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Microbiome dysbiosis has been associated with adverse outcomes of hematopoietic cell transplantation (HCT). We hypothesized that exposure to high-dose melphalan and antimicrobials in patients undergoing autologous HCT for plasma cell disorders results in oral and gastrointestinal microbial dysbiosis, which in turn is associated with regimen-related toxicities. We conducted a prospective study describing the longitudinal changes in oral and gastrointestinal bacteriome and mycobiome in this patient population. Our findings show that microbiome composition present at baseline is associated with the incidence and severity of post-transplantation nausea, vomiting, and culture-negative neutropenic fever, as well as with the rate of neutrophil engraftment. We also have evidence of an association between the microbial communities at count nadir and the development of regimen-related gastrointestinal toxicities commonly observed after exposure to high-dose melphalan. Although bacteriome diversity largely recovers within 1 month after transplantation, we observed a continuous decrease in oral and gastrointestinal mycobiome diversity, suggesting that the mycobiome requires a longer time to recover compared with the bacteriome.

The mechanisms causing HIV-associated immune activation remain incompletely understood. Alteration of intestinal integrity with subsequent translocation of bacterial products appears to play an important role; however, little is known about the impact of fungal translocation. We assessed the effect of fungal translocation and its association with immune activation in people living with HIV (PLWH) compared with uninfected controls. We measured serum levels of β-D-glucan (BDG) and anti-Saccharomyces cerevisiae antibodies (ASCA) immunoglobulin G (IgG) and immunoglobulin A (IgA) and markers of systemic inflammation and immune activation in virally suppressed PLWH on antiretroviral therapy (ART) and uninfected controls. T-test and Mann–Whitney tests were used to compare markers by HIV status and correlation and regression analyses were used to assess associations of fungal translocation markers with markers of inflammation. One hundred seventy-six participants were included (128 HIV+ and 48 HIV−); 72% male, 65% African American, median age was 50 years, and CD4 was 710 cells/cm(3). Levels of BDG tended to be lower in HIV+ when compared with controls (p = .05). No significant difference in levels of ASCA IgG and IgA was seen between groups (p > .75). There was a significant correlation between BDG and several markers of inflammation and immune activation in PLWH, not seen in uninfected controls. In contrast, no correlations were seen between levels of ASCA IgG and IgA with inflammatory markers. PLWH on ART do not have higher levels of BDG or ASCA when compared with uninfected controls, however, the association found between BDG and several inflammation markers suggests a potential role of fungal translocation in the heightened immune activation seen in treated HIV.

Background: The incidence of type 1 diabetes (T1D) and overweight/obesity is on the rise. Previous studies showed altered gut microbiota in children with T1D where gut microbial differences between obese and lean children without diabetes were reported. The purpose of the study was to characterize the microbial composition of lean and overweight children with T1D at disease onset in comparison to healthy controls. Methods: We enrolled 26 children with T1D at disease onset including 15 lean and 11 overweight T1D and compared them with age, gender and BMI matched 14 lean and 8 overweight controls. Stool swabs were collected and DNA extraction was performed using Qiagen DNA mini kit. Bacterial regions v3, v4 were amplified using 16s primers. Amplicons were cleaned, barcoded, size selected and sequencing was completed on Ion Torrent S5 sequencer. Results: The four most abundant phyla in both groups were Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria. At the genus level, noted significant increase in pro-inflammatory microbes such as Serratia in T1D compared to controls without diabetes (P value= 0.047). Overweight T1D had marked decrease in the beneficial genus Lactobacillus compared to overweight controls. Similar observation was reported when lean T1D was compared to matched lean controls. Although not significant, anti-inflammatory genera like Clostridium had lower relative abundance in obese T1D compared to their lean counterparts. At the species level, when overweight T1D were compared to their matched controls, there was a marked reduction in L. brevis and L. Zeae known for their anti-inflammatory effects (P value = 0.038, 0.046 respectively). Conclusion: Our study showed alterations in the gut microbiome in children with T1D with significant increase in pro-inflammatory microbes. Additionally, being overweight negatively impacted the microbiome. Disclosure S.B. Gowda: None. R.M. Farrell: Research Support; Self; TODAY study. Stock/Shareholder; Self; Dexcom, Inc., Tandem Diabetes Care. S.A. MacLeish: None. I. Salem: None. M.A. Retuerto: None. M.A. Ghannoum: None.

