scholarly journals Diversity and Richness Analysis of the Oral and Gastrointestinal Microbiome during Autologous Transplantation for Multiple Myeloma: Results of a Prospective Pilot Study and Correlation with Transplant Outcomes

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4627-4627
Author(s):  
Najla H El Jurdi ◽  
Ali Filali ◽  
Iman Salem ◽  
Mauricio Retuerto ◽  
Nina Dambrosio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Pilot Study ◽  
Microbial Diversity ◽  
Bacterial Diversity ◽  
Statistical Significance ◽  
R Package ◽  
Advisory Board ◽  
Gastrointestinal Microbiome ◽  
Fecal Samples ◽  
Genus Richness

Abstract Background The human microbiome has been associated with allogeneic hematopoietic cell transplantation (HCT) outcomes, namely infections, graft-versus-host disease and relapse. There are no studies describing the longitudinal changes in the oral or gastrointestinal microbiome in the setting of autologous HCT. We conducted a prospective study to describe the changes in microbial diversity in patients undergoing HCT for multiple myeloma (MM), and whether these correlate with HCT outcomes and/or toxicities. Methods Samples were collected from 15 MM patients on admission (baseline, T-2), during marrow aplasia (T+7) and after engraftment (T+30) (Table 1- summarizes baseline characteristics). We evaluated the bacterial and fungal microbiome of 15 patients using Ion-Torrent PGM workflow. The amplicons generated from the 16s rRNA and the ITS genes were sequenced for bacterial and fungal identification, respectively. Sequencing reads were clustered into operational taxonomic units (OTUs, 3% distance) and taxonomically classified via Qiime bioinformatics pipeline. Diversity was calculated using Shannon diversity index and richness using the R package 'vegan'. Longitudinal analysis was performed using all pairwise Multiple Comparison of Mean Ranks as implemented PMCMR plus R package, employing Kruskal & Wallis test followed by Bonferroni-Dunn post-hoc adjustment. Results Diversity and richness of the oral mycobiome decreased at T+7 compared to pre-transplant levels with further decrease noted at T+30, without reaching significance. Fecal mycobiome diversity and richness decreased from baseline to T+7 meeting statistical significance for diversity (T-2 vs T+7, p=0.05) and richness trended towards significance (p=0.06) with a further decrease noted at T+30. The temporal changes in bacterial diversity and richness in both oral and fecal samples did not reach statistical significance. (Figure1- Box and whisker plots of diversity and richness of the bacteriome and mycobiome at the genus levels from oral rinse and fecal samples) In fecal samples, bacterial diversity noted at T+7 during count nadir was associated with the severity of diarrhea experienced after myeloablation, with lower diversity correlating with more severe diarrhea (p= 0.03). Anaerobic targeting antibiotic exposure on or before T+7 affected both the genus diversity and richness at T+7 (p=0.015 and p=0.014, respectively). The bacterial genus richness at baseline (p=0.03) as well as the diversity and richness noted at T+7 (p=0.01) was associated with the development of fever on or after T+7. For the oral mycobiome, exposure to anaerobic depleting antibiotics correlated with genus richness in T+30 samples (p=0.04). There was a trend towards significance between the diversity of fecal samples at baseline and the development of nausea post transplant, such that higher diversity was associated with lower incidence/severity of nausea (p=0.06). Conclusion and Future Directions While acknowledging the limitation inherent in the small sample size of this pilot study, our results highlight several aspects of the longitudinal changes in the microbiome during HCT. Oral and lower gastrointestinal microbial diversity and richness is altered during HCT with trends significantly different between the oral and fecal bacteriome and mycobiome. This change is likely multifactorial owing to the conditioning regimen, antimicrobial exposure and immune dysregulation. Our data suggest a possible correlation between exposure to anaerobic organism depleting antimicrobials and these changes in microbial diversity and richness at the genus level. Baseline microbial diversity and richness as well as changes coinciding with marrow aplasia could correlate with the incidence and severity of transplant related toxicities. Amifostine was used as a cytoprotectant before high dose melphalan for our patients. The effect of this organic thiophosphate on the microbiota is unclear and it would be of interest to compare matched patient samples to explore the effect of this cytoprotectant on the microbiota. Further studies conducted on a larger scale and incorporating metabolomics and proteomics will help elucidate the interactions between the host and the microbiome and their effect on short term and long term transplantation outcomes as well as toxicities. Disclosures Lazarus: Pluristem Ltd.: Consultancy. Caimi:Celgene: Speakers Bureau; Kite Pharma: Other: Advisory Board Participation; Kite Pharma: Other: Advisory Board Participation; Genentech: Other: Advisory Board PArticipation, Research Funding. Malek:Janssen: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau.

