Investigating the role of the gastrointestinal microbiome in response to immune checkpoint inhibitors (ICIs) among patients (pts) with metastatic renal cell carcinoma (mRCC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 730-730 ◽  
Author(s):  
Anika Agarwal ◽  
Jennifer Modliszewski ◽  
Lauren Davey ◽  
Marco Reyes-Martinez ◽  
Daniella Runyambo ◽  
...  
Keyword(s):  
Beta Diversity ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Alpha Diversity ◽  
Diversity Indices ◽  
P Value ◽  
Diversity Analysis ◽  
Microbial Composition ◽  
Response Factors ◽  
Microbial Dna

730 Background: ICIs are effective in mRCC, but one pertinent clinical need is to identify predictive biomarkers for response. The PD-1 receptor has been implicated in regulating gastrointestinal commensal bacteria, with varied immune interactions, thereby impacting response to ICIs. We evaluated bacterial taxa and ICI outcomes in mRCC pts. Methods: Fecal samples from 22 mRCC pts were collected at baseline, week (wk)-4 on ICI, and upon disease progression. Pts were grouped as responders (R, complete or partial response) or non-responders (NR, stable or progressive disease). Microbial DNA was isolated by next generation DNA sequencing. The V4 region of bacterial 16S ribosomal RNA was amplified from extracted DNA and analyzed for bacterial abundance, as well as alpha diversity indices (number of amplicon sequence variants [ASVs], Shannon’s Index, Faith’s Phylogenetic Diversity, and Pielou’s evenness) and beta diversity indices on ASVs (Bray-Curtis, Jaccard, and unweighted/weighted UniFrac dissimilarity measures). Results: Beta diversity analysis at baseline showed no difference in microbial composition between Rs and NRs. However, beta diversity analysis did show a significant change in composition from baseline to wk 4 in R vs NR pts (Bray Curtis p-value=0.03). Among mRCC pts with CR to ICIs, counts of bacteria in the phylum Verrucomicrobia had an upward trend from baseline to wk 4. All mRCC pts with CR (n=3) had Akkermansia at wk 4. However, Akkermansia colonization was not sufficient for response, present in 7/9 Rs and 6/11 NRs. Conclusions: Baseline microbiome differences between ICI Rs and NRs are not enough to predict outcomes. Diversity changes between baseline and wk-4 on treatment could be an early predictor of response. Factors other than presence of Akkermansia (tumor or host-specific, Akkermansia strain variation, or other bacteria in the microenvironment) may contribute to response. Further species and strain-level profiling of the microbiota, tumor-specific genomic alterations, host immune response, and increasing sample size of ICI-treated patients may improve detection of significant differences between Rs and NRs.

scholarly journals Microbiota Changes in Fathers Consuming a High Prebiotic Fiber Diet Have Minimal Effects on Male and Female Offspring in Rats

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 820
Author(s):  
Faye Chleilat ◽  
Alana Schick ◽  
Raylene A. Reimer
Keyword(s):  
Beta Diversity ◽  
Control Diet ◽  
Gastrointestinal Hormones ◽  
Alpha Diversity ◽  
Female Offspring ◽  
Sprague Dawley ◽  
Microbial Composition ◽  
Gut Hormone ◽  
Satiety Hormone ◽  
Prebiotic Fiber

