scholarly journals 2136

2017 ◽  
Vol 1 (S1) ◽  
pp. 57-57
Author(s):  
Muna Qayed ◽  
Dalia Arafat ◽  
Samridhi Banskota ◽  
John Horan ◽  
Edmund Waller ◽  
...  

OBJECTIVES/SPECIFIC AIMS: Aim 1: To compare microbiome diversity among patients who develop BSI post hematopoietic stem cell transplantation (HSCT) and patients without BSI. Aim 2: To compare microbiome diversity among patients who develop moderate to severe acute GVHD post HSCT and patients without GVHD. Aim 3: To describe alterations in specific bacterial orders (Enterobacteriaceae, Clostridia, and Lactobacillales) in pediatric patients undergoing HSCT. METHODS/STUDY POPULATION: Next-generation sequencing of the hypervariable V3 region of the 16s rRNA gene isolated from stool specimens collected at baseline (start of preparative regimen to transplant day), early (day 7–14 post HSCT), and late (day 21–28 post HSCT) from 46 children was performed. Microbiome diversity was assessed by the Shannon index as well as UniFrac analysis, and compared among patients with and without GVHD/BSI. Baseline bacterial diversity was compared among patients by primary diagnosis, race, timing of antibiotic introduction and method of supplemental nutrition. RESULTS/ANTICIPATED RESULTS: Median age was 9 years (range 0.5–19.2 years). There were 36 patients with hematologic malignancies. Patients with nonmalignant disease had a characteristic pattern of microbiome diversity (and microbiota order distribution) at baseline that persisted throughout the first month of transplant (p=0.004). Over all patients, there was an early and persistent drop in microbiome diversity throughout the transplant course. Early introduction of broad spectrum antibiotics (prior to transplant day) negatively impacted microbiome diversity (p=0.02). There was no difference in microbiome diversity among patients who developed BSI, when compared with patients without BSI. Similarly, we did not find an association between microbiome diversity and the development of moderate to severe acute GVHD. Ongoing analysis is examining the individual variations in microbiome at the species level, and their relation to transplant characteristics and clinical outcomes. DISCUSSION/SIGNIFICANCE OF IMPACT: In our analysis, microbiome diversity decreased during HSCT, but in contrast to published data, mainly in adult HSCT populations, we found no association between gut microbiome diversity and GVHD or BSI. There are ongoing clinical trials in children and adults using probiotics in HSCT with the aim of decreasing GVHD. Further analysis of our data at the species level may further inform the relationship between gut microbiome alterations and HSCT complications in children and guide clinical interventions.

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S22-S22
Author(s):  
Mehgan Teherani ◽  
Zoe Pratte ◽  
Samridhi Banskota ◽  
Dalia Gulick ◽  
Naima Djeddar ◽  
...  

Abstract Background In adults undergoing allogeneic hematopoietic cell transplantation (HCT), higher gut microbiome diversity is associated with reduced bloodstream infections (BSI) and improved overall survival (OS). Rifaximin prophylaxis in adult HCT helps to maintain microbiome diversity. We examine changes in microbiome in a cohort of pediatric patients undergoing HCT. Methods Patients were enrolled in an institutional biorepository (n=82) with a subset enrolled in an ongoing trial using rifaximin (n=21) between 2013–2020. All patients had HCT for a hematologic malignancy, using myeloablative conditioning. Patients in the rifaximin trial received rifaximin starting 7 days before HCT (D-7) through D+28, otherwise, no prophylactic antibiotics were used. Systemic antibiotic timing was categorized as none, early (≤ Day 0, day of HCT), and late (> D0). We performed 16s rRNA sequencing from stool for 73 subjects, at baseline (D-7), and weekly through D+28 (engraftment). Microbiome diversity was assessed by Shannon index. Results Median age was 9 years (range 1–20), 59% male, 41% Caucasian and 29% Black. There were no differences in BSI or mortality by age, sex, or race. Microbiome diversity changed significantly over time (p=0.008). Drop in diversity was most notable in patients who had early antibiotics (Mean=1.4, CI -0.15, 2.94, p=0.077). Higher diversity was seen when patients received none or late versus early antibiotics, but this was not statistically significant (Figure 1, p=0.23). Piperacillin-tazobactam was used empirically in 91% of patients. OS at 1 year was 88.5% (CI 68.4%, 96.1%) for patients with high (≥ median) D+28 diversity compared to 60% (CI 38.4%, 76.1%) for patients with low diversity (Figure 2, p=0.018) Only 1 of 21 (4.8%) in the rifaximin group developed a BSI with a gut bacterium compared to 8 of 61 (13.1%) not on rifaximin within the first 30 days (trial enrollment ongoing). Figure 1. Effect of systemic antibiotic timing on microbiome diversity over time. Figure 2. One-year overall survival of patients with high (>2.77) versus low (<2.77) diversity defined by median Shannon-Index. Conclusion We have shown a significant correlation between engraftment microbiome diversity and 1-year OS. Early antibiotic exposure was detrimental to microbiome diversity. Approaches to preserve microbiome diversity and prevent BSI are likely to improve HCT outcomes. Our ongoing trial using rifaximin will provide preliminary data regarding this approach. Disclosures All Authors: No reported disclosures