scholarly journals Snapshot on a Pilot Metagenomic Study for the Appraisal of Gut Microbial Diversity in Mice, Cat, and Man

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Coline Plé ◽  
Louise-Eva Vandenborght ◽  
Nathalie Adele-Dit-Renseville ◽  
Jérôme Breton ◽  
Catherine Daniel ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Microbial Diversity ◽  
Human Subject ◽  
Therapeutic Interventions ◽  
Gastrointestinal Microbiome ◽  
Fecal Samples ◽  
Time Points ◽  
Metagenomic Study ◽  
Host Physiology ◽  
Substantial Interest

Gut microbiota plays a key role in the maintenance of homeostasis and host physiology, comprising development, metabolism, and immunity. Profiling the composition and the gastrointestinal microbiome with a reliable methodology is of substantial interest to yield new insights into the pathogenesis of many diseases as well as defining new prophylactic and therapeutic interventions. Here, we briefly present our methodology applied to fecal samples from mice and then further extended to the samples from a cat and a single human subject at 4 different time points as examples to illustrate the methodological strengths. Both interindividual and time-related variations are demonstrated and discussed.

scholarly journals Gastrointestinal Microbiome and Mycobiome Changes during Autologous Transplantation for Multiple Myeloma: Results of a Prospective Pilot Study

2019 ◽  
Vol 25 (8) ◽  
pp. 1511-1519 ◽  
Author(s):  
Najla El Jurdi ◽  
Ali Filali-Mouhim ◽  
Iman Salem ◽  
Mauricio Retuerto ◽  
Nina Margaret Dambrosio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Pilot Study ◽  
Autologous Transplantation ◽  
Gastrointestinal Microbiome ◽  
Prospective Pilot Study

scholarly journals Analysis of Intestinal Microbiome in Multiple Myeloma Reveals Progressive Dysbiosis Compared to MGUS and Healthy Individuals

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3076-3076
Author(s):  
Crystal Antoine Pepeljugoski ◽  
Gareth Morgan ◽  
Marc Braunstein
Keyword(s):  
Multiple Myeloma ◽  
Microbial Diversity ◽  
Research Funding ◽  
Advisory Board ◽  
Intestinal Microbiome ◽  
Rrna Gene ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Genus Level ◽  
Advisory Boards