INTRODUCTION AND OBJECTIVE:The risk of infection after penile prosthesis implantation is one of the main concerns for urologic surgeons. Various pre-operative prep methods have been investigated, w...

Emerging data suggest healthy microbiome helps to protect against mucosal injury and inflammation. Dysbiosis results in biofilm formation in the gut which has been shown to be pro-inflammatory. MM patients potentially have significant dysbiosis result of long term corticosteroid use. Our group, previously showed that composition of microbiome presents at the pre-transplant period correlates with rate and degree of post-ASCT GI toxicities, neutropenic fever and neutrophilic engraftment among MM patients. Also, our data suggested a link between microbial communities at the count nadir and GI toxicity after high dose melphalan and ASCT. Mycobiome Supporting Diet (MSD) proposed in this study is designed to restructure the gut microbiome (both bacterial and fungal communities) and support optimal GI tract health. It combines elements from several diets (e.g., Paleo, low-carbohydrate, vegetarian, and Mediterranean) and excludes elements of these diets that have been specifically proven to increase pathogenic fungi in the human gut. Our group examined application of MSD among healthy volunteers between the ages of 30 and 70 who agreed to follow the MSD for 28 days on a prospective trial. At the end of the study period, subjects had a 1.7-fold decrease in the abundance of Proteobacteria (considered a red flag for inflammation), with levels reduced from 38.6% to 23.3% with significantly increased of beneficial species such as Faeclibacterium prausnitzii (up 35.8%) , Bifidobacterium adolescentis (up 61.6%) , Roseburia (up 57.5%) , Lactobacillus (up 77.6%) , and Bacteroides. Furthermore, Pathogenic bacteria decreased significantly, including Escherichia coli (down 74%), Bacteroides fragilis (down 45.3%), and Clostridium (down 55.7%). After the study, all participants with GI symptoms reported moderate or dramatic improvements. Two thirds of the participants who chose to track their weight lost significant weight (between two and 10 pounds) over the testing period. Thirty percent of the participants reported moderate or dramatically improved fatigue and higher energy levels. Given the association between baseline gut dysbiosis and post-transplant GI toxicities and availability of a highly curated diet to optimize the richness and diversity of gut microbiome communities, in this trial (ClinicalTrials.gov Identifier: NCT04685525) we sought to examine the feasibility of MSD diet among MM patients undergoing transplant by assessing its potential effect on decreasing post-transplant GI toxicities. Methods: The primary objective of this study is to evaluate the feasibility of MSD diet using patient's adherence to the MSD diet. The adherence will be assessed 3 times before transplant on days -21, -14 and -7. The MSD diet will deem feasible if at least 80% of patients showed adherence defined by 2 out of 3 assessment marked "more than half a time". With sample size of 40 we will be able to estimate the adherence rate of 80% with 95% confidence interval of +/- 12%. To assess impact of MSD on micro- and mycobiome, a custom pipeline based on Greengenes V13_8 and Unite database V7.2 will be designed for the taxonomic classification of 16SrRNA and ITS sequences, respectively. Downstream data analysis will be performed using Qiime software. Statistical analysis will be performed using the statistical programming language R (version 3.3.0). Change across time in phyla and genus abundance at the community level will be assessed using the non-parametric multivariate distance-based analysis of variance using BC distance for dissimilarity metric along with its standardized binary form. Diversity will be analyzed in an unbiased manner using the Shannon diversity index, a measure of abundance taking into account microbial distribution. Richness will be also assessed, reflecting the microbial counts of the bacterial and fungal communities in each sample. Longitudinal analysis will be performed using all pair wise Multiple Comparison of Mean Ranks as implemented in the PMCMR plus R package version 1.2.0, employing Kruskal & Wallis test followed by Bonferroni-Dunn post-hoc adjustment. P Figure 1 Figure 1. Disclosures Malek: Sanofi: Other: Advisory Board; Bluespark Inc.: Research Funding; Amgen: Honoraria; Cumberland Inc.: Research Funding; Medpacto Inc.: Research Funding; Janssen: Other: Advisory board ; BMS: Honoraria, Research Funding; Takeda: Honoraria. Metheny: Pharmacosmos: Honoraria; Incyte: Speakers Bureau.