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Robert C. Kaplan ◽  
Zheng Wang ◽  
Mykhaylo Usyk ◽  
Daniela Sotres-Alvarez ◽  
Martha L. Daviglus ◽  
...  

Abstract Background Hispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment. Results Amplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA. Conclusions Our analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA.


2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S381-S381
Author(s):  
Hebert Dupont ◽  
Zhi-Dong Jiang ◽  
Ashley Alexander ◽  
Nadim Ajami ◽  
Joseph F Petrosino ◽  
...  

Abstract Background Fecal microbiota (FM) transplantation (FMT) is a highly effective treatment of recurrent C. difficile infection (rCDI). We have published data showing efficacy of fresh, frozen and lyophilized donor microbiota administered by colonoscopy. Most groups are moving toward use of frozen product given by enema and in evaluating encapsulated product for oral delivery. Methods This was a prospective, randomized study of subjects with rCDI (≥ 3 episodes) treated with encapsulated lyophilized FM 100 g given once or 100 g given on two successive days (total 200 g) vs. frozen FM product 100 g given by single retention enema, between March 2015 and February 2017. The clinical outcome was absence of CDI during the 60 days after FMT. The subjects were followed for 6 months for safety. In a subset recipients, microbiome composition by 16S rRNA gene profiling were analyzed on stools obtained pre- and day 2, 7, 14, 30, 60 and 90 days after FMT. Results A total of 54 subjects were enrolled (37/54; 69% female) with a median age of 71 years (range: 20–97). In the first 14 subjects treated, cure rates for oral capsules 100 g FM was 5/8 (63%) vs. 6/6 (100%) for those receiving 100 g frozen FM by enema (P = 0.209). In the second phase of the study cure rate for oral capsules 200 g FM was 17/18 (91%) vs. 20/21 (94%) for the subjects treated by enema by 100 g of frozen product (P = 0.782). No side effects were felt to be related to the procedure or the FMT products were recorded during 6 months follow-up. Two subjects died during follow-up between 3 and 6 months after study due to underlying medical conditions felt to be unrelated to FMT. Microbiota analysis were performed on 40 subjects of which 19/40 (48%) had received capsules. Figure showed that restoration of the intestinal microbiome diversity and Taxa began apparent by 2 days after FMT in both groups and resembled the donor product by 2 weeks with stabilization of the microbiota diversity and Taxa persisting for the 90 days of observation. Conclusion Administration of encapsulated, lyophilized FM resulted in durable restoration of intestinal microbiome diversity comparable to results seen with frozen product given by enema. Disclosures All authors: No reported disclosures.


2021 ◽  
Author(s):  
Elisabetta Piancone ◽  
Bruno Fosso ◽  
Mariangela De Robertis ◽  
Elisabetta Notario ◽  
Annarita Oranger ◽  
...  

To date there are several studies focusing on the importance of gut microbiome for human health, however the selection of a universal sampling matrix representative of the microbial biodiversity associated to the gastrointestinal (GI) tract, still represents a challenge. Here we present a study in which, through a deep metabarcoding analysis of the 16S rRNA gene, we compared two sampling matrices, feces (F) and colonic lavage liquid (LL), in order to evaluate their accuracy to represent the complexity of the human gut microbiome. A training set of 37 volunteers was attained and paired F and LL samples were collected from each subject. A preliminary absolute quantification of total 16S rDNA, performed by droplet digital PCR (ddPCR), confirmed that sequencing and taxonomic analysis were performed on same total bacterial abundance obtained from the two sampling methods. The taxonomic analysis of paired samples revealed that, although specific taxa were predominantly or exclusively observed in LL samples, as well as other taxa were detectable only or were predominant in stool, the microbiomes of the paired samples F and LL in the same subject hold overlapping taxonomic composition. Moreover, LL samples revealed a higher biodiversity than stool at all taxonomic ranks, as demonstrated by the Shannon Index and the Inverse Simpson's Index. We also found greater inter-individual variability than intra-individual variability in both sample matrices. Finally, functional differences were unveiled in the gut microbiome detected in the F and LL samples. A significant overrepresentation of 22 and 13 metabolic pathways, mainly occurring in Firmicutes and Proteobacteria, was observed in gut microbiota detected in feces and LL samples, respectively. This suggests that LL samples may allow for the detection of microbes adhering to the intestinal mucosal surface as members of the resident flora that are not easily detectable in stool, most likely representative of a diet-influenced transient microbiota. This first comparative study on feces and LL samples for the study of the human gut microbiome demonstrates that the use of both types of sample matrices may represent a possible choice to obtain a more complete view of the human gut microbiota in response to different biological and clinical questions.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S776-S777
Author(s):  
Angelico Mendy ◽  
Kitty Tierney ◽  
Tara Mink ◽  
Walaa Hussein ◽  
Peter Monaco ◽  
...  

Abstract Background Length of stay is not only an indicator of how successful a hospitalized patient’s treatment and recovery is, but is also an indicator of fiscal costs to the hospital. Hematopoietic stem cell transplants (HSCT) patients typically experience extended hospital admissions that can vary significantly patient to patient with hospital discharge dependent upon a recovered white blood cell count. Recent literature suggests a gut microbial influence on hematopoiesis. We sought to explore potential associations between gut microbiome diversity and the length of stay in patients undergoing HSCT in the inpatient setting. Methods Within two healthcare systems, we identified patients who would receive conditioning chemotherapy and subsequent HSCT in the inpatient setting. Pre-chemotherapy stool was collected, sequenced with shotgun metagenomics, and analyzed for gut microbial diversity using Inverse-Simpson index. The length of admission or length of stay during their transplant process was recorded. We assessed whether there was an association with gut microbial diversity and length of stay. Results 24 patients we evaluated for diversity and length of stay. There was no significant correlation between age or gender and length of stay. Significant difference in length of stay was seen between allogenic vs autogenic transplants (p value ≤0.01). Within the 24 patients, lengths of stay ranged from 8 to 36 days with a mean average of 20.9 days. Gut diversity ranged from 1.8 to 23.9. An overall negative association between length of stay and diversity was seen, though this was determined not statistically significant (p value 0.09). Length of Stay correlation with pre-chemotherapy Gut Microbiome diversity Conclusion Our study showed no significant association between gut microbial diversity and inpatient length of stay during HSCT. Overall, a trend towards increased length of stay in patients with decreased diversity was noted. Additional studies of greater participant size are necessary to confirm or further study these findings. Disclosures All Authors: No reported disclosures


2021 ◽  
Vol 12 ◽  
Author(s):  
Lam T. Khuat ◽  
Logan V. Vick ◽  
Eunju Choi ◽  
Cordelia Dunai ◽  
Alexander A. Merleev ◽  
...  

The efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by the occurrence of acute and chronic graft-versus-host disease (GVHD). We have recently demonstrated that obesity results in exacerbated acute gastrointestinal GVHD in both mouse models and clinical outcomes due to increased pro-inflammatory cytokine responses and microbiota alterations. We therefore wanted to delineate the role of the various parameters in obesity, adiposity, effects of high-fat (HF) diet, and the role of microbiome on GVHD pathogenesis, by taking advantage of a mouse strain resistant to diet-induced obesity (DIO). Female BALB/c mice are resistant to DIO phenotype with approximately 50% becoming DIO under HF diets. The DIO-susceptible recipients rapidly succumb to acute gut GVHD, whereas the DIO-resistant recipient littermates, which do not become obese, are partially protected from GVHD, indicating that being on HF diet alone contributes to but is not the primary driver of GVHD. Microbiome assessment revealed restricted diversity in both cohorts of mice, but coprophagy normalizes the microbiota in mice housed together. We then individually housed DIO-resistant, DIO-susceptible, and lean control mice. Notably, each of the individually housed groups demonstrates marked restricted diversity that has been shown to occur from the stress of single housing. Despite the restricted microbiome diversity, the GVHD pathogenesis profile remains consistent in the group-housed mice, with the lean control single-housed mice exhibiting no acute GVHD and DIO-resistant recipients showing again partial protection. These results demonstrate that the deleterious effects of obesity on acute gut GVHD are critically dependent on adiposity with the HF diet also playing a lesser role, and the microbiome alterations with obesity instead appear to fuel ongoing acute GVHD processes.


2019 ◽  
Vol 97 (Supplement_2) ◽  
pp. 48-48
Author(s):  
Xiaofan Wang ◽  
Tsung Cheng Tsai ◽  
Charles V Maxwell ◽  
Jiangchao Zhao

Abstract Despite the recent advances in the swine gut microbiomes during different growth stages, a comprehensive longitudinal study of the lifelong dynamics of the swine gut microbiome is lacking. To fill this gap of knowledge, we selected seventeen piglets (PIC29*380) that were born on the same date from three sows. We collected a total of 274 rectal swabs during lactation (d 0, 11, 20), nursery (d 27, 33, 41, 50, 61), growing (d 76, 90, 104, 116), and finishing (d 130, 146, 159, and 174) stages. Samples were extracted using the Powersoil DNA isolation kit (Qiagen, Hilden, Germany) and sequenced with an Illumina Miseq sequencer targeting the V4 region of the 16 S rRNA gene. Sequences were analyzed with the Deblur algorithm in the QIIME2 package. In general, alpha diversity including community richness (e.g., number of observed features, Chao1) and diversity (e.g., Shannon Index) showed an overall trend of increasing from lactation to the finishing stage (P < 0.01). Gradual and significant changes in community structures were also observed along the four growth stages (ANOSIM, R = 0.66; P < 0.01). Non-parametric permutational multivariate analysis of variance shows that main factors driving the lifelong community dynamics included age and diet. Seventeen phylum members were discovered in the lifelong pig gut microbiome with Firmicutes and Bacteroidetes being the most abundant phyla. LEfSe analysis revealed 63 bacterial features that are stage specific. By using a regressing tree based Random Forest model we identified five bacterial features that are associated with swine growth performance including features 26 (Turicibacteraceae Turicibacter), 27 (Clostridium butyricum), 18 (Clostridiaceae), 19 (Clostridium perfringens) and 4 (Clostridiaceae). Characterization of the lifelong dynamics of 17 healthy pigs from birth to market provides a foundation for gut microbiome studies focusing on swine development, health and growth performance.


Diabetologia ◽  
2021 ◽  
Author(s):  
Semi Zouiouich ◽  
Erikka Loftfield ◽  
Inge Huybrechts ◽  
Vivian Viallon ◽  
Panayiotis Louca ◽  
...  

Abstract Aims/hypothesis The gut microbiome is hypothesised to be related to insulin resistance and other metabolic variables. However, data from population-based studies are limited. We investigated associations between serologic measures of metabolic health and the gut microbiome in the Northern Finland Birth Cohort 1966 (NFBC1966) and the TwinsUK cohort. Methods Among 506 individuals from the NFBC1966 with available faecal microbiome (16S rRNA gene sequence) data, we estimated associations between gut microbiome diversity metrics and serologic levels of HOMA for insulin resistance (HOMA-IR), HbA1c and C-reactive protein (CRP) using multivariable linear regression models adjusted for sex, smoking status and BMI. Associations between gut microbiome diversity measures and HOMA-IR and CRP were replicated in 1140 adult participants from TwinsUK, with available faecal microbiome (16S rRNA gene sequence) data. For both cohorts, we used general linear models with a quasi-Poisson distribution and Microbiome Regression-based Kernel Association Test (MiRKAT) to estimate associations of metabolic variables with alpha- and beta diversity metrics, respectively, and generalised additive models for location scale and shape (GAMLSS) fitted with the zero-inflated beta distribution to identify taxa associated with the metabolic markers. Results In NFBC1966, alpha diversity was lower in individuals with higher HOMA-IR with a mean of 74.4 (95% CI 70.7, 78.3) amplicon sequence variants (ASVs) for the first quartile of HOMA-IR and 66.6 (95% CI 62.9, 70.4) for the fourth quartile of HOMA-IR. Alpha diversity was also lower with higher HbA1c (number of ASVs and Shannon’s diversity, p < 0.001 and p = 0.003, respectively) and higher CRP (number of ASVs, p = 0.025), even after adjustment for BMI and other potential confounders. In TwinsUK, alpha diversity measures were also lower among participants with higher measures of HOMA-IR and CRP. When considering beta diversity measures, we found that microbial community profiles were associated with HOMA-IR in NFBC1966 and TwinsUK, using multivariate MiRKAT models, with binomial deviance dissimilarity p values of <0.001. In GAMLSS models, the relative abundances of individual genera Prevotella and Blautia were associated with HOMA-IR in both cohorts. Conclusions/interpretation Overall, higher levels of HOMA-IR, CRP and HbA1c were associated with lower microbiome diversity in both the NFBC1966 and TwinsUK cohorts, even after adjustment for BMI and other variables. These results from two distinct population-based cohorts provide evidence for an association between metabolic variables and gut microbial diversity. Further experimental and mechanistic insights are now needed to provide understanding of the potential causal mechanisms that may link the gut microbiota with metabolic health. Graphical abstract


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A719-A719
Author(s):  
Shrutii Sarda ◽  
David Merrill ◽  
Heesun Shin ◽  
Anna McGeachy ◽  
Birgit Drews ◽  
...  

BackgroundA low-cost targeted solution to profiling gut microbial diversity is sequencing of the 16S rRNA gene; however, it is often insufficient to gain species level resolution due to high homology across different bacteria. Therefore, we developed a first-of-its-kind targeted sequencing solution that supplements 16S gene targets, with highly species-specific primers for a cohort of 73 bacteria associated with research in diabetes, cancer and its response to immunotherapy, gastrointestinal and auto-immune disorders. This assay performs at 100% sensitivity and specificity for the species-level detection (Ion AmpliSeq Microbiome Health Research Kit: www.thermofisher.com/ngsmicrobiome) of these bacteria and is hence better suited for gut microbiome profiling in the context of the above phenotypes, as compared to other existing solutions.MethodsTo assess the utility of the panel in cancer immunotherapy research, we sequenced DNA from 15 stool samples from subjects with Non-Small Cell Lung Carcinoma (NSCLC) undergoing immunotherapy, and compared their microbiome profiles to 26 healthy stool samples collected internally. With our post-sequencing workflow on Ion Reporter™, we automatically generate a report with taxonomic classifications, sample diversity metrics through QIIME2 integration, and relative abundance visualizations for bacteria across multiple samples.ResultsWe identified significant microbiome composition differences between the healthy samples and cancer/treated samples, as evidenced by (i) a clear separation between the two cohorts based on a beta diversity principal coordinate analysis (PCoA) plot, driven by large abundance changes in Clostridium, Lachnoclostridium, Subdolinigranulum and Oscillibacter (P < 0.05), (ii) grouping into distinct classes based on overall microbiome profiles (Analysis-of-Similarities ANOSIM P = 0.003), and (iii) differences in abundances of specific bacteria with anti-tumor effects1 such as F. prausnitzii (P = 0.02).ConclusionsWe have created a highly multiplexed, sensitive and specific assay for robust characterization of gut microbiota, with compatibility on both (i) the Ion GeneStudio S5™ with a 48-hr sample-to-result turnaround, and (ii) the new Ion Genexus™ System, a fully integrated platform featuring a hands-off, automated sample-to-report workflow that delivers results in a single day. It enables an efficient and affordable means for conducting extensive analyses of the human microbiome having applications in the study of phenotypic variability, and the potential relationship to disease.For research use only. Not for use in diagnostic procedures.ReferenceMa J, Sun L, Liu Y. et al. Alter between gut bacteria and blood metabolites and the anti-tumor effects of Faecalibacterium prausnitzii in breast cancer. BMC Microbiol 2020; 20:1–19.


Author(s):  
Yue Shi ◽  
Ziyan Miao ◽  
Jianping Su ◽  
Samuel K. Wasser

AbstractThe maternal gut microbiome can influence and be affected by the substantial physiological changes taking place during the perinatal period. However, little information is known about the changes in the maternal gut microbiome during this period. Tibetan antelope (Pantholops hodgsonii) provide a unique system to address this issue because their summer migration cycle is synchronized with the perinatal period. We used 16S rRNA gene sequencing to generate gut microbiome profiles using fecal samples collected from female migratory Tibetan antelope. We then correlated microbiome diversity with fecal hormone metabolite concentrations of glucocorticoids (GCs) and triiodothyronine (T3) extracted from the same fecal samples. The maternal gut microbiome of Tibetan antelope was dominated by Firmicutes and Bacteroidetes. There was a clear separation in gut microbial composition by female reproductive states based on both hierarchical clustering and PCoA analyses. The shift in the maternal gut microbiome likely reflects the metabolic and immune system dynamics during the perinatal period. Overall, the microbiome diversity was higher in the late pregnancy compared to the postpartum period. The negative association between T3 and microbiome diversity may be moderated by the shift of reproductive states since the correlations disappeared when considering each reproductive state separately. Integrating the microbiome dimension, migration pattern and reproduction may have direct conservation implications as by establishing a baseline of the physiological changes during the migration/perinatal period, we can have a better understanding of the impacts of increasing human activities on the Tibetan Plateau on the reproductive health of Tibetan antelope.


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