difficult to predict, and it may take up to two years to determine which patients will wean from PN. Here we examined features of gut microbiota and bile acid (BA) metabolism in determining adaptation and ability to wean from PN. Methods: Stool and sera were collected from healthy controls and from SBS patients (n=52) with ileostomy, jejunostomy, ileocolonic and jejunocolonic anastomoses fed with PN plus enteral nutrition or who were exclusively enterally fed. We undertook 16S rRNA gene sequencing, BA profiling and 7α-hydroxy-4-cholesten-3-one (C4) quantitation with LC-MS/MS, and serum amino acid analyses. Results: SBS patients exhibited altered gut microbiota with reduced gut microbial diversity compared to healthy controls. We observed differences in the microbiomes of SBS patients with ileostomy vs. jejunostomy, jejunocolonic vs. ileocolonic anastomoses, and PN-dependence compared to those who weaned from PN. Stool and serum BA composition and C4 concentrations were also altered in SBS patients, reflecting adaptive changes in enterohepatic BA cycling. Stools from patients who weaned from PN were enriched in secondary BAs including deoxycholic acid and lithocholic acid. Conclusions: Shifts in gut microbiota and BA metabolites may generate a favorable luminal environment in select SBS patients, promoting the ability to wean from PN. Pro-adaptive microbial species and select BA may provide novel targets for patient-specific therapies for SBS.

Comparison of stent related symptoms in patients taking mirabegron, solifenacin, or tamsulosin: A double blinded randomized clinical trial

2021 ◽  
pp. 039156032110481
Author(s):  
Abhishek Chandna ◽  
Santosh Kumar ◽  
Kalpesh M Parmar ◽  
Aditya P Sharma ◽  
Sudheer K Devana ◽  
...  
Keyword(s):  
General Health ◽  
Bodily Pain ◽  
Ureteroscopic Lithotripsy ◽  
Health Indices ◽  
Pain Scores ◽  
Robotic Pyeloplasty ◽  
Group A ◽  
Group B ◽  
Double Blinded ◽  
To Receive

Background: The present study aims to assess the efficacy of mirabegron, a novel beta-3 agonist for ameliorating stent related symptoms (SRSs) as compared to tamsulosin and solifenacin. Methods: Total of 150 patients undergoing ureteral stent placement following ureteroscopic lithotripsy, percutaneous nephrolithotomy, or laparoscopic/robotic pyeloplasty were randomized in 1:1:1 fashion to receive mirabegron 50 mg (group A), solifenacin 5 mg (group B), and tamsulosin 0.4 mg (group C) OD respectively. Patients were followed at POD10 (I visit), 4 weeks (II visit) after surgery, and 2 weeks post-stent removal. Validated vernacular version of ureteric stent symptoms questionnaire (USSQ) was administered to the patients at each visit. Results: Out of 150 patients randomized, 123 patients (A; n = 41, B; n = 40, and C; n = 42) completed the study. The groups were comparable in terms of urinary index score of USSQ at I and II visits ( p = 0.119 and 0.076, respectively). A lower proportion of patients in group B experiencing bodily pain at II visit ( p = 0.039), however, pain scores were comparable. Significantly lower general health index scores were observed in group A at I visit and over 4 weeks ( p = 0.007). No significant differences were observed in other domains of USSQ. Age, sex, and surgical procedure undertaken did not significantly impact the scores in various USSQ domains. Conclusion: Mirabegron demonstrates comparable benefit in alleviating SRSs with better general health indices and may be an effective alternative for SRSs, especially when tamsulosin or solifenacin are contra-indicated or poorly tolerated.

scholarly journals LAPAROSCOPIC CHOLECYSTECTOMY;

2013 ◽  
Vol 20 (05) ◽  
pp. 699-706
Author(s):  
HEMMATPOOR BEHZAD ◽  
MAHVAR TAYEBEH ◽  
MAKHSOSI BEHNAM REZA ◽  
Saeb Morteza
Keyword(s):  
Laparoscopic Cholecystectomy ◽  
Shoulder Pain ◽  
Rating Scale ◽  
Controlled Study ◽  
P Value ◽  
Medical Sciences ◽  
Preoperative Administration ◽  
Elective Laparoscopic Cholecystectomy ◽  
Double Blinded ◽  
To Receive