// Pranab K. Mukherjee 1,* , Hannah Wang 2, 3, * , Mauricio Retuerto 1 , Huan Zhang 2, 3 , Brian Burkey 4, 7 , Mahmoud A. Ghannoum 1, 7, 8 and Charis Eng 2, 3, 4, 6, 8 1 Center for Medical Mycology, Department of Dermatology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA 2 Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA 3 Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA 4 Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA 5 Section of Head and Neck Surgery and Oncology, Head and Neck Institute, Cleveland Clinic, Cleveland, OH, USA 6 Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA 7 Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA 8 Germline High Risk Cancer Focus Group, CASE Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA * Contributed equally to the work and should be viewed as joint first authors Correspondence to: Charis Eng, email: engc@ccf.org Mahmoud A. Ghannoum, email: mag3@case.edu Keywords: microbiome; metagenomics; head and neck squamous cell carcinoma; lingual carcinomas Received: June 08, 2017 Accepted: September 08, 2017 Published: October 19, 2017 ABSTRACT Squamous cell carcinoma of the oral (mobile) tongue (OMTC), a non-human papilloma virus-associated oral cancer, is rapidly increasing without clear etiology. Poor oral hygiene has been associated with oral cancers, suggesting that oral bacteriome (bacterial community) and mycobiome (fungal community) could play a role. While the bacteriome is increasingly recognized as an active participant in health, the role of the mycobiome has not been studied in OMTC. Tissue DNA was extracted from 39 paired tumor and adjacent normal tissues from patients with OMTC. Microbiome profiling, principal coordinate, and dissimilarity index analyses showed bacterial diversity and richness, and fungal richness, were significantly reduced in tumor tissue (TT) compared to their matched non-tumor tissues (NTT, P

We conducted a prospective study to determine the longitudinal microbial profile in patients undergoing HCT for multiple myeloma (MM), and whether changes in microbial composition correlate with HCT outcomes and/or toxicities. Samples were collected from 15 patients at baseline (T-2), during marrow aplasia (T+7) and after engraftment (T+30). Ion-Torrent PGM workflow was used. Amplicons generated from 16s rRNA and the ITS genes were sequenced for bacterial and fungal identification, respectively. Relative abundance, diversity and richness were determined at the phylum and genus levels at each time point, in oral and fecal microbiome. Diversity and richness of the oral mycobiome decreased at T+7 from baseline with further decrease noted at T+30. Fecal mycobiome diversity (T-2 vs T+7, p=0.05) and richness decreased from baseline to T+7, and richness trended towards significance (p=0.06) with further decrease at T+30. In fecal samples, lower bacterial diversity at T+7 associated with more severe diarrhea (p= 0.03). Anaerobic targeting antibiotic exposure on or before T+7 affected the bacterial genus diversity (p=0.015) and richness at T+7 (p=0.014). The bacterial genus richness at baseline (p=0.03) and the diversity/richness at T+7 (p=0.01) were associated with fever development on or after T+7. Exposure to anaerobic depleting antibiotics correlated with oral mycobiome genus richness at T+30 (p=0.04). At the bacterial phylum level, the oral community composition changed at T+30 compared to baseline (Bray-curtis p=0.046) and T+7 (Bray-curtis p=0.025). When examining the changes in the mycobiome composition, test for dissimilarity showed a significant difference in the fecal fungal genus between baseline and T+30 (BrayPA p=0.025). In fecal samples, a higher abundance of Bacteriodetes present at T+7 was associated with the severity of diarrhea experienced (p=0.03). Blautia and Ruminococcus, both belonging to the Firmicutes phylum and Clostridium Class, when detected at T+7 were associated with a higher severity of vomiting (p=0.05). In oral samples, the presence of the genus Glomerella at T+7 was negatively associated with rates of neutrophil engraftment (p=0.03). Our results show that oral and fecal microbiota undergo dynamic changes in diversity, composition and relative abundance during the course of transplantation. Bacterial and fungal microbiota present specifically at count nadir could be important players. The relative abundance of particularly the anaerobic bacterial phyla, Bacteroidetes and Firciumtes during marrow aplasia, correlated with post transplant toxicities. We identified a correlation between exposure to anaerobic organism depleting antimicrobials and changes in genus diversity and richness. Baseline microbial diversity/richness and changes coinciding with marrow aplasia correlate with the incidence and severity of post transplant toxicities.