Background: Consuming a diet high in prebiotic fiber has been associated with improved metabolic and gut microbial parameters intergenerationally, although studies have been limited to maternal intake with no studies examining this effect in a paternal model. Method: Male Sprague Dawley rats were allocated to either (1) control or (2) oligofructose-supplemented diet for nine weeks and then mated. Offspring consumed control diet until 16 weeks of age. Bodyweight, body composition, glycemia, hepatic triglycerides, gastrointestinal hormones, and gut microbiota composition were measured in fathers and offspring. Results: Paternal energy intake was reduced, while satiety inducing peptide tyrosine tyrosine (PYY) gut hormone was increased in prebiotic versus control fathers. Increased serum PYY persisted in female prebiotic adult offspring. Hepatic triglycerides were decreased in prebiotic fathers with a similar trend (p = 0.07) seen in female offspring. Gut microbial composition showed significantly reduced alpha diversity in prebiotic fathers at 9 and 12 weeks of age (p < 0.001), as well as concurrent differences in beta diversity (p < 0.001), characterized by differences in Bifidobacteriaceae, Lactobacillaceae and Erysipelotrichaceae, and particularly Bifidobacterium animalis. Female prebiotic offspring had higher alpha diversity at 3 and 9 weeks of age (p < 0.002) and differences in beta diversity at 15 weeks of age (p = 0.04). Increases in Bacteroidetes in female offspring and Christensenellaceae in male offspring were seen at nine weeks of age. Conclusions: Although paternal prebiotic intake before conception improves metabolic and microbiota outcomes in fathers, effects on offspring were limited with increased serum satiety hormone levels and changes to only select gut bacteria.

scholarly journals Gut Microbiome in Psoriasis: An Updated Review

Pathogens ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 463
Author(s):  
Mariusz Sikora ◽  
Albert Stec ◽  
Magdalena Chrabaszcz ◽  
Aleksandra Knot ◽  
Anna Waskiel-Burnat ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Beta Diversity ◽  
Large Scale ◽  
Skin Diseases ◽  
Intestinal Barrier ◽  
Alpha Diversity ◽  
Current Data ◽  
Intestinal Microbiome ◽  
Microbial Composition ◽  
Alpha And Beta Diversity

(1) Background: A growing body of evidence highlights that intestinal dysbiosis is associated with the development of psoriasis. The gut–skin axis is the novel concept of the interaction between skin diseases and microbiome through inflammatory mediators, metabolites and the intestinal barrier. The objective of this study was to synthesize current data on the gut microbial composition in psoriasis. (2) Methods: We conducted a systematic review of studies investigating intestinal microbiome in psoriasis, using the PRISMA checklist. We searched MEDLINE, EMBASE, and Web of Science databases for relevant published articles (2000–2020). (3) Results: All of the 10 retrieved studies reported alterations in the gut microbiome in patients with psoriasis. Eight studies assessed alpha- and beta-diversity. Four of them reported a lack of change in alpha-diversity, but all confirmed significant changes in beta-diversity. At the phylum-level, at least two or more studies reported a lower relative abundance of Bacteroidetes, and higher Firmicutes in psoriasis patients versus healthy controls. (4) Conclusions: There is a significant association between alterations in gut microbial composition and psoriasis; however, there is high heterogeneity between studies. More unified methodological standards in large-scale studies are needed to understand microbiota’s contribution to psoriasis pathogenesis and its modulation as a potential therapeutic strategy.

scholarly journals Comparison of PCR versus PCR-Free DNA Library Preparation for Characterising the Human Faecal Virome

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2093
Author(s):  
Shen-Yuan Hsieh ◽  
Mohammad A. Tariq ◽  
Andrea Telatin ◽  
Rebecca Ansorge ◽  
Evelien M. Adriaenssens ◽  
...  
Keyword(s):  
Alpha Diversity ◽  
Diversity Indices ◽  
P Value ◽  
Library Preparation ◽  
High Genetic Diversity ◽  
Sequencing Platform ◽  
Viral Genomes ◽  
Healthy Donors ◽  
Faecal Samples ◽  
Sequencing Platforms