Background: shoulder pain after laparoscopic procedure is a frequent complication encountered in surgery ward. Severaltreatments have been proposed to reduce it. This study aimed to evaluate the efficacy of preoperative administration of gabapentin inpreventing and attenuating Post Laparoscpoic Shoulder Pain (PLSP) after laparoscopic cholecystectomy. Design: In a randomised,double blinded placebo controlled study. Setting: Woman's Hospital, Kermanshah University of Medical Sciences. Period: April 2011 toMarch 2012. Material and methods: 90 patients of ASA physical status I-II undergoing elective laparoscopic cholecystectomy wererandomly allocated to receive gabapentin 600 mg or placebo ,half an hour before surgery. The presence analgesia and side effects wererecorded for 12h postoperatively in same times. Results: Incidence Verbal Rating Scale (VRS) ≥ 4 at different times after arrival to PACUwere significantly lower in gabapentin group in arrival (P Value= 0.003) and then after 30 miniute (P Value= 0.02) and 2 (P Value=0.003), 4 (P Value= 0.03) and 6 (P Value= 0.04) hours after arrival to Post Anesthesia Care Unit (PACU). But this sigificancy lost at 12hours (P Value= 0.07) after arrival to PACU. Also there was a reduction in amounts of postoperative in ward analgesic consumption. Sideeffects were not different between two groups. Conclusions: 600 mg gabapentin as premedication is effective and safe for reducing postlaparoscopicshoulder pain intensity after general laparoscopy compared with placebo.

scholarly journals Effects of clofibrate on some microsomal hydroxylations involved in the formation and metabolism of bile acids in rat liver

1976 ◽  
Vol 156 (2) ◽  
pp. 445-448 ◽  
Author(s):  
B O Angelin ◽  
I Björkhem ◽  
K Einarsson
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Rat Liver ◽  
Lithocholic Acid ◽  
Present Knowledge ◽  
Acid Formation ◽  
Microsomal Metabolism ◽  
Endogenous Cholesterol

1. The liver microsomal metabolism of [4-14C]cholesterol, endogenous cholesterol, 7 α-hydroxy-4-[6 β-3H]cholesten-3-one, 5-β-[7 β-3H]cholestane-3 α, 7 α-diol and [3H]lithocholic acid was studdied in control and clofibrate (ethyl p-chlorophenoxyisobutyrate)-treated rats. 2. The extent of 7 α-hydroxylation of exogenous [414C]cholesterol and endogenous cholesterol, the latter determined with a mass fragmentographic technique, was the same in the two groups of rats. The extent of 12 α-hydroxylation of 7 α-hydroxy-4-cholesten-3-one and 5 β-cholestane-3 α, 7 α-diol was increased by about 60 and 120% respectively by clofibrate treatment. The 26-hydroxylation of 5 β-cholestane-3 α, 7 α-diol was not significantly affected by clofibrate. The 6 β-hydroxylation of lithocholic acid was about 80% higher in the clofibrate-treated animals than in the controls. 3. The results are discussed in the context of present knowledge about the liver microsomal hydroxylating system and bile acid formation in patients with hypercholesterolaemia, treated with clofibrate.

Self-assembled Supramolecular Nanomicelles from Bile Acid-Docetaxel Conjugate are Highly Tolerable with Improved Therapeutic Efficacy

2021 ◽  
Author(s):  
Vedagopuram Sreekanth ◽  
Sanjay Pal ◽  
Sandeep Kumar ◽  
Varsha Komalla ◽  
Poonam Yadav ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Bile Acid ◽  
Therapeutic Efficacy ◽  
Lithocholic Acid ◽  
Self Assembled

Herein, we present the engineering of a supramolecular nanomicellar system that is composed of self-assembled units of PEGylated lithocholic acid (LCA)-Docetaxel (DTX) conjugate (LCA-DTX-PEG). We tethered a short polyethylene glycol...

Low-Dose Aspirin for the Prevention and Treatment of Preeclampsia

2021 ◽  
pp. 7-12
Author(s):  
Danielle M. Panelli ◽  
Deirdre J. Lyell
Keyword(s):  
Lower Risk ◽  
Low Dose ◽  
Controlled Trial ◽  
Entire Cohort ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Prevention And Treatment ◽  
Double Blinded ◽  
The Impact ◽  
To Receive

“CLASP: A Randomized Trial of Low-Dose Aspirin for the Prevention and Treatment of Preeclampsia Among 9364 Pregnant Women” was a double-blinded, placebo-controlled trial that evaluated the impact of antenatal aspirin administration on development of preeclampsia and intrauterine growth restriction (IUGR). A total of 9364 women either at risk for preeclampsia or currently experiencing preeclampsia or IUGR were enrolled between 12 and 32 weeks and randomized to receive 60mg aspirin daily or placebo. While a nonsignificant 12% reduction in the odds of preeclampsia was found among the entire cohort, the reduction in preeclampsia with aspirin use was more pronounced for those who began prophylaxis prior to 20 weeks (22% reduction, p = 0.06). There was also a lower risk of preterm birth before 37 weeks in those who received aspirin at any time (19.7% vs. 22.2%, p = 0.003) but no difference in IUGR infants. In conclusion, 60mg aspirin daily did not significantly reduce the risk of preeclampsia or IUGR among the women included in this study.

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