A prospective exploratory study was conducted to characterize the oral mycobiome at baseline and determine whether changes occur after admission to the intensive care unit (ICU). We found that ICU admission is associated with alterations in the oral mycobiome, including an overall increase in Candida albicans.

Trichophyton rubrum is the leading pathogen that causes long-lasting skin and nail dermatophyte infections. Currently, topical treatment consists of terbinafine for the skin and ciclopirox for the nails, whereas systemic agents, such as oral terbinafine and itraconazole, are also prescribed. These systemic drugs have severe side effects, including liver toxicity. Topical therapies, however, are sometimes ineffective. This led us to investigate alternative treatment options, such as photodynamic therapy (PDT). Although PDT is traditionally recognized as a therapeutic option for treating a wide range of medical conditions, including age-related macular degeneration and malignant cancers, its antimicrobial properties have also received considerable attention. However, the mechanism(s) underlying the susceptibility of dermatophytic fungi to PDT is relatively unknown. As a noninvasive treatment, PDT uses a photosensitizing drug and light, which, in the presence of oxygen, results in cellular destruction. In this study, we investigated the mechanism of cytotoxicity of PDT in vitro using the silicon phthalocyanine (Pc) 4 [SiPc(OSi(CH 3 ) 2 (CH 2 ) 3 N(CH 3 ) 2 )(OH)] in T. rubrum . Confocal microscopy revealed that Pc 4 binds to cytoplasmic organelles, and upon irradiation, reactive oxygen species (ROS) are generated. The impairment of fungal metabolic activities as measured by an XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt) assay indicated that 1.0 μM Pc 4 followed by 670 to 675 nm light at 2.0 J/cm 2 reduced the overall cell survival rate, which was substantiated by a dry weight assay. In addition, we found that this therapeutic approach is effective against terbinafine-sensitive (24602) and terbinafine-resistant (MRL666) strains. These data suggest that Pc 4-PDT may have utility as a treatment for dermatophytosis.