The human intestinal microbiota is abundant in viruses, comprising mainly bacteriophages, occasionally outnumbering bacteria 10:1 and is termed the virome. Due to their high genetic diversity and the lack of suitable tools and reference databases, the virome remains poorly characterised and is often referred to as “viral dark matter”. However, the choice of sequencing platforms, read lengths and library preparation make study design challenging with respect to the virome. Here we have compared the use of PCR and PCR-free methods for sequence-library construction on the Illumina sequencing platform for characterising the human faecal virome. Viral DNA was extracted from faecal samples of three healthy donors and sequenced. Our analysis shows that most variation was reflecting the individually specific faecal virome. However, we observed differences between PCR and PCR-free library preparation that affected the recovery of low-abundance viral genomes. Using three faecal samples in this study, the PCR library preparation samples led to a loss of lower-abundance vOTUs evident in their PCR-free pairs (vOTUs 128, 6202 and 8364) and decreased the alpha-diversity indices (Chao1 p-value = 0.045 and Simpson p-value = 0.044). Thus, differences between PCR and PCR-free methods are important to consider when investigating “rare” members of the gut virome, with these biases likely negligible when investigating moderately and highly abundant viruses.

scholarly journals Diversity Indices of Plant Communities and Their Rhizosphere Microbiomes: An Attempt to Find the Connection

2021 ◽  
Vol 9 (11) ◽  
pp. 2339
Author(s):  
Aleksei O. Zverev ◽  
Arina A. Kichko ◽  
Aleksandr G. Pinaev ◽  
Nikolay A. Provorov ◽  
Evgeny E. Andronov
Keyword(s):  
Microbial Communities ◽  
Plant Communities ◽  
Plant Diversity ◽  
Beta Diversity ◽  
Mutual Influence ◽  
Plant Root ◽  
Alpha Diversity ◽  
Diversity Indices ◽  
Alpha And Beta Diversity ◽  
Highly Correlated

The rhizosphere community represents an “ecological interface” between plant and soil, providing the plant with a number of advantages. Despite close connection and mutual influence in this system, the knowledge about the connection of plant and rhizosphere diversity is still controversial. One of the most valuable factors of this uncertainty is a rough estimation of plant diversity. NGS sequencing can make the estimations of the plant community more precise than classical geobotanical methods. We investigate fallow and crop sites, which are similar in terms of environmental conditions and soil legacy, yet at the same time are significantly different in terms of plant diversity. We explored amplicons of both the plant root mass (ITS1 DNA) and the microbial communities (16S rDNA); determined alpha- and beta-diversity indices and their correlation, and performed differential abundance analysis. In the analysis, there is no correlation between the alpha-diversity indices of plants and the rhizosphere microbial communities. The beta-diversity between rhizosphere microbial communities and plant communities is highly correlated (R = 0.866, p = 0.01). ITS1 sequencing is effective for the description of plant root communities. There is a connection between rhizosphere communities and the composition of plants, but on the alpha-diversity level we found no correlation. In the future, the connection of alpha-diversities should be explored using ITS1 sequencing, even in more similar plant communities—for example, in different synusia.

scholarly journals Unimodal Relationships of Understory Alpha and Beta Diversity along Chronosequence in Coppiced and Unmanaged Beech Forests

Diversity ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 101 ◽  
Author(s):  
Sándor Bartha ◽  
Roberto Canullo ◽  
Stefano Chelli ◽  
Giandiego Campetella
Keyword(s):  
Beta Diversity ◽  
Management Practices ◽  
Multiple Scales ◽  
Forest Succession ◽  
Spatial Scales ◽  
Alpha Diversity ◽  
Structural Diversity ◽  
Diversity Indices ◽  
Alpha And Beta Diversity ◽  
Coppice Management

Patterns of diversity across spatial scales in forest successions are being overlooked, despite their importance for developing sustainable management practices. Here, we tested the recently proposed U-shaped biodiversity model of forest succession. A chronosequence of 11 stands spanning from 5 to 400 years since the last disturbance was used. Understory species presence was recorded along 200 m long transects of 20 × 20 cm quadrates. Alpha diversity (species richness, Shannon and Simpson diversity indices) and three types of beta diversity indices were assessed at multiple scales. Beta diversity was expressed by a) spatial compositional variability (number and diversity of species combinations), b) pairwise spatial turnover (between plots Sorensen, Jaccard, and Bray–Curtis dissimilarity), and c) spatial variability coefficients (CV% of alpha diversity measures). Our results supported the U-shaped model for both alpha and beta diversity. The strongest differences appeared between active and abandoned coppices. The maximum beta diversity emerged at characteristic scales of 2 m in young coppices and 10 m in later successional stages. We conclude that traditional coppice management maintains high structural diversity and heterogeneity in the understory. The similarly high beta diversities in active coppices and old-growth forests suggest the presence of microhabitats for specialist species of high conservation value.

scholarly journals Vaginal bacterial community composition and concentrations of estradiol at the time of artificial insemination in Brangus heifers

2020 ◽  
Vol 98 (6) ◽  
Author(s):  
Riley D Messman ◽  
Zully E Contreras-Correa ◽  
Henry A Paz ◽  
George Perry ◽  
Caleb O Lemley
Keyword(s):  
Bacterial Community ◽  
Community Composition ◽  
Artificial Insemination ◽  
Beta Diversity ◽  
Bacterial Community Composition ◽  
Alpha Diversity ◽  
Species Level ◽  
Rrna Gene ◽  
Microbial Composition ◽  
Vaginal Tract

Abstract The knowledge surrounding the bovine vaginal microbiota and its implications on fertility and reproductive traits remains incomplete. The objective of the current study was to characterize the bovine vaginal bacterial community and estradiol concentrations at the time of artificial insemination (AI). Brangus heifers (n = 78) underwent a 7-d Co-Synch + controlled internal drug release estrus synchronization protocol. At AI, a double-guarded uterine culture swab was used to sample the anterior vaginal tract. Immediately after swabbing the vaginal tract, blood samples were collected by coccygeal venipuncture to determine concentrations of estradiol. Heifers were retrospectively classified as pregnant (n = 29) vs. nonpregnant (n = 49) between 41 and 57 d post-AI. Additionally, heifers were classified into low (1.1 to 2.5 pg/mL; n = 21), medium (2.6 to 6.7 pg/mL; n = 30), and high (7.2 to 17.6 pg/mL; n = 27) concentration of estradiol. The vaginal bacterial community composition was determined through sequencing of the V4 region from the 16S rRNA gene using the Illumina Miseq platform. Alpha diversity was compared via ANOVA and beta diversity was compared via PERMANOVA. There were no differences in the Shannon diversity index (alpha diversity; P = 0.336) or Bray–Curtis dissimilarity (beta diversity; P = 0.744) of pregnant vs. nonpregnant heifers. Overall, bacterial community composition in heifers with high, medium, or low concentrations of estradiol did not differ (P = 0.512). While no overall compositional differences were observed, species-level differences were present within pregnancy status and estradiol concentration groups. The implications of these species-level differences are unknown, but these differences could alter the vaginal environment thereby influencing fertility and vaginal health. Therefore, species-level changes could provide better insight rather than overall microbial composition in relation to an animal’s reproductive health.

scholarly journals The Association Between Breast Density and Gut Microbiota Composition at 2 Years Post-Menarche: A Cross-Sectional Study of Adolescents in Santiago, Chile

2021 ◽  
Vol 11 ◽  
Author(s):  
Lara S. Yoon ◽  
Jonathan P. Jacobs ◽  
Jessica Hoehner ◽  
Ana Pereira ◽  
Juan Cristóbal Gana ◽  
...  
Keyword(s):  
Breast Density ◽  
Gut Microbiome ◽  
Beta Diversity ◽  
Diversity Index ◽  
Alpha Diversity ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Linear Modeling ◽  
Microbial Composition ◽  
Cross Sectional