Background: In addition to acquired genetic changes in neoplastic plasma cells, progression of MGUS to multiple myeloma (MM) is mediated by changes in the proportion of dominant subclones whose expansion is driven by their interaction with the immune microenvironment. Experiments in mouse models of MM have identified a significant contribution to the microenvironment mediated via the gut microbiome and IL-17 responses (Calcinotto et al. Nat Commun 2018;(9)4832:1-7). Despite these preclinical studies, little is known about the composition of the human microbiome in MM at diagnosis, and we hypothesize that it is abnormal and can serve as an axis for immune dysregulation and selection of clonal B cells. In this study we analyzed gut microbial diversity in patients with MGUS and MM and compared these to healthy individuals. Methods: Stool samples were obtained from 10 untreated MGUS and 10 MM patients with ECOG performance status 0-2. Exclusion criteria included those with prior anti-myeloma therapy, primary gastrointestinal disorders, or transient gastrointestinal processes or antibiotic use within the past 3 months. Healthy volunteers from the same geographic region served as controls. 16s rRNA gene sequencing was performed on fecal samples obtained with uBiome Explorer kits processed using Illumina NextSeq500. Qualitative analyses included determination of genera-level operational taxonomic units compared to an established healthy reference range and quantitative assessments of microbial diversity. Cluster analysis was performed using ClustVis (http://biit.cs.ut.ee/clustvis). Results: The mean age at sampling was 74 years for MGUS and 71 for MM. Revised ISS stages I, II, and III for MM patients were 14%, 44%, and 42%, respectively. Median microbial diversity indices showed 84% in MM (range 38-96%), 85% in MGUS (range 42-93%), and 50% in healthy controls (range 23-89%). Supervised clustering of genus-level microbial sequences distinguished specific microbiota separating MM patients from MGUS and healthy controls (Figure). Odoribacter and Lactobacillus were the most enriched genera in MM compared to healthy, conversely Blautia and Faecalibacterium were most reduced. When comparing MM to MGUS, Kluyvera and Bacteroides were found to be most highly represented in MM, whereas Blautia and Parabacteroides showed the greatest decrease compared to MGUS. Data from a MM patient initially enrolled at diagnosis and resampled 4 months after achieving a partial response to induction with VCD showed a decrease in enrichment of Odoribacter from 12.2 to 2.1% as well as Bacteroides from 21.8 to 10.3%. Conclusions: This study identifies distinct changes in the intestinal microbiota that distinguish individuals with MM from its precursor and healthy controls. This is the first time such changes have been identified in untreated MM patients, and some of the genera identified here, such as Faecalibacteria, have been shown to be similarly altered in recent reports of MM patients with persistently active disease despite treatment (Pianko et al. Blood Advances 2019;(3)13:2040-2044). These preliminary studies reveal distinct genus-level differences that exist between MM and MGUS, suggesting increasing dysbiosis with progression to MGUS and MM. We are currently extending these studies to include sequential sampling of additional patients following response to induction chemotherapy. These results provide a rationale for further studying the pathogenic impact of the intestinal microbiome on dysregulation of the MM microenvironment. Figure Disclosures Morgan: Amgen, Roche, Abbvie, Takeda, Celgene, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Other: research grant, Research Funding. Braunstein:Celgene: Consultancy, Other: Advisory Boards; Amgen: Consultancy, Other: Advisory Board; AstraZeneca: Consultancy, Other: Advisory Board; Janssen: Consultancy, Other: Advisory Board, Research Funding; Verastem: Consultancy, Other: Advisory Board; Takeda: Consultancy, Other: Advisory Boards.

scholarly journals HLA-DPA1 gene is a potential predictor with prognostic values in multiple myeloma

2020 ◽  
Author(s):  
Jie Yang ◽  
Fei Wang ◽  
Baoan Chen
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Statistical Significance ◽  
Maximal Clique ◽  
R Package ◽  
Gene Expression Omnibus ◽  
Hub Genes ◽  
Hub Gene ◽  
Regulated Expression ◽  
Hematological Tumor

Abstract Background: Multiple myeloma (MM) is an incurable hematological tumor, which is closely related to hypoxic bone marrow microenvironment. However, the underlying mechanisms are still far from fully understood. We took integrated bioinformatics analysis with expression profile GSE110113 downloaded from National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) database, and screened out major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1) as a hub gene related to hypoxia in MM.Methods: Differentially expressed genes (DEGs) were filtrated with R package “limma”. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed using “clusterProfiler” package in R. Then, protein-protein interaction (PPI) network was established. Hub genes were screened out according to Maximal Clique Centrality (MCC). PrognoScan evaluated all the significant hub genes for survival analysis. ScanGEO was used for visualization of gene expression in different clinical studies. P and Cox p value < 0.05 was considered to be statistical significance.Results: HLA-DPA1 was finally picked out as a hub gene in MM related to hypoxia. MM patients with down-regulated expression of HLA-DPA1 has statistically significantly shorter disease specific survival (DSS) (COX p = 0.005411). Based on the clinical data of GSE47552 dataset, HLA-DPA1 expression showed significantly lower in MM patients than that in healthy donors (HDs) (p = 0.017).Conclusion: We identified HLA-DPA1 as a hub gene in MM related to hypoxia. HLA-DPA1 down-regulated expression was associated with MM patients’ poor outcome. Further functional and mechanistic studies are need to investigate HLA-DPA1 as potential therapeutic target.

scholarly journals HLA-DPA1 gene is a potential predictor with prognostic values in multiple myeloma

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jie Yang ◽  
Fei Wang ◽  
Baoan Chen
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Statistical Significance ◽  
Maximal Clique ◽  
R Package ◽  
Gene Expression Omnibus ◽  
Hub Genes ◽  
Hub Gene ◽  
Regulated Expression ◽  
Hematological Tumor

Abstract Background Multiple myeloma (MM) is an incurable hematological tumor, which is closely related to hypoxic bone marrow microenvironment. However, the underlying mechanisms are still far from fully understood. We took integrated bioinformatics analysis with expression profile GSE110113 downloaded from National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) database, and screened out major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1) as a hub gene related to hypoxia in MM. Methods Differentially expressed genes (DEGs) were filtrated with R package “limma”. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed using “clusterProfiler” package in R. Then, protein-protein interaction (PPI) network was established. Hub genes were screened out according to Maximal Clique Centrality (MCC). PrognoScan evaluated all the significant hub genes for survival analysis. ScanGEO was used for visualization of gene expression in different clinical studies. P and Cox p value < 0.05 was considered to be statistical significance. Results HLA-DPA1 was finally picked out as a hub gene in MM related to hypoxia. MM patients with down-regulated expression of HLA-DPA1 has statistically significantly shorter disease specific survival (DSS) (COX p = 0.005411). Based on the clinical data of GSE47552 dataset, HLA-DPA1 expression showed significantly lower in MM patients than that in healthy donors (HDs) (p = 0.017). Conclusion We identified HLA-DPA1 as a hub gene in MM related to hypoxia. HLA-DPA1 down-regulated expression was associated with MM patients’ poor outcome. Further functional and mechanistic studies are need to investigate HLA-DPA1 as potential therapeutic target.

scholarly journals Soil microbial inoculation during flood events shapes headwater stream microbial communities and diversity

2021 ◽  
Author(s):  
Florian Caillon ◽  
Katharina Besemer ◽  
Peter Peduzzi ◽  
Jakob Schelker
Keyword(s):  
Microbial Diversity ◽  
Bacterial Diversity ◽  
Soil Water ◽  
Headwater Streams ◽  
High Flow ◽  
Low Flow ◽  
Flood Events ◽  
Flow Conditions ◽  
Soil Microbial ◽  
Microbial Inoculation

AbstractFlood events are now recognized as potentially important occasions for the transfer of soil microbes to stream ecosystems. Yet, little is known about these “dynamic pulses of microbial life” for stream bacterial community composition (BCC) and diversity. In this study, we explored the potential alteration of stream BCC by soil inoculation during high flow events in six pre-alpine first order streams and the larger Oberer Seebach. During 1 year, we compared variations of BCC in soil water, stream water and in benthic biofilms at different flow conditions (low to intermediate flows versus high flow). Bacterial diversity was lowest in biofilms, followed by soils and highest in headwater streams and the Oberer Seebach. In headwater streams, bacterial diversity was significantly higher during high flow, as compared to low flow (Shannon diversity: 7.6 versus 7.9 at low versus high flow, respectively, p < 0.001). Approximately 70% of the bacterial operational taxonomic units (OTUs) from streams and stream biofilms were the same as in soil water, while in the latter one third of the OTUs were specific to high flow conditions. These soil high-flow OTUs were also found in streams and biofilms at other times of the year. These results demonstrate the relevance of floods in generating short and reoccurring inoculation events for flowing waters. Moreover, they show that soil microbial inoculation during high flow enhances microbial diversity and shapes fluvial BCC even during low flow. Hence, soil microbial inoculation during floods could act as a previously overlooked driver of microbial diversity in headwater streams.

scholarly journals Busulfan plus melphalan versus melphalan alone conditioning regimen after bortezomib based triplet induction chemotherapy for patients with newly diagnosed multiple myeloma

2021 ◽  
Vol 12 ◽  
pp. 204062072110129
Author(s):  
Songyi Park ◽  
Dong-Yeop Shin ◽  
Junshik Hong ◽  
Inho Kim ◽  
Youngil Koh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Chemotherapy ◽  
Statistical Significance ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
High Dose ◽  
Newly Diagnosed ◽  
Cell Engraftment ◽  
The Difference ◽  
High Dose Melphalan

Background: High dose melphalan (HDMEL) is considered the standard conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients. Recent studies showed superiority of busulfan plus melphalan (BUMEL) compared to HDMEL as a conditioning regimen. We compared the efficacy of HDMEL and BUMEL in newly diagnosed Asian MM patients, who are often underrepresented. Methods: This is a single-center, retrospective study including MM patients who underwent ASCT after bortezomib-thalidomide-dexamethasone (VTD) triplet induction chemotherapy between January 2015 and August 2019. Result: In the end, 79 patients in the HDMEL group were compared to 31 patients in the BUMEL group. There were no differences between the two groups with regards to sex, age at ASCT, risk group, and stage. The HDMEL group showed better response to pre-transplant VTD compared to BUMEL, but after ASCT the BUMEL group showed better overall response. In terms of progression-free survival (PFS), although BUMEL showed trends towards better PFS regardless of pre-transplant status and age, the difference did not reach statistical significance. The BUMEL group more often experienced mucositis related to chemotherapy, but there was no difference between the two groups with regards to hospitalization days, cell engraftment, and infection rates. Conclusion: BUMEL conditioning deserves attention as the alternative option to HDMEL for newly diagnosed MM patients, even in the era of triplet induction chemotherapy. Specifically, patients achieving very good partial response (VGPR) or better response with triplet induction chemotherapy might benefit the most from BUMEL conditioning. Tailored conditioning regimen, based on patient’s response to induction chemotherapy and co-morbidities, can lead to better treatment outcomes.

scholarly journals Gamma entrainment frequency affects mood, memory and cognition: an exploratory pilot study

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Ryan L. S. Sharpe ◽  
Mufti Mahmud ◽  
M. Shamim Kaiser ◽  
Jianhui Chen
Keyword(s):  
Pilot Study ◽  
Correlation Analysis ◽  
Negative Correlation ◽  
Cognitive Abilities ◽  
Statistical Significance ◽  
Assessment Scores ◽  
Frequency Group ◽  
Before And After ◽  
Mood Score ◽  
40 Hz

AbstractHere we provide evidence with an exploratory pilot study that through the use of a Gamma 40 Hz entrainment frequency, mood, memory and cognition can be improved with respect to a 9-participant cohort. Participants constituted towards three binaural entrainment frequency groups: the 40 Hz, 25 Hz and 100 Hz. Participants attended a total of eight entrainment frequency sessions twice over the duration of a 4-week period. Additionally, participants were assessed based on their cognitive abilities, mood as well as memory, where the cognitive and memory assessments occurred before and after a 5-min binaural beat stimulation. The mood assessment scores were collected from sessions 1, 4 and 8, respectively. With respect to the Gamma 40 Hz entrainment frequency population, we observed a mean improvement in cognitive scores, elevating from 75% average to 85% average upon conclusion of the experimentation at weak statistical significance ($$\alpha$$ α = 0.10, p = 0.076). Similarly, memory score improvements at a greater significance ($$\alpha$$ α = 0.05, p = 0.0027) were noted, elevating from an average of 87% to 95%. In pertinence to the mood scores, a negative correlation across all populations were noted, inferring an overall increase in mood due to lower scores correlating with elevated mood. Finally, correlation analysis revealed a stronger R$$^2$$ 2 value (0.9838) within the 40 Hz group between sessions as well as mood score when compared across the entire frequency group cohort.

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