Crohn’s disease (CD) results from a complex interplay between host genetic factors and endogenous microbial communities. In the current study, we used Ion Torrent sequencing to characterize the gut bacterial microbiota (bacteriome) and fungal community (mycobiome) in patients with CD and their nondiseased first-degree relatives (NCDR) in 9 familial clusters living in northern France-Belgium and in healthy individuals from 4 families living in the same area (non-CD unrelated [NCDU]). Principal component, diversity, and abundance analyses were conducted, and CD-associated inter- and intrakingdom microbial correlations were determined. Significant microbial interactions were identified and validated using single- and mixed-species biofilms. CD and NCDR groups clustered together in the mycobiome but not in the bacteriome. Microbiotas of familial (CD and NCDR) samples were distinct from those of nonfamilial (NCDU) samples. The abundance of Serratia marcescens and Escherichia coli was elevated in CD patients, while that of beneficial bacteria was decreased. The abundance of the fungus Candida tropicalis was significantly higher in CD than in NCDR (P = 0.003) samples and positively correlated with levels of anti-Saccharomyces cerevisiae antibodies (ASCA). The abundance of C. tropicalis was positively correlated with S. marcescens and E. coli, suggesting that these organisms interact in the gut. The mass and thickness of triple-species (C. tropicalis plus S. marcescens plus E. coli) biofilm were significantly greater than those of single- and double-species biofilms. C. tropicalis biofilms comprised blastospores, while double- and triple-species biofilms were enriched in hyphae. S. marcescens used fimbriae to coaggregate or attach with C. tropicalis/E. coli, while E. coli was closely apposed with C. tropicalis. Specific interkingdom microbial interactions may be key determinants in CD., IMPORTANCE Here, we characterized the gut bacterial microbiota (bacteriome) and fungal community (mycobiome) in multiplex families with CD and healthy relatives and defined the microbial interactions leading to dysbiosis in CD. We identified fungal (Candida tropicalis) and bacterial (Serratia marcescens and Escherichia coli) species that are associated with CD dysbiosis. Additionally, we found that the level of anti-Saccharomyces cerevisiae antibodies (ASCA; a known CD biomarker) was associated with the abundance of C. tropicalis. We also identified positive interkingdom correlations between C. tropicalis, E. coli, and S. marcescens in CD patients and validated these correlations using in vitro biofilms. These results provide insight into the roles of bacteria and fungi in CD and may lead to the development of novel treatment approaches and diagnostic assays.

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.

Background The human microbiome has been associated with allogeneic hematopoietic cell transplantation (HCT) outcomes. To date, 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 determine the longitudinal microbial profile in patients undergoing HCT for multiple myeloma (MM), and whether changes in microbial abundance 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. Statistical analysis was performed using the statistical programming language R. Multivariate distance based association between communities and outcome was performed using the Adonis function as implemented in the R package vegan using Bray-curtis dissimilarities distances with and without presence/absence standardization (BrayPA). Non-parametric Spearman correlation and wilcoxon rank-sum test were used for association with continuous outcome and binary outcome respectively. Results Relative abundance was determined at the phylum and genus levels across each time point, in the oral and fecal microbiome, both bacterial and fungal. At the bacterial phylum level, the oral bacterial community composition significantly changed at T+30 compared to baseline (Bray-curtis, p=0.046) and T+7 (Bray-curtis, p=0.025). When examining the changes in the mycobiome composition, test for dissimilarity showed a significant difference in the fecal fungal genus between baseline and T+30 (BrayPA, p=0.025). No other statistically significant differences were noted. Next, we correlated the microbial community (Table 2) and individual composition with outcome and transplant related toxicity, the later will be reported here. In fecal samples, the bacterial phylum Bacteriodetes present at T+7 was associated with the development and severity of diarrhea, such that patients with higher abundance of Bacteroidetes experienced lower gastrointestinal toxicity (pAdj=0.03). Additionally, the 2 genera Blautia and Ruminococcus, both belonging to the Firmicutes phylum and Clostridium Class, when detected at T+7 were associated with a higher development and severity of vomiting after exposure to high dose melphan (pAdj=0.05 for both respectively). In oral samples, the presence of the genus Glomerella at T+7 was negatively associated with rates of neutrophil engraftment (pAdj=0.03). Conclusion and Future Directions While acknowledging the limitation inherent in the small sample size, our results show that oral and fecal microbiota undergo dynamic changes in their diversity (Abstract ID 120038), composition and relative abundance during the course of transplantation. This change is likely multifactorial owing to the conditioning regimen, antimicrobial exposure and immune dysregulation. Our data suggest the bacterial and fungal microbiota present specifically at count nadir could be important players in this population of patients. Interestingly, the relative abundance of particularly the anaerobic bacterial phyla, Bacteroidetes and Firciumtes (Blautia and Ruminococcus) during marrow aplasia, correlated with transplant related toxicities in our cohort. This could further contribute to our knowledge of the role anaerobic organisms play in HCT outcomes, in accordance to what has been described in the allogeneic HCT literature. 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 warrants future investigations. 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. Malek:Amgen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau.