scholarly journals Pilot Sub-Study of the Effect of Hepatitis C Cure by Glecaprevir/Pibrentasvir on the Gut Microbiome of Patients with Chronic Hepatitis C Genotypes 1 to 6 in the Mythen Study

2021 ◽  
Vol 14 (9) ◽  
pp. 931
Author(s):  
Bahtiyar Yilmaz ◽  
Lisa Ruckstuhl ◽  
Beat Müllhaupt ◽  
Lorenzo Magenta ◽  
Melanie Harrer Kuster ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Gut Microbiota ◽  
Beta Diversity ◽  
Alpha Diversity ◽  
Post Treatment ◽  
Genotype 3 ◽  
Genotype 4 ◽  
Alpha And Beta Diversity ◽  
Genotype 2 ◽  
Fresh Stool

In this small pilot sub-study, longitudinal gut microbiota composition changes, after successful treatment of hepatitis C virus (HCV) with the co-formulated glecaprevir/pibrentasvir (GLE/PIB), were analyzed before treatment (baseline) and 12 weeks post-treatment. Participating patients provided a fresh stool sample the week before their study visit, from which microbial DNA was extracted and sequenced for the 16S rRNA region in an Illumina MiSeq2 platform. Microbial and statistical analyses were conducted to determine the alpha-diversity (number of different taxa within a sample) and beta-diversity (number of overlapping taxa between samples). Stool samples from 58 patients were eligible for analysis. There were 27 patients with HCV genotype 1, 10 with genotype 2, 16 with genotype 3, and 5 with genotype 4. No statistically significant differences in gut microbiota diversity, species richness, or microbial community pattern were found at baseline and at post-treatment Week 12. Lack of statistically significant differences remained consistent in further analysis by demographic and baseline disease characteristics. Surprisingly, no statistically significant changes in alpha- and beta-diversity were seen in the microbiota after GLE/PIB treatment, though there was a trend toward less richness over time. Further investigation is needed into this unexpected outcome to better understand the role of HCV treatment and the gut microbiota.

scholarly journals Gut microbiota composition is associated with narcolepsy type 1

2020 ◽  
Vol 7 (6) ◽  
pp. e896
Author(s):  
Alexandre Lecomte ◽  
Lucie Barateau ◽  
Pedro Pereira ◽  
Lars Paulin ◽  
Petri Auvinen ◽  
...  
Keyword(s):  
Community Structure ◽  
Gut Microbiota ◽  
Bacterial Communities ◽  
Beta Diversity ◽  
Alpha Diversity ◽  
Amplicon Sequencing ◽  
Rrna Gene ◽  
Differential Abundance ◽  
Alpha And Beta Diversity

ObjectiveTo test the hypothesis that narcolepsy type 1 (NT1) is related to the gut microbiota, we compared the microbiota bacterial communities of patients with NT1 and control subjects.MethodsThirty-five patients with NT1 (51.43% women, mean age 38.29 ± 19.98 years) and 41 controls (57.14% women, mean age 36.14 ± 12.68 years) were included. Stool samples were collected, and the fecal microbiota bacterial communities were compared between patients and controls using the well-standardized 16S rRNA gene amplicon sequencing approach. We studied alpha and beta diversity and differential abundance analysis between patients and controls, and between subgroups of patients with NT1.ResultsWe found no between-group differences for alpha diversity, but we discovered in NT1 a link with NT1 disease duration. We highlighted differences in the global bacterial community structure as assessed by beta diversity metrics even after adjustments for potential confounders as body mass index (BMI), often increased in NT1. Our results revealed differential abundance of several operational taxonomic units within Bacteroidetes, Bacteroides, and Flavonifractor between patients and controls, but not after adjusting for BMI.ConclusionWe provide evidence of gut microbial community structure alterations in NT1. However, further larger and longitudinal multiomics studies are required to replicate and elucidate the relationship between the gut microbiota, immunity dysregulation and NT1.

scholarly journals COMBINED NS5A & NS5B NUCLEOTIDE INHIBITOR THERAPY FOR PATIENTS WITH CHRONIC HEPATITIS C WITH STAGE 5 CHRONIC KIDNEY DISEASE ON HEMODIALYSIS

2020 ◽  
Vol 57 (1) ◽  
pp. 39-44 ◽  
Author(s):  
Prasanta DEBNATH ◽  
Sanjay CHANDNANI ◽  
Pravin RATHI ◽  
Sujit NAIR ◽  
Vinay PAWAR ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Transient Elastography ◽  
Liver Stiffness ◽  
Post Treatment ◽  
Hcv Infection ◽  
Maintenance Hemodialysis ◽  
Hcv Rna ◽  
Genotype 3 ◽  
Open Label ◽  
Genotype 2

ABSTRACT BACKGROUND: Hepatitis C virus (HCV) infection is the most common hepatotropic viral infection affecting the patients on maintenance hemodialysis. Treatment of chronic HCV infection in stage 4 and 5 CKD includes a combination of elbasvir/grazoprevir and glecaprevir/pibrentasvir, which are not available in many countries. OBJECTIVE: Hence, we have conducted this study to look for the safety and efficacy of sofosbuvir combination therapy in this difficult to treat population. METHODS: We conducted a single-center, prospective, open-label study in which Stage 5 CKD patients on maintenance hemodialysis with HCV infection. Total of 18 patients was included. sofosbuvir with daclatasvir or ledipasvir was used according to genotype for 12 weeks. HCV RNA, genotype, transient elastography (TE) was considered for every patient. HCV RNA was quantified at 4th week, 12th week and 12 weeks post-treatment to look for sustained virologic response (SVR 12). RESULTS: Infection due to genotype 1 was seen in 12 (66.7%) patients followed by genotype 3 in 4 (22.3%) with each patient of genotype 2 and 5. The median value of HCV RNA was 2,35,000 IU/mL. On TE, all had liver stiffness of <9.4 KPa. All patients had HCV RNA of <15 IU/mL at 4th and 12th week of treatment and 12 weeks post-treatment. No significant change in hemoglobin, eGFR and liver stiffness was observed. CONCLUSION: Full dose sofosbuvir i.e. 400 mg, in combination with NS5A inhibitors daclatasvir or ledipasvir is found to be safe and effective in patients with end stage renal disease, who are on maintenance hemodialysis.

Human Milk Feeding Patterns at 6 Months of Age are a Major Determinant of Fecal Bacterial Diversity in Infants

2020 ◽  
pp. 089033442095757
Author(s):  
Kameron Y. Sugino ◽  
Tengfei Ma ◽  
Jean M. Kerver ◽  
Nigel Paneth ◽  
Sarah S. Comstock
Keyword(s):  
Gut Microbiota ◽  
Human Milk ◽  
Beta Diversity ◽  
Maternal Obesity ◽  
Alpha Diversity ◽  
Major Determinant ◽  
Cross Sectional ◽  
Alpha And Beta Diversity ◽  
Infant Diet ◽  
Milk Feeding

Background Maternal pre-pregnancy obesity and human milk feeding have been associated with altered infant gut microbiota. Research aim Determine the relationships between maternal pre-pregnancy BMI, human milk exposure, and their influence on the infant microbiota simultaneously. Methods This was a cross-sectional study of infants at 6 months of age ( N = 36), a time when many infants are fed a mixed diet of human milk and other foods. Fecal samples and participant information were collected from a subset of dyads enrolled in two related prospective cohorts (ARCHGUT and BABYGUT) in Michigan. Sequencing the V4 region of the 16S gene was used to analyze fecal bacterial samples collected from 6-month-old infants. Participants were grouped into four categories designated by their extent of human milk exposure (100%, 80%, 50%–80%, ≤ 20% human milk in the infant diet) and by maternal pre-pregnancy BMI category (normal, overweight, obese). Results Fewer participants with pre-pregnancy obesity were breastfeeding at 6 months postpartum compared to non-obese participants (35.7% and 81.8%, respectively). In univariate analyses, maternal pre-pregnancy BMI and human milk exposure were both significantly associated with alpha and beta diversity of the infant microbiota. However, in multivariate analyses, human milk exposure accounted for 20% of the variation in alpha diversity, but pre-pregnancy BMI was not significantly associated with any form of microbiota diversity. Conclusions The proportion of the infant diet that was human milk at 6 months was the major determinant of alpha and beta diversity of the infant. Maternal obesity contributes to the gut microbiota by its association with the extent of human milk feeding.

scholarly journals Substitutions at NS3 Residue 155, 156, or 168 of Hepatitis C Virus Genotypes 2 to 6 Induce Complex Patterns of Protease Inhibitor Resistance

2015 ◽  
Vol 59 (12) ◽  
pp. 7426-7436 ◽  
Author(s):  
Sanne B. Jensen ◽  
Stéphanie B. N. Serre ◽  
Daryl G. Humes ◽  
Santseharay Ramirez ◽  
Yi-Ping Li ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Fitness ◽  
Genotype 3 ◽  
Genotype 4 ◽  
Genotype 2 ◽  
Virus Genotypes ◽  
Complex Patterns ◽  
Main Determinants ◽  
The Impact

ABSTRACTVarious protease inhibitors (PIs) currently are becoming available for treatment of hepatitis C virus (HCV). For genotype 1, substitutions at NS3 protease positions 155, 156, and 168 are the main determinants of PI resistance. For other genotypes, similar substitutions were selected during PI treatment but were not characterized systematically. To elucidate the impact of key PI resistance substitutions on genotypes 2 to 6, we engineered the substitutions R155A/E/G/H/K/Q/T, A156G/S/T/V, and D/Q168A/E/G/H/N/V into HCV recombinants expressing genotype 2 to 6 proteases. We evaluated viral fitness and sensitivity to nine PIs (telaprevir, boceprevir, simeprevir, asunaprevir, vaniprevir, faldaprevir, paritaprevir, deldeprevir, and grazoprevir) in Huh7.5 cells. We found that most variants showed decreased fitness compared to that of the original viruses. Overall, R155K, A156G/S, and D/Q168A/E/H/N/V variants showed the highest fitness; however, genotype 4 position 168 variants showed strong fitness impairment. Most variants tested were resistant to several PIs. Resistance levels varied significantly depending on the specific substitution, genotype, and PI. For telaprevir and boceprevir, specific 155 and 156, but not 168, variants proved resistant. For the remaining PIs, most genotype 2, 4, 5, and 6, but not genotype 3, variants showed various resistance levels. Overall, grazoprevir (MK-5172) had the highest efficacy against original viruses and variants. This is the first comprehensive study revealing the impact of described key PI resistance substitutions on fitness and PI resistance of HCV genotypes 2 to 6. In conclusion, the studied substitutions induced resistance to a panel of clinically relevant PIs, including the newer PIs paritaprevir, deldeprevir, and grazoprevir. We discovered complex patterns of resistance, with the impact of substitutions varying from increased sensitivity to high resistance.

scholarly journals Changes in the gut microbiota during Asian particolored bat (Vespertilio sinensis) development

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9003
Author(s):  
Zhongwei Yin ◽  
Keping Sun ◽  
Aoqiang Li ◽  
Deyi Sun ◽  
Zhongle Li ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Beta Diversity ◽  
Redundancy Analysis ◽  
Transition Period ◽  
Bacterial Community Composition ◽  
Alpha Diversity ◽  
Alpha And Beta Diversity ◽  
Compositional Changes ◽  
Gut Microbial Community ◽  
Host Development

Background The gut microbiota is closely linked to host development, diet and health and is influenced by both the host and the environment. Although many studies have focused on the dynamics of the gut microbiota during development in captive animals, few studies have focused on the dynamics of the gut microbiota during development in wild animals, especially for the order Chiroptera. Methods In this study, we characterized the gut microbiota of the wild Asian particolored bat (Vespertilio sinensis) from 1 day to 6 weeks after birth. We explored the changes in their gut microbial community compositions, examined possible influencing factors, and predicted the feeding transition period. Results The gut microbiota changed during the development of V. sinensis. The alpha diversity of the bats’ gut microbiota gradually increased but did not change significantly from the 1st day to the 4th week after birth; however, the alpha diversity decreased significantly in week 5, then stabilized. The beta diversity differed slightly in weeks 4–6. In week 4, the fecal samples showed the highest diversity in bacterial community composition. Thus, we predicted that the potential feeding transition period for V. sinensis may occur during week 4. Redundancy analysis showed that age and body mass index significantly affected the compositional changes of the gut microbiota in Asian particolored bats. Conclusion The gut microbiota changed during the development of V. sinensis. We suggest that changes in the alpha and beta diversity during week 4 after birth indicate a potential feeding transition, highlighting the importance of diet in the gut microbiota during the development of V. sinensis.

scholarly journals Evaluation of the gut microbiome in association with biological signatures of inflammation in murine polytrauma and shock

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sandra A. Appiah ◽  
Christine L. Foxx ◽  
Dominik Langgartner ◽  
Annette Palmer ◽  
Cristian A. Zambrano ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Community Composition ◽  
Gut Microbiome ◽  
Beta Diversity ◽  
Microbial Community Composition ◽  
Alpha Diversity ◽  
Global Changes ◽  
Rrna Gene ◽  
Alpha And Beta Diversity ◽  
Increased Risk

AbstractSevere injuries are frequently accompanied by hemorrhagic shock and harbor an increased risk for complications. Local or systemic inflammation after trauma/hemorrhage may lead to a leaky intestinal epithelial barrier and subsequent translocation of gut microbiota, potentially worsening outcomes. To evaluate the extent with which trauma affects the gut microbiota composition, we performed a post hoc analysis of a murine model of polytrauma and hemorrhage. Four hours after injury, organs and plasma samples were collected, and the diversity and composition of the cecal microbiome were evaluated using 16S rRNA gene sequencing. Although cecal microbial alpha diversity and microbial community composition were not found to be different between experimental groups, norepinephrine support in shock animals resulted in increased alpha diversity, as indicated by higher numbers of distinct microbial features. We observed that the concentrations of proinflammatory mediators in plasma and intestinal tissue were associated with measures of microbial alpha and beta diversity and the presence of specific microbial drivers of inflammation, suggesting that the composition of the gut microbiome at the time of trauma, or shortly after trauma exposure, may play an important role in determining physiological outcomes. In conclusion, we found associations between measures of gut microbial alpha and beta diversity and the severity of systemic and local gut inflammation. Furthermore, our data suggest that four hours following injury is too early for development of global changes in the alpha diversity or community composition of the intestinal microbiome. Future investigations with increased temporal-spatial resolution are needed in order to fully elucidate the effects of trauma and shock on the gut microbiome, biological signatures of inflammation, and proximal and distal outcomes.

scholarly journals MON-022 Dissecting the Interplay Between Diet and PCOS Pathology on Gut Microbiota in a PCOS Mouse Model

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Valentina Rodriguez Paris ◽  
Nadeem O Kaakoush ◽  
Samantha M Solon-Biet ◽  
Melissa C Edwards ◽  
William L Ledger ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Beta Diversity ◽  
Polycystic Ovary ◽  
Cell Metabolism ◽  
Consensus Sequence ◽  
Alpha Diversity ◽  
Operational Taxonomic Unit ◽  
Intestinal Microbiome ◽  
Alpha And Beta Diversity

Abstract The gut microbiome has been implicated in the development of metabolic disorders such as obesity and type-2 diabetes, and more recently polycystic ovary syndrome (PCOS). PCOS is a heterogeneous disorder with reproductive, endocrine and metabolic irregularities, and clinical and animal studies have reported that PCOS causes a decrease in microbial diversity and composition. Diet is an important regulator of the gut microbiome, and a recent study identified that alterations in macronutrient balance impact gut microbial communities which correlate with different metabolic health outcomes (1). We have identified that macronutrient balance impacts the development of PCOS traits. Therefore, to investigate the interplay between macronutrient balance and a PCOS environment on the gut microbiome, we analyzed the intestinal microbiome from fecal pellets of control and DHT-induced PCOS mice exposed to 10 different diets that varied systematically in protein (P), carbohydrate (C) and fat (F) content. The amount of dietary P, C and F consumed significantly altered alpha and beta diversity of the gut microbiota of pooled control and PCOS mice (P&lt;0.0001). Alpha diversity between control and PCOS mice on the same diet did not differ significantly, and hence was only affected by diet composition. However, beta diversity was significantly altered between control and PCOS mice (P&lt;0.05). We performed DESeq2 analysis and identified an operational taxonomic unit (OTU) within Bacteroides (OTU3) to be the most differentially abundant OTU between control and PCOS mice, with a significant decrease in PCOS mice compared to controls (control: 7.88 and PCOS: 5.38; fold change = 1.464; P&lt;0.0001). The consensus sequence of Bacteroides OTU3 was found to share 99.2% similarity to Bacteroides acidifaciens. B. acidifaciens is associated with obesity with elevated levels reported to prevent the onset of obesity (2). Thus, we then investigated the influence of P, C and F on the relative abundance of Bacteroides OTU3 and revealed an association with C consumption, with increasing levels of C leading to increased levels of Bacteroides OTU3 (Carb: r= 0.22, p=0.0028, q=0.015). These findings demonstrate that diet exerts a stronger influence over the gut microbiome than PCOS pathology. However, the hyperandrogenic PCOS environment does lead to changes in gut microbiota beta diversity, with a specific decrease in an obesity-associated (2) Bacteroides species in PCOS mice that is also responsive to levels of C consumption. Reference: (1) Holmes et al., Cell Metabolism. 2017; 25(1): 140-151. (2) Yang et al., Mucosal Immunology. 2017, 10 (1), 104-116.

scholarly journals Effect of Bovine MFGM and LF in Infant Formula on Gut Microbiome and Metabolome at Four Months of Age

2021 ◽  
Author(s):  
Maciej Chichlowski ◽  
Nicholas Bokulich ◽  
Cheryl L Harris ◽  
Jennifer L Wampler ◽  
Fei Li ◽  
...  
Keyword(s):  
Infant Formula ◽  
Beta Diversity ◽  
Milk Fat ◽  
Alpha Diversity ◽  
Illumina Miseq ◽  
Rrna Gene ◽  
Term Infants ◽  
Linear Discriminant ◽  
Alpha And Beta Diversity ◽  
Metabolite Profiles

Abstract Background Milk fat globule membrane (MFGM) and lactoferrin (LF) are human milk bioactive components demonstrated to support gastrointestinal (GI) and immune development. Significantly fewer diarrhea and respiratory-associated adverse events through 18 months of age were previously reported in healthy term infants fed a cow's milk-based infant formula with added source of bovine MFGM and bovine LF through 12 months of age. Objectives To compare microbiota and metabolite profiles in a subset of study participants. Methods Stool samples were collected at Baseline (10–14 days of age) and Day 120 (MFGM + LF: 26, Control: 33). Bacterial community profiling was performed via16S rRNA gene sequencing (Illumina MiSeq) and alpha and beta diversity were analyzed (QIIME 2). Differentially abundant taxa were determined using Linear discriminant analysis effect size (LefSE) and visualized (Metacoder). Untargeted stool metabolites were analyzed (HPLC/mass spectroscopy) and expressed as the fold-change between group means (Control: MFGM + LF ratio). Results Alpha diversity increased significantly in both groups from baseline to 4 months. Subtle group differences in beta diversity were demonstrated at 4 months (Jaccard distance; R2 = 0.01, P = 0.042). Specifically, Bacteroides uniformis and Bacteroides plebeius were more abundant in the MFGM + LF group at 4 months. Metabolite profile differences for MFGM + LF vs Control included: lower fecal medium chain fatty acids, deoxycarnitine, and glycochenodeoxycholate, and some higher fecal carbohydrates and steroids (P &lt; 0.05). After applying multiple test correction, the differences in stool metabolomics were not significant. Conclusions Addition of bovine MFGM and LF in infant formula was associated with subtle differences in stool microbiome and metabolome by four months of age, including increased prevalence of Bacteroides species. Stool metabolite profiles may be consistent with altered microbial metabolism. Trial registration:  https://clinicaltrials.gov/ct2/show/NCT02274883).

scholarly journals Improvement of Gut Diversity and Composition After Direct-Acting Antivirals in Hepatitis C Virus–Infected Patients With or Without Human Immunodeficiency Virus Coinfection

2021 ◽  
Author(s):  
Natthaya Chuaypen ◽  
Thananya Jinato ◽  
Anchalee Avihingsanon ◽  
Sakkarin Chirapongsathorn ◽  
Supapon Cheevadhanarak ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Gut Microbiota ◽  
Alpha Diversity ◽  
Healthy Controls ◽  
Direct Acting Antivirals ◽  
Microbial Dysbiosis ◽  
Immunodeficiency Virus ◽  
Direct Acting

Abstract Background The influence of direct-acting antivirals (DAAs) on the composition of gut microbiota in hepatitis C virus (HCV)–infected patients with or without human immunodeficiency virus (HIV) is unclear. Methods We enrolled 62 patients with HCV monoinfection and 24 patients with HCV/HIV coinfection receiving elbasvir-grazoprevir from a clinical trial. Fecal specimens collected before treatment and 12 weeks after treatment were analyzed using amplicon-based 16S ribosomal RNA sequencing. Results Sustained virological response rates in the monoinfection and coinfection groups were similar (98.4% vs 95.8%). Pretreatment bacterial communities in the patient groups were less diverse and distinct from those of healthy controls. Compared with HCV-monoinfected patients, HCV/HIV-coinfected individuals showed comparable microbial alpha diversity but decreased Firmicutes-Bacteroidetes ratios. The improvement of microbial dysbiosis was observed in responders achieving sustained virological response across fibrosis stages but was not found in nonresponders. Responders with a low degree of fibrosis exhibited a recovery in alpha diversity to levels comparable to those in healthy controls. Reciprocal alterations of increased beneficial bacteria and reduced pathogenic bacteria were also observed in responders. Conclusions This study indicates a short-term effect of direct-acting antivirals in restoration of microbial dysbiosis. The favorable changes in gut microbiota profiles after viral eradication might contribute toward the reduction of HCV-related complications among infected individuals.

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