The gut microbiome has been linked to breast cancer via immune, inflammatory, and hormonal mechanisms. We examined the relation between adolescent breast density and gut microbial composition and function in a cohort of Chilean girls. This cross-sectional study included 218 female participants in the Growth and Obesity Cohort Study who were 2 years post-menarche. We measured absolute breast fibroglandular volume (aFGV) and derived percent FGV (%FGV) using dual energy X-ray absorptiometry. All participants provided a fecal sample. The gut microbiome was characterized using 16S ribosomal RNA sequencing of the V3-V4 hypervariable region. We examined alpha diversity and beta diversity across terciles of %FGV and aFGV. We used MaAsLin2 for multivariable general linear modeling to assess differential taxa and predicted metabolic pathway abundance (MetaCyc) between %FGV and aFGV terciles. All models were adjusted for potential confounding variables and corrected for multiple comparisons. The mean %FGV and aFGV was 49.5% and 217.0 cm3, respectively, among study participants. Similar median alpha diversity levels were found across %FGV and aFGV terciles when measured by the Shannon diversity index (%FGV T1: 4.0, T2: 3.9, T3: 4.1; aFGV T1: 4.0, T2: 4.0, T3: 4.1). %FGV was associated with differences in beta diversity (R2 =0.012, p=0.02). No genera were differentially abundant when comparing %FGV nor aFGV terciles after adjusting for potential confounders (q &gt; 0.56 for all genera). We found no associations between predicted MetaCyc pathway abundance and %FGV and aFGV. Overall, breast density measured at 2 years post-menarche was not associated with composition and predicted function of the gut microbiome among adolescent Chilean girls.

scholarly journals Effect of Infection with, and Treatment of, Sensitive and Resistant Strains of Teladorsagia Circumcincta on the Ovine Intestinal Microbiota

2018 ◽  
Author(s):  
Craig A. Watkins ◽  
Dave J. Bartley ◽  
Burcu Gündüz Ergün ◽  
Büşra Yıldızhan ◽  
Tracy Ross-Watt ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Anthelmintic Resistance ◽  
Predictive Biomarkers ◽  
Alpha Diversity ◽  
Nematode Species ◽  
Microbial Composition ◽  
Experimental Conditions ◽  
Teladorsagia Circumcincta ◽  
Resistant Strains ◽  
Preliminary Study

ABSTRACTNematodes are one of the main impactors on health, welfare and productivity of farmed animals. Teladorsagia circumcincta is arguably one of the most globally important nematode species in sheep. Control of these nematode infections is essential and heavily reliant on chemotherapy (anthelmintics), but this has been complicated by the development of anthelmintic resistance. In mammals the composition of the intestinal microbiota has been shown to have a significant effect on overall health. The interactions between host, microbiota and pathogens are complex and influenced by numerous factors. In this study, the interactions between T. circumcincta infections and microbial composition and abundance were investigated. In a preliminary study the intra-and inter-individual diversity and composition of the microbiota of grazing sheep was assessed in two distinct regions of the ovine intestinal tract, the terminal ileum (TI) and rectal contents. Additionally, the effects of experimental infection of sheep with two strains of T. circumcincta (anthelmintic resistant or sensitive) on the microbiota were assessed with and without anthelmintic (monepantel) administration. The inter-animal variability was greater in the TI compared to the rectal samples. However, the alpha-diversity (species richness) was significantly lower in the TI samples. In the experimental study, clear differences were observed between successfully treated animals and those sheep that were left untreated and/or those carrying resistant nematodes. Differences in microbiota between the four different experimental conditions were observed and potential predictive biomarkers were identified. In particular, a restoration of potentially beneficial Bifidobacteria sp. in successfully-treated animals was observed.

Outcomes of patients (pts) with advanced urothelial carcinoma (aUC) treated with immune checkpoint inhibitors (ICIs): Associations with age, race, sex and smoking history.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16526-e16526
Author(s):  
Dimitrios Makrakis ◽  
Rafee Talukder ◽  
Lucia Carril ◽  
Ivan de Kouchkovsky ◽  
Joseph J Park ◽  
...  
Keyword(s):  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Smoking History ◽  
Risk Scores ◽  
P Value ◽  
Demographic Groups ◽  
Significant Difference ◽  
Clinicopathologic Factors

e16526 Background: ICIs have altered the therapeutic landscape in pts with aUC and new biomarkers are needed to better predict response and outcomes with ICIs. It is unclear whether demographics, such as race, age, sex and history of smoking, are associated with outcomes with ICIs. We hypothesized that specific demographic groups (sex, age, race, smoking history) would be associated with outcomes with ICIs in aUC. Methods: We performed a retrospective cohort study across 25 institutions. Data collected included demographic and clinicopathologic factors, response and outcomes. We calculated observed response rate (ORR), Progression-Free Survival (PFS) and overall survival (OS) for specific demographic groups. We built multivariable models (logistic regression for ORR; Cox regression for PFS and OS) with all demographic groups to assess outcomes. Analysis was done for the overall population and stratified by treatment line (first line [1L]; salvage [2+L]). The stratified analysis was also adjusted for known prognostic risk scores (internally developed for 1L; Bellmunt for 2+L); p-value < 0.05 was significant. Results: We identified 1026 pts; 754, 744 and 780 were included in OS, ORR and PFS analysis. Overall, median age at ICI initiation was 70; 26% female; 75% White, 11% Hispanic, 5% Black, 8% other; 69% had smoking history; 28% with mixed histology; 17% with upper tract UC. In the unstratified analysis, age 65-74 (vs < 65) was significantly associated with higher ORR (32% vs 22%) and median PFS (5 vs 3 mo HR 0.8); otherwise no significant difference was noted among groups for ORR, PFS, OS in both the stratified and unstratified analyses (Table). Conclusions: We did not identify significant associations between age, sex, race or smoking history and ORR, PFS, OS with ICIs in pts with aUC. Limitations include retrospective nature, lack of randomization, possible selection and confounding factors. Further research is required to identify prognostic and predictive biomarkers for ICI therapy in aUC.[Table: see text]

scholarly journals Performance comparison of different microbial DNA extraction methods on bird feces

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xian Hou ◽  
Shengkai Pan ◽  
Zhenzhen Lin ◽  
Jiliang Xu ◽  
Xiangjiang Zhan
Keyword(s):  
Dna Extraction ◽  
Relative Abundance ◽  
Alpha Diversity ◽  
Cell Lysis ◽  
Extraction Methods ◽  
Dna Integrity ◽  
Microbial Composition ◽  
Dna Yield ◽  
Dna Extraction Methods ◽  
Microbial Dna

Abstract Background As an important player during food digestion, gut microbiota has attracted much attention in diet adaptation studies in birds. Microbiota extracted from feces has been widely used as a proxy for gut microbiota. Although several methods have been developed for microbial DNA extraction, their performances in the bird feces have not been systematacially evaluated yet. Methods In this study, we applied three DNA extraction methods (Qiagen, MoBio and Bead) to extract DNA from feces of three avian dietary guilds (granivore, omnivore and carnivore), sequenced V4 region of 16S rRNA gene for each extract and evaluated the performances of DNA yield, DNA integrity, microbial composition, cell lysis capacity and alpha diversity for the three methods on each dietary guild. Results Bead method was the best on the performance of both DNA yield and DNA integrity regardless of dietary guild. In granivore, microbial relative abundance at both species and phylum levels, alpha diversity and cell lysis capacity were comparable among all methods. In omnivore, Qiagen had the best performance on alpha diversity, followed by Bead and MoBio. There were small variations on microbial relative abundance at both species and phylum levels among different extraction methods. MoBio exhibited the best performance on cell lysis capacity. In carnivore, considerable variations were found on microbial relative abundance at both species and phylum levels. Qiagen had the best performance on alpha diversity, followed by MoBio and Bead. MoBio had the highest cell lysis capacity. Conclusions DNA yield and integrity have no obvious impact on microbial composition, alpha diversity or cell lysis capacity. The microbiota results (e.g., microbial composition, cell lysis capacity, alpha diversity) obtained from different methods are comparable in granivorous avian species but not in omnivorous or carnivorous birds. Either method could be used in granivore microbiota studies. For omnivores and carnivores, we recommend Qiagen method when the research purpose is microbial diversity and MoBio when gram-positive bacteria is the research target